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Principal developer of Biological Bodyguards
Betty Brown, MS
Contributors to Biological Bodyguards
James “Maxx” Andersen, BFA
Lenis Chen, MEd
Cathy Fryar, MEd
Archana Gowda, BA
Dana Haine, MS
Jennifer Murphy, MA
Grant Parkins, MS
Lisa Pierce, MEd
Joy M. Salyers, MA
Amber Vogel, PhD
Jane Wright, MEd, Head of Revision TeamJohn Zhu, BA
Consultants during the development of Biological Bodyguards
Walter E. “Skip” Bollenbacher, PhD
Christine Muth, PhD
Brian Rybarczyk, PhD
Jory Weintraub, PhD

We also wish to acknowledge the model provided by CityLab’s In Search of the Body’s Antibodies(Boston University, 1993) in the early stages of our development of Biological Bodyguards.
DESTINY (http://www.destiny.unc.edu) is the University of North Carolina at Chapel Hill’s Traveling
Science Learning Program. DESTINY is a multi-faceted pre-college education initiative that seeks toempower teachers, schools, and communities to transform science learning environments. DESTINY
has been supported in part by the State of North Carolina; grants from GlaxoSmithKline, the Howard
Hughes Medical Institute, and the National Aeronautics and Space Administration; and a Science Education
Partnership Award from the National Center for Research Resources, part of the National Institutes of Health.
Additional support has come from Bio-Rad, IBM, Medtronic, and New England BioLabs.

© 2006 DESTINY. DESTINY grants teachers permission to reproduce curriculum materials from thisnotebook for classroom use only, without alteration, provided all copies contain the following statement: “© 2006 DESTINY. This work is reproduced with the permission of DESTINY, UNC-Chapel Hill’s
Traveling Science Learning Program. No other use is permitted without the express prior written permission of DESTINY. For permission, contact DESTINY, UNC-Chapel Hill’s Traveling Science Learning Program, CB# 7448, Morehead Planetarium and Science Center Annex, UNC-Chapel Hill, Chapel Hill, NC 27599-7448.”

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This Biological Bodyguards module uses:

Bio-Rad Explorer
ELISA Immuno Explorer Kit
Catalog #1662400EDU
bio-rad.com/ELISAkit
1-800-4BIORAD (1-800-424-6723)



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TABLE OF CONTENTS
KEY TERMS...........................................................5
ALIGNMENTS.......................................................9
The Key Components of the 5E Model....................9North Carolina Standard Course of Study..............10
National Science Education Standards...................16
INTRODUCTION................................................19
Background.............................................................19
The Immune System...............................................19
Key Players.............................................................19
Immunity.................................................................20
The Immune Sequence............................................21
Pre-lab.....................................................................24
Wet Lab...................................................................24
HIV: How It Functions....................................24
The ELISA.......................................................24
Treatments for Common Illnesses...................25
Interdisciplinary Bridges.........................................26
Connection to Other Modules.................................27
HIV Fact Sheet........................................................28
PRE-LAB...............................................................29
Utilizing the 5E Instructional Model......................30
Engagement Activity...............................................31
Disease List with Symptoms...................................32
Exploration Activity, Part 1.....................................34
Exploration Activity, Part 2.....................................37
Exploration Activity, Part 2 Role Play Cards..........38
Explanation/Elaboration Background Information....43
Explanation/Elaboration Activity:
TV Show, Dial in for a Dialogue with a Doc..........50
KEY Explanation/Elaboration Activity:
TV Show, Dial in for Dialogue with a Doc.............51
Evaluation Activity:
The Humoral Response Concept Map....................55
KEY Evaluation Activity:
The Humoral Response Concept Map....................57

Wet Lab Protocol: ELISA Antibody Test................68
Data/Observation Sheet..........................................69
KEY Data/Observation Sheet..................................70
List of Equipment Needed for Wet Lab..................71
POST-LAB.............................................................73
Quiz Game Questions.............................................74
KEY Quiz Game Answers.......................................75
Post-lab Focus Questions........................................76
KEY Answers to Post-lab Focus Questions.............77
Video Comprehension Questions:
An Inside Look: The Flu.........................................78
KEY Answers to Video Comprehension Questions:
An Inside Look: The Flu.........................................79
Homework Assignment...........................................80
ADDITIONAL ACTIVITIES..............................81
Deadly Disease among Us:
Pamphlet on a Disease............................................82
ELISA Additional Lab Activity: The Sensitivity
Range of a Home Pregnancy ELISA Test for
Human Chorionic Gonadotropin (HCG)................83
AIDS: The Effect on the Immune Response...........85
INTERDISCIPLINARY BRIDGES....................89
Follow-up Activity:
Using Drugs? You’re in Trouble.............................90
KEY Answers to Follow-up Activity:
Using Drugs? You’re in Trouble.............................91
Global State of Emergency: Government’s
Role in Curbing the AIDS Crisis............................92
Battling Bioterrorism:
Understanding the Science and Politics..................95
A Discovery-Based Approachto Understanding Clinical Trials...........................100
Germs in the Arts and Humanities........................ 110

WET LAB..............................................................59
Real-World Applications of ELISA:
Enzyme-Linked Immunosorbent Assay..................60
Wet Lab Engagement Activity:
HIV Simulation: Tracking a Disease Outbreak......61
HIV Simulation:
Tracking a Disease Outbreak Class Results............63
Biological Bodyguards Wet Lab.............................64
Focus Questions: ELISA.........................................65
KEY Answers to Focus Questions: ELISA.............66
Explanation of ELISA Test.....................................67

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DESTINY - UNC-CHAPEL HILL - CB# 7448, Morehead Planetarium and Science Center Annex - Chapel Hill, NC 27599-7448 - (919) 843-9036 - www.destiny.unc.edu

KEY TERMS

Clone — a cell or group of cells that are all derived
through cell division from the same parent cell and thus
have identical genetic information.

Acquired immunity — a specific response to specificforeign substances to which the body adapts with multiple exposures; also called adaptive immunity.

Complement — one group of proteins that destroys
bacterial cells.

AIDS — acquired immunodeficiency syndrome, causedby the human immunodeficiency virus (HIV).
Anatomical barriers — natural barriers to infection
such as skin, mucous membranes, ciliated epithelial
cells, tears, and saliva.
Antibody — immunoglobulin protein formed in
response to a challenge of the immune system by aforeign agent. Antibodies bind to specific antigens.
Antigen — any agent that provokes an immune response and is bound specifically by either antibodies or
T cells. Also called immunogen.
Antiserum — blood serum containing antibodies defending against a specific antigen.
Assay — a test to detect the presence and/or concentration of a component, drug, or microorganism in the
blood or other body fluids or tissues; see also ELISA.
Autoimmune disease — disease that results from theimmune system making a mistake and mounting an
immune response against one’s own body; examples are
systemic lupus erythematosus (lupus, SLE), rheumatoid
arthritis, and multiple sclerosis (MS).
Bacteria — a diverse group of organisms whose members are unicellular and prokaryotic. Some members
are deadly parasites.
Bacteriophage — a virus that infects bacteria, also
called a phage; can be used to introduce foreign DNA
into a bacterial genome.
B cells — one type of white blood cell (lymphocyte)
which matures in the bone marrow; once activated,some B cells develop into plasma cells to make antibodies to the antigen and other B cells develop intomemory B cells.

Conjugate — a substance formed by the covalentbonding of two types of molecules such as HRP linked
to an antibody.
Cytokine — any of a group of regulatory proteinssecreted by cells of the immune system, including lymphokines (secreted by lymphocytes), monokines (secreted by macrophages), interferons (secreted by both)and interleukins (secreted by both). Cytokines bind to
receptors on other cells to alter the behavior of cells.
ELISA — enzyme-linked immunosorbent assay, a tool
which utilizes antibodies to detect a particular antigen.
Enzyme — a protein that acts as a biological catalyst.
The molecule that an enzyme acts on is called its substrate; for example, the enzyme horseradish peroxidase
oxidizes its substrate.
Epitope — a specific site on an antigen that is recognized and bound by an antibody.
Genetically modified organism (GMO) — an organism whose genetic material (DNA) has been altered ina way that does not occur naturally by mating or natural
recombination.
HIV — human immunodeficiency virus, the virus thatcauses AIDS (acquired immunodeficiency syndrome).
Horseradish peroxidase (HRP) — an enzyme frequently used to label secondary antibodies.
Humoral response — also known as humoral immune
response, occurs when B cells interact with the antigen,which eventually results in their transformation into
antibody-producing plasma cells.

Cancer — a disease in which the body’s own cells lose
the ability to control growth.

Hydrophobic — nonpolar compounds that are immiscible with water, literally “water fearing.” The side
chains of some amino acids are nonpolar, and hence
protein sequences rich in these amino acids tend tolocate to the interior of the protein in its native state,away from the presence of a solvent.

Chromogenic — substrates that produce a coloredproduct when acted upon by an enzyme.

Immune cells — the cells of the immune system, including lymphocytes (B and T cells) and macrophages.

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Immunocompetent — B cells and T cells that are
fully developed and armed to fight infection. These will
recirculate from blood to lymph to blood.
Immunodeficiency — weakening or defects of theimmune response such that an individual is unable tomount an effective immune response; may have a genetic basis, result from a disease or other health factor,
or be caused by immunosuppressive drugs.
Immunoglobulin (Ig) — general term for all types ofantibodies; in the humoral response, B cells function to
produce antibodies.
Immunology — the study of the immune system—thebodily system that protects the body from foreign
substances, cells, and tissues by producing an immune
response.
Interferon — one of the groups of proteins that alerts
the body to the presence of an antigen; typically a virus
or cancer. An adaptive or inflammatory response isthen activated.
Interleukin — a type of protein released by T cells toactivate immunocompetent B cells to make antibodies
to respond to the antigen.
Innate immunity — the immunity with which a person
is born. Nonspecific host defenses that exist prior to
exposure to an antigen; includes cells such as circulating macrophages that respond to foreign invaders.
Lag time — the length of time (usually several days)
from infection to antibody production.
Leukocyte — a white blood cell. The category
includes lymphocytes, macrophages and other whiteblood cells.
Lymphocyte — type of white blood cell. Componentof the immune system includes T cells (thymus - derived) and B cells (bone marrow-derived).
Lymphokine — proteins released by immunocompetent T cells into the blood stream that activate B cells to
respond to the antigen. An example is interleukin.
Macrophage — a type of white blood cell that binds
and engulfs foreign materials and antigens in a process called phagocytosis; two primary functions are 1)
removing foreign cells and molecules from the blood,and 2) processing antigens and presenting them on theircell surfaces.



Memory B cells — as the activated B cell reproduces,
it will also make memory B cells; these memory B
cells have antigen-binding regions that are identicalto those of the original parent B cell. The memory B
cells persist in the body and the next time the antigen is
encountered, it will be recognized more quickly and the
response will be more vigorous.
Microplate — molded plastic plate consisting of multiple small wells. Usually in a 96-well format.
Multiple Sclerosis — an autoimmune disease that affects the central nervous system.
Opportunistic infections — infections that occur
as a result of deficiencies in the immune system; forexample, diseases like oral candidiasis and tuberculosisthat occur in immunodeficient AIDS patients.
Passive immunity — the acquisition of antibodies froman external source; for example, antibodies passed frommother to infant or certain postexposure vaccines suchas that for rabies. Passive immunity lasts only a few
weeks and does not change with multiple exposures.
Pathogens — organisms that can cause disease. Pathogens include bacteria, viruses, fungi, infectious proteins
called prions, and parasites.
Phage display — a method of producing novel antibodies to specific antigens using recombinant DNA
technology.
Phagocytic barriers — white blood cells with thecapacity to engulf and destroy microbes or antigens.
Phagocytosis — the ingestion and destruction of microorganisms, foreign matter, and debris from damaged cells
by white blood cells (neutrophils and macrophages).
Physiological barriers — conditions within the bodyunder which infectious agents cannot survive including body temperature and pH (as in the acid pH of thestomach).
Plasma cells — cells produced by activated B cells that
release antibodies, which are proteins that bind to theantigen.
Primary antibody — the antibody in an immunoassaythat binds a specific antigen, conferring specificity to
the assay.

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Rheumatoid arthritis — an autoimmune disease thatcauses joint pain.
Secondary antibody — in an immunoassay, the antibody that recognizes and binds the primary antibody,which is from a different species. Secondary antibodies
are frequently labeled with an enzyme for easy detection.
Serum — the clear, sticky fluid obtained when thesolid components (e.g., red and white blood cells) areremoved from whole blood. The plural for serum frommultiple patients or sources is sera.
Substrate — reactant produced by an enzyme-catalyzed reaction. The particular substrate frequently usedin ELISA assays oxidizes to a blue color by the horseradish peroxidase enzyme.
T cells — one type of white blood cell (a lymphocyte)that starts in the bone marrow, enters the bloodstream,and matures in the thymus.
T helper cells — TH cells (which are lymphocytes)
must be activated by specific antigens before they become functional. These cells produce factors needed forthe production of plasma cells and memory B cells.

Vectors — organisms that carry pathogens from one
host to another. Vectors are frequently arthropods (e.g.,ticks and mosquitoes).
Virus — ultramicroscopic infectious agent that replicates itself only within cells of living hosts; many arepathogenic.
Western blotting — a common technique for detecting
proteins. The proteins are separated by electrophoresis
based on size and/or charge.
White blood cell — another term for leukocytes.

SOURCES
BIO-RAD, ELISA Immuno Explorer™ Kit, Catalog#166-2400EDUHBP310 Immunology. Retrieved August 25, 2006, from
SUNY Stony Brook Web site: http://www.path.sunysb.
edu/coursemat/hbp310immun.htm

Vaccination — the process of inducing acquired immunity by deliberately stimulating an immune responsewith a nonpathogenic form of a disease agent. Also
called immunization. The first vaccination used cowpox
to inoculate against smallpox.

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The Key Components of the 5E ModelPHASE
ENGAGEENGAGEENGAGEEXPLOREENGAGEEXPLOREENGAGE...
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WHAT THE TEACHER DOES THAT IS
Consistent with the 5E Model

Inconsistent with the 5E Model• Creates interest• Generates curiosity• Raises questions• Elicits responses that uncover what students knowor think about the concept/subject• Explains concepts• Provides definitions and answers• States conclusions• Provides premature answers to students’ questions• Lectures• Encourages students to work together without direct
instruction from teacher• Observes and listens to students as they interact• Asks probing questions to redirect students’ investigations when necessary• Provides time for students to puzzle through problems• Acts as a consultant for students• Provides answers• Tells or explains how to work through the problem• Tells students they are wrong• Gives information or facts that solve the problem• Leads students step-by-step to a solution• Encourages students to explain concepts and definitions in their own words• Asks for justification (evidence) and clarificationfrom students• Formally provides definitions, explanations, andnew labels• Uses students’ previous experiences as the basis for
explaining concepts• Accepts explanations that have no justification• Neglects to solicit students’ explanations• Introduces unrelated concepts or skills• Expects students to use formal labels, definitions
and explanations provided previously• Encourages students to apply or extend concepts
and skills in new situations• Reminds students of alternative explanations• Refers students to existing data and evidence and asks
“What do you already know?”“Why do you think…?”• Provides definitive answers• Tells students they are wrong• Lectures• Leads students step-by-step to a solution• Explains how to work through the problem• Observes students as they apply new concepts andskills• Assesses students’ knowledge and/or skills• Looks for evidence that students have changed theirthinking or behaviors• Allows students to assess their own learning andgroup process skills• Asks open-ended questions, such as “Why do you
think . . . ?”“What evidence do you have?”“What do
you know about x?”“How would you explain x?”• Tests vocabulary words, terms and isolated facts• Introduces new ideas or concepts• Creates ambiguity• Promotes open-ended discussion unrelated toconcept or skill...
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EXPLAINEVALUATEELABORATEEVALUATEELABORATEEVALUATE
THE 5E’s

EVALUATEEVALUATE
THE 5E’s
THE 5E’s(Trowbridge & Bybee, 1990), adapted by Biological Sciences Curriculum Study
Available online at http://science.education.nih.gov/supplements/nih1/diseases/guide/module3.htm

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THE 5E’s

THE 5E’s2005-06 North Carolina Standard Course of Study for Biology — Grades 9-12*** Highlighted sections are objectives addressed in the Biological Bodyguards module
Strands: Nature of Science, Science as Inquiry, Science and Technology, Science in Personal andSocial Perspectives. The strands provide the context for teaching of the content Goals and Objectives.
Competency Goal 1:
The learner will develop abilities necessary to do and understand scientific inquiry.
Objectives
1.01 Identify biological questions and problems that can be answered through scientific investigations.
1.02 Design and conduct scientific investigations to answer biological questions.
• Create testable hypotheses• Identify variables• Use a control or comparison group when appropriate• Select and use appropriate measurement tools• Collect and record data
• Organize data into charts and graphs• Analyze and interpret data
• Communicate findings
1.03 Formulate and revise scientific explanations and models of biological phenomena using logic and evidence to:• Explain observations• Make inferences and predictions• Explain the relationship between evidence and explanation
1.04 Apply safety procedures in the laboratory and in field studies:• Recognize and avoid potential hazards•Safely manipulate materials and equipment needed for scientific investigations
1.05 Analyze reports of scientific investigations from an informed, scientifically literate viewpoint including
considerations of:• Appropriate sample• Adequacy of experimental controls• Replication of findings•Alternative interpretations of the data
Competency Goal 2:
The learner will develop an understanding of the physical, chemical and cellular basis of life.
Objectives
2.01 Compare and contrast the structure and functions of the following organic molecules:• Carbohydrates• Proteins• Lipids• Nucleic acids
2.02 Investigate and describe the structure and functions of cells including:• Cell organelles• Cell specialization• Communication among cells within an organism.
2.03 Investigate and analyze the cell as a living system including:• Maintenance of homeostasis• Movement of materials into and out of cells• Energy use and release in biochemical reactions

10

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2.04 Investigate and describe the structure and function of enzymes and explain their importance in biologicalsystems.
2.05 Investigate and analyze the bioenergetic reactions:• Aerobic respiration• Anaerobic respiration• Photosynthesis
Competency Goal 3:
The learner will develop an understanding of the continuity of life and the changes of organisms over time.
Objectives
3.01 Analyze the molecular basis of heredity including:• DNA replication• Protein synthesis (transcription, translation)• Gene regulation
3.02 Compare and contrast the characteristics of asexual and sexual reproduction.
3.03 Interpret and predict patterns of inheritance.
• Dominant, recessive and intermediate traits• Multiple alleles• Polygenic inheritance• Sex-linked traits• Independent assortment• Test cross• Pedigrees• Punnett squares
3.04 Assess the impact of advances in genomics on individuals and society.
• Human genome project• Applications of biotechnology
3.05 Examine the development of the theory of evolution by natural selection, including:• Development of the theory• The origin and history of life
• Fossil and biochemical evidence• Mechanisms of evolution• Applications (pesticide and antibiotic resistance)
Competency Goal 4:
The learner will develop an understanding of the unity and diversity of life.
Objectives
4.01 Analyze the classification of organisms according to their evolutionary relationships.
• The historical development and changing nature of classification systems• Similarities and differences between eukaryotic and prokaryotic organisms• Similarities and differences among the eukaryotic kingdoms: protists, fungi, plants, animals• Classify organisms using keys
4.02 Analyze the processes by which organisms representative of the following groups accomplish essential life
functions including:• Unicellular protists, annelid worms, insects, amphibians, mammals, non vascular plants, gymnosperms
and angiosperms• Transport, excretion, respiration, regulation, nutrition, synthesis, reproduction, and growth and development
4.03 Assess, describe and explain adaptations affecting survival and reproductive success.
• Structural adaptations in plants and animals (form to function)• Disease-causing viruses and microorganisms• Co-evolution

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114.04 Analyze and explain the interactive role of internal and external factors in health and disease:• Genetics• Immune response• Nutrition• Parasites• Toxins
4.05 Analyze the broad patterns of animal behavior as adaptations to the environment.
• Innate behavior• Learned behavior• Social behavior
Competency Goal 5:
The learner will develop an understanding of the ecological relationships among organisms.
Objectives
5.01 Investigate and analyze the interrelationships among organisms, populations, communities, and ecosystems.
• Techniques of field ecology• Abiotic and biotic factors• Carrying capacity
5.02 Analyze the flow of energy and the cycling of matter in the ecosystem.
• Relationship of the carbon cycle to photosynthesis and respiration• Trophic levels — direction and efficiency of energy transfer
5.03 Assess human population and its impact on local ecosystems and global environments.
• Historic and potential changes in population• Factors associated with those changes• Climate change• Resource use• Sustainable practices/stewardship2005-06 North Carolina Standard Course of Study for Healthful Living — Grades 9-12*** Highlighted sections are objectives addressed in the Biological Bodyguards module
Strands: Preparatory, Stress Management, Protecting Self/Others, Relationships, Nutrition/Weight Management, Substance Abuse, Personal Fitness, Healthful Lifestyles, Appreciation for Diversity, Social Wellness,
Movement Forms, Fitness and Sport Literacy
Competency Goal 1:
The learner will direct personal health behaviors in accordance with own health status and susceptibility
to major health risks.
Objectives
1.01 Assess own health status.
1.02 Accept responsibility for own health.
1.03 Determine individual control over health risks.
1.04 Compare relationship of health to quality of life.
1.05 Describe the procedures for organ donation, local and state resources, and benefits to society.
1.06 Identify the value for personal outcomes acquired from lifelong learning about health education.

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Competency Goal 2:
The learner will apply skills of stress management to theprevention of serious health risks for self & others.
Objectives
2.01 Develop awareness of own control over stress.
2.02 Replace negative thoughts with positive.
2.03 Associate behaviors with personal, family, and cultural values.
2.04 Cope with losses appropriately.
2.05 Respond to others with empathy.
2.06 Identify symptoms of mental disorders and know where to seek professional assistance.
Competency Goal 3:
The learner will interpret health risks for self and others and corresponding protection measures.
Objectives
3.01 Interpret the importance of various health risks.
3.02 Explain activities taken for disaster preparedness.
3.03 Prioritize own health risks and construct a model health risk behavior self-management plan.
3.04 Identify risk behavior to manage.
3.05 Explain the importance of early detection, including medical examination and self-examination.
3.06 Assess behaviors and decisions as to their likelihood of resulting in infant morbidity and mortality.
3.07 Understand that a mutually faithful monogamous heterosexual relationship in the context of marriage is thebest lifelong means of avoiding sexually transmitted diseases, including HIV/AIDS.
3.08 Refine skills and strategies for remaining or becoming abstinent from sexual intercourse, and avoiding
sexually transmitted diseases, including HIV/AIDS.
3.09 Understand causes, consequences, and prevention of major health risk behaviors for own age group, including the transmission of HIV/AIDS.
Competency Goal 4:
The learner will apply relationship skills to the promotion of health and the prevention of risk.
Objectives
4.01 Analyze problems stemming from unhealthy relationships.
4.02 Implement skills which develop positive relationships.
4.03 Utilize anger management skills.
4.04 Identify resources for managing relationship problems.
4.05 Demonstrate conflict resolution skills.
4.06 Formulate principles for healthful dating relationships.
Competency Goal 5:
The learner will apply behavior management skills to nutrition-related health concerns.
Objectives
5.01 Provide detailed examples of how nutrition and physical activity can reduce the risk for chronic diseases.
5.02 Develop a personal healthful eating plan that incorporates food choices outside the home setting.
5.03 Develop specific eating plans to meet changing nutritional requirements, such as special dietary needs,
athletic training, pregnancy, and food allergies.
5.04 Describe the pharmacological benefits of nutrients such as folic acid.
5.05 Evaluate specific diet plans found in popular magazines and books.
5.06 Design a plan for personal weight management based on a realistic and healthful body image.
5.07 Differentiate between healthful and harmful dietary habits.

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13Competency Goal 6:
The learner will choose not to participate in substance use.
Objectives
6.01 Recognize and seek help for depression.
6.02 Describe the potential effects on others of substance abuse by individuals.
6.03 Analyze motives for and consequences of steroid abuse.
6.04 Access services for dealing with substance abuse problems.
6.05 Explain behavior change strategies used in the treatment of substance abuse.
6.06 Delineate the risks involved in binge drinking.
6.07 Define “Fetal Alcohol Syndrome” and describe how it is prevented.
Competency Goal 7:
The learner will achieve and maintain an acceptable level of health-related fitness.
Objectives
7.01 Recognize and apply safety techniques, practices, and guidelines as related to fitness and nutrition.
7.02 Identify and analyze the principles of cardiovascular and strength development.
7.03 Complete a health related fitness test and assess personal level of physical fitness, including monitoring of
the heart.
7.04 Interpret multiple sets of data in order to determine the best course of action for a healthy personal lifestyle.
7.05 Design and implement a personal activity program that demonstrates the relationship between physicalactivity, nutrition and weight management.
7.06 Recognize the implications of cardiovascular disease on healthy living.
Competency Goal 8:
The learner will exhibit regular physical activity.
Objectives
8.01 Identify resources in the community that can be accessed to maintain regular physical activity.
8.02 Evaluate the benefits of various physical activities.
8.03 Demonstrate and evaluate the importance of regular physical activity and proper diet.
8.04 Use goals and logical steps to develop an action plan to organize resources in order to be physically active.
8.05 Participate regularly in health-enhancing and personally rewarding physical activity outside the physicaleducation class setting.
8.06 Appreciate and value the importance of regular physical activity.
Competency Goal 9:
The learner will demonstrate an understanding and respect fordifferences among people in physical activity settings.
Objectives
9.01 Execute respect for individual differences in physical activity settings.
9.02 Synthesize and evaluate knowledge about the role of physical activity in a diverse society.
9.03 Develop strategies for including persons of diverse backgrounds and abilities in physical activity settings.

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Competency Goal 10:
The learner will demonstrate responsible personal and social behavior in physical activity settings.
Objectives
10.01 Work productively as a member of a team and contribute to the team’s success through the assumption ofa variety of noncompetitive duties.
10.02 Set personal goals for the development of skills, knowledge, and social responsibility, and work independently toward those goals.
10.03 Practice acceptable sportsmanship and fair play behaviors in physical activity settings.
10.04 Apply cooperative social skills to partner and group activities such as dance, outdoor activities, teambuilding, problem solving, and cooperation games.
10.05 Demonstrate leadership in physical activities.
Competency Goal 11:
The learner will participate successfully in a variety of movement forms andgain competence towards lifetime physical activities.
Objectives
11.01 Participate at a competent level in small-sided games in at least one team sport.
11.02 Participate at a competent level in small-sided games in at least one individual or dual sport.
11.03 Participate at a competent level in at least one other movement form such as dance, gymnastics, aquatics,
and outdoor pursuits.
11.04 Engage in various duties as they pertain to games and sport.
Competency Goal 12:
The learner will demonstrate a competent level of physical activity, sport, and fitness literacy.
Objectives
12.01 Exhibit knowledge of concepts in three different activities by officiating, judging, or refereeing.
12.02 Demonstrate competence in basic offensive and defensive strategies or tactics in team, individual, anddual activities.
12.03 Apply rules, biomechanical or movement principles, problem solving and fitness concepts to game andmovement settings.
12.04 Know and apply safe practices in physical activity settings.
12.05 Apply statistical data about personal and group performance to the improvement of game play.

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15Biological Bodyguards
Correlation to the National Science Education Standards
The Teaching Standards
Biological Bodyguards Correlation
Each activity in the module provides short-term objectives for students. Thereis a conceptual flow of activities and help teachers plan a timeline for teaching
the module.
Use of this module helps teachers to update their curriculum in response to
student interest in the topic.

Standard A: Teachers of science plan an inquiry-based science program
for their students. In doing this, teachers• develop a framework of yearlong and short-term goals for students.
• select science content and adapt and design curriculum to meet the interest, knowledge, understanding, abilities, and experiences of students.
• select teaching and assessment strategies that support the development ofstudent understanding and nurture a community of science learners.

The module’s focus is active, collaborative, and inquiry-based.
Student inquiry is encouraged by all activities in the module.
The module promotes discourse among students, and challenges students toaccept responsibility for their own learning by using hands-on, inquiry-based
activities.
The use of the 5E instructional model with collaborative learning is an effective way of responding to diversity in student backgrounds and learning styles.

There are a variety of assessment components provided in the module, such asgroup discussion, data collection, and student writing activity.
Answers are provided to help teachers analyze student feedback.

The answers provided for teachers model respect for diverse ideas, skills, andexperiences of all students.
Students work collaboratively in teams to complete activities in the module.
Discussion activities in this module model the rules of scientific discourse.

16Standard B: Teachers of science guide and facilitate learning. In doing
this, teachers• focus and support inquiries while interacting with students.
• orchestrate discourse among students about scientific ideas.
• challenge students to accept and share responsibility for their own learning.
• recognize and respond to student diversity and encourage all students toparticipate fully in science learning.
• encourage and model the skills of scientific inquiry, as well as the curiosity,
openness to new ideas and data, and skepticism that characterize science.
Standard C: Teachers of science engage in ongoing assessment of theirteaching and of student learning. In doing this, teachers• use multiple methods and systematically gather data about student
understanding and ability.
• analyze assessment data to guide teaching.
Standard E: Teachers of science develop communities of science learners
that reflect the intellectual rigor of scientific inquiry and the attitudes
and social values conducive to science learning. In doing this, teachers• display and demand respect for the diverse ideas, skills, and experiences ofall students.
• structure and facilitate ongoing formal and informal discussion based on ashared understanding of rules of scientific discourse.
• model and emphasize the skills, attitudes, and values of scientific inquiry.

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Biological Bodyguards
Correlation to the National Science Education Standards
The Content Standards
Biological
Bodyguards
activityPre-lab Activities
Wet Lab Activities
Additional Activities:
Convince Your Peers
Classroom guide to
Arousing the Fury of
the Immune System
Additional Activities
Video: The Flu
Immune System Animations

Standard A (Science as Inquiry) : As a result of activities in grades 9-12, all students should develop
1. abilities necessary to do scientific inquiry.
• identify questions and concepts that guide scientific investigations• Use technology and mathematics to improve investigations and communications• Formulate and revise scientific explanations and models using logic and evidence• Recognize and analyze alternative explanations and models• Communicate and defend a scientific argument
2. understanding about scientific inquiry.
Standard C (Life Science): As a result of their activities in grades 9-12, all students should develop understanding of
1. the cell.
• Cells store and use information to guide their functions• Cells can differentiate, and complex multicellular organisms are formed as a highly organized arrangement of differentiated cells

Pre-lab Activities
Additional Activities
Super Bugs: An Evolving
Concern
Additional Activities
Superbugs
Deadly Diseases Among Us

Wet Lab Activities
Post-lab Activities
Additional Activities

2. molecular basis of heredity.
• In all organisms, DNA carries the instructions for specifying organism characteristics• Changes in DNA occur spontaneously at low rates

3. biological evolution.
• Species evolve over timeStandard E (Science and Technology): As a result of activities in grades 9-12, all students should develop understanding of
1. abilities of technological design.
2. science and technology.
• Scientists in different disciplines ask questions, use different methods of investigation, and accept different types of evidence
to support these explanations• Science often advances with the introduction of new technologies• Creativity, imagination, and good knowledge base are all required in the work of science and engineering• Science and technology are pursued for different purposes

Additional Activities
Protecting the Herd
Prepare a pamphlet

Standard F (Science in Personal and Social Perspectives): As a result of activities in grades 9-12, all students should
develop understanding of
1. personal and community health.
5. human-induced hazards.
6. science and technology in local, national and global challenges.

Additional Activities
Benefits of Biomedical
Research

Standard G (History and Nature of Science): As a result of activities in grades 9-12, all students should develop
understanding of
1. science as a human endeavor.
2. nature of scientific knowledge.
3. historical perspectives.

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INTRODUCTION
This module reviews various parts and functions of the immune system, in order to meetthe following objectives:
1. To describe how the body defends
itself against pathogens and antigens;
2. To identify the role of antibodies in the
immune system;
3. To diagram the events of the humoral
and cell-mediated immune responses of
the immune system;
4. To describe the process of conducting
an ELISA test, interpret the results, andrecognize the real-life applications of sucha test for the presence of HIV, pregnancy,and drug use;
5. To identify causes and preventative
measures concerning the contraction of
the HIV virus and to detail briefly themechanisms of how the HIV virus works
to infect a person.

BACKGROUND

WHAT’SYOUR SIGN?

Antibodies areusually represented by a Y-shaped
symbol.

The immune system of the body plays acrucial role in fighting illness and in preventing disease. Regardless of whether a person
is attacked by something as common as anannoying cold virus or allergy, or as severe
as hepatitis or HIV, it is the immune systemthat the body calls to action, in some cases
more successfully than others. Althoughhumans generally prove quite resilient against
a host of bacterial and viral invasions, certain
diseases can overwhelm the immune system.
The progression of AIDS in an HIV-infectedindividual, for instance, cripples the immune
system so that it can no longer sustain aperson’s health.

THE IMMUNE SYSTEM
Immunology is the study of the immune
system, a system that protects the body froma host of foreign substances, toxins, andpathogens (agents that cause disease). A
healthy immune system can tell the difference between so-called “self” and “non-self.”
Just as young children grow and learn todistinguish themselves from other people, so,too, does the immune system create a distinction between one’s own body and outside
substances. Typically, examples of “non-self”
include foreign invaders such as viruses andbacteria. By fighting these “non-self” pathogens, the “self” ensures that it stays healthy.
A properly working immune system canalso tell the difference between “self” and“altered-self.” Cancer, or uncontrolled cell
growth, is an example of “altered-self.”
Cancer cells change themselves to the point
where they are destructive to the individual.
The immune system works hard to get rid of
these altered, cancerous cells. Other examplesof “altered-self” include normal cells that
become infected with a virus or bacteria.
The infection alters the cells and makes themtargets for the immune system.
Unfortunately, cases exist in which one’s own
body will turn against itself. Autoimmune
diseases occur when the body no longer
recognizes the “self”; in these cases, the bodywill attack itself. Like a dog chasing its tailbecause it cannot recognize the tail as its
own, the body cannot recognize its own cells
and systems. Examples of autoimmune diseases include common but serious conditions
such as multiple sclerosis and rheumatoid
arthritis.

KEY PLAYERS
An antigen is any substance that triggers
an immune response. When an antigen suchas a bacteria or virus attacks the body, thebody makes proteins called antibodies thatbind tightly to, neutralize, and help destroy
specific antigens. Also known as immunoglobulins, antibodies have Y-shaped structures. As shown in Figure 1, they have four
polypeptide chains – two so-called “heavy”
chains and two “light” chains.
The antigen-binding portion of the antibody
contains portions of both the heavy and lightchains. Often called the “hypervariable”
region, it allows for specificity of binding
between antibody and antigen. This variable
region of the antigen binding site can differ
greatly from one antibody to another.

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19

FIGURE 1: ANATOMY OF AN ANTIBODY
Antigen binding sites
Heavy chains

Light chain

Light chain
Constant
regionWEIGHTY
ISSUESAn antibody’s“heavy” and“light” chains areso called becauseof the length ofeach chain. The
heavy chain has
440 amino acids,
while the lightchain has 220.

An antibody’s protein structure
White blood cells (also known as leukocytes) play a key role in the body’s immune system. The body responds to foreign
invaders by calling white blood cells into
action. White blood cell (WBC) counts often
become elevated during infection. In cases of
immunodeficiency, however, WBC counts
tend to fall as a result of the body’s inability
to adequately fight infection. People infectedwith HIV, for instance, typically have low
WBC counts.
One white blood cell that plays a key rolein the immune response is the lymphocyte.
Humans have approximately twenty trillion(20,000,000,000,000 or 2 x1013) lymphocytes. These cells exist mostly in blood andthe lymphatic system, a part of the circulatory system that supplies fluids to maintainbalance in the body. The lymphatic system
assists with the body’s immune response.
Yet another important white blood cell of
the immune system is the macrophage.
Macrophages scout the body for foreign
invaders and devour them. A macrophage isan example of a phagocyte (or “eating cell”),
which is a cell that engulfs and takes inforeign material.

20

Computer model of an antibody molecule

IMMUNITY
Immunity is the body’s ability to respond to
antigens. Many different types of immunity
exist and they represent the variety of ways inwhich our bodies arm themselves to ward off
infection. The body responds to antigens in
the following ways:
1) INNATE IMMUNITY
The innate immune system serves as a firstline of defense against antigens (infectious
agents). It has four parts:• Anatomical barriers are parts of thebody, such as intact skin and mucous
membrane, that act as barriers to infectious agents.
• Physiological barriers include body
conditions, such as temperature and pH,that do not allow invaders to survive. For
example, our body temperature of 98°F isa harsh temperature that kills many invaders. A fever kills many of the invadersthat can survive under our normal bodytemperature. The acid in our stomach
also kills organisms that enter. The set ofphysiological barriers also contains two
important kinds of protein, interferon andcomplement.

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Interferon alerts the body to the presenceof an antigen (typically a virus or cancer);it then activates an adaptive and/or inflammatory response. Complement destroys
bacterial infections.
• Phagocytic barriers are created when
the white blood cells seek and destroy
infected cells through a process known asphagocytosis.
• Inflammatory response is the releaseof interferon that triggers chemicalsignals to fight infection. Some common
physical responses include fever, pain,
redness, and swelling. All these responses increase blood flow to damaged bodyareas in order to repair and eliminate
infectious agents.
		2) ADAPTIVE IMMUNITY
If antigens sneak through the first lines ofdefense, the body responds by eliminating the antigen and remembering it, so it
does not cause disease again. Two types ofadaptive responses exist. The humoral response makes antibodies. The cell-mediatedresponse makes specialized cells that kill
infected cells or recruit other cells to kill.

WHAT’SIN A NAME?
The B and T cells
are named after
the first lettersof the body parts
where theymature. The B cellmatures in thebone marrow.
The T cell starts
to develop in thebone marrow, but
it travels throughthe bloodstream
and matures inthe thymus.

There are two types of lymphocytes involvedin adaptive immunity. B cells produce antibodies in the humoral response. T cells, ofwhich there are two types, produce the cellmediated response:• Helper T cells (TH Cells) secrete
proteins that activate B and T cells in
response to an antigen.
• Cytotoxic T cells seek out and kill
infected cells.

THE IMMUNE SEQUENCEFirst, an antigen triggers the developmentof B and T cells, both of which come froma precursor cell made in the bone marrow.
When B and T cells are fully developed andarmed to fight against infection, they are
immunocompetent. They re-circulate fromblood to lymph to blood.

Photo by Janice Carr | Centers For Disease Control and Prevention

A scanning electron micrograph (SEM) of a white blood cell,magnified 7,766 times.
When a foreign invader such as a virus enters
the body, a macrophage engulfs it. Onceinside the macrophage, the virus is broken
into many pieces. These viral pieces attach
to a protein inside the macrophage called
major histocompatibility complex I (MHC)(Figure 2). Once the MHC protein binds
to the viral pieces, it moves to the plasma
membrane of the macrophage and presents
the viral proteins—the “antigens”—on theoutside surface of the macrophage cell.
Now that the viral proteins are on the outsideof the macrophage, an immunocompetent T
cell circulating in the blood stream can respond. Acting as a sort of “intelligence-gathering” cell, the T cell senses a virus present
in the body and triggers the adaptive immune
Response. The T cell then releases proteins
called lymphokines, an example of which isinterleukin. The lymphokine moves throughthe blood stream and activates immunocompetent B cells. The B cells multiply and dif-

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21

FIGURE 2: MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
A major histocompability complex protein binds to a foreign antigen after it has been engulfed by a macrophage and displays
it on the surface of the cell to alert Helper T cells.
The macrophage engulfs
the foreign antigen.

MHC proteins

Antigen

The antigen is broken
down into fragments.

The MHC proteins bind to
the antigen fragments.

The MHC proteins move to thesurface of the macrophage anddisplay the antigen fragments.

Helper T cells bind to the MHC
proteins and release Interleukin-2
to activate killer T cells and B cells.

ferentiate into two types of cells — plasma
cells and memory B cells. Plasma cells act as
the “weapons experts” to produce the antibodies that are specific to the antigen.
This elaborate sequence of events, from
infection to antibody production, typicallytakes several days, a delay referred to as lag
time. The secondary response occurs much
faster because of the formation of memory
B cells that act as “historians” to remember
the antigens. During a second infection of thesame antigen, memory B cells work quickly
to rid the body of the remembered invader(Figure 3).

of this rapid secondary response by intentionally exposing an organism to a harmless orless harmful form of a pathogen in order tostimulate the specific antibody response. If theorganism encounters another exposure to thesame pathogen, the quicker secondary response
is launched by the memory B cells.
The term passive immunity is used wheneverpreformed antibodies are transferred from an
immune organism to one that is not immune.
For instance, passive immunity occurs whena mother transfers her antibodies to the fetus.
Passive immunity is widely used in the treatment of immunodeficiency diseases.

Vaccinations are examples of passive immune transfer. Vaccinations take advantage

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FIGURE 3: PRIMARY AND SECONDARY RESPONSESPRIMARY RESPONSE
When a new antigen enters the body,it encounters a variety of B cells andbinds with the one with receptors that
fit it.

Antigen
Antigen binds toa specific B cell.

The selected B cell
multiplies anddifferentiates.

Plasma cell

Much of the clone is made up ofplasma cells that produce antibodies
to combat the antigen, but a few
become memory B cells that await
future exposure to the same antigen.

Antibodies
Memory B cell

SECONDARY RESPONSE
Later exposure to the same antigen
triggers the memory B cells.

The memory B cells trigger the productionof a larger clone of cells and more antibodies
than during the primary response.

Memory B cell

Immunological memory

Antibody concentration

The secondary immune response produces very high levels of antibodies that are often more
effective against the antigen than the antibodies produced during the primary response.

First exposure
to antigen X

Primary responseto antigen X

Second exposure
to antigen X;
first exposure toantigen Y

Secondary immune
response to antigen X

Primary responseto antigen Y
Antibodies
to antigen Y

Antibodies
to antigen X
0

7

14

21

28

35

42

49

56

63

70

77

time (days)
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23PRE-LAB

HIV: How it Functions

The pre-lab of this module introduces students
to a range of different diseases and how they
can be transmitted. Additionally, by assuming the characters of various cells and foreign
substances, students engage in a kinestheticrole play to understand how the different partsof the immune system work together in the
body’s defense. Through this activity, students
recognize that the different cells and parts of
the immune system all have unique parts toplay in fighting disease. The role play illustrates a sequence of events that rids the body ofunwanted material, and strengthens it throughthe use of “memory” cells that can operate in
future “attacks.”

HIV, or human immunodeficiency virus, isknown as a retrovirus. Instead of DNA, theHIV virus contains RNA. Using an enzyme
known as reverse transcriptase (recall
that the process of transcription normally
produces one strand of mRNA from DNA),the virus makes DNA from RNA, which isa process that is essentially the reverse ofthat in regular transcription. The virus thenincorporates its newly formed DNA into the
DNA of the host cell. Once integrated into thehost genome, the virus’s genetic information
replicates thousands of times to produce newviruses, which can then infect other cells.

Students learn the importance of specificity
within the immune system: antibodies willbind to an antigen with a particular shape or
specific sequence (epitope). In this case, theway in which the antibody’s shape in the roleplay will bind only to the specific antigen that“fits” mimics the way that true antibodies andantigens fit together biochemically.

WET LAB
In order to show how quietly, rapidly, andwidely a virus such as HIV can be transmitted from person to person, the wet lab begins
with an activity in which students “exchange
fluids” with classmates. A pH indicator called
phenolphthalein is used at the end of theexercise as a “test” to see who in the class has
contracted the virus.
In addition to illustrating how quietly avirus like HIV can spread, this activity also
provides a good review of acids and bases,
since the “virus” is actually NaOH, or sodiumhydroxide, which is a base.
In order to further promote awareness ofHIV, and to provide students with first-handscientific knowledge of how HIV testing is
performed in real life, students perform an
ELISA (enzyme-linked immunosorbent
assay). In addition to testing for antibodies
to HIV, the ELISA also forms the basis for
pregnancy and drug tests.

24

The presence of the HIV virus affects the level of CD4 cells, or helper T cells, in the body.
The number of CD4 cells in the body directly
relates to the viral load, which reflects bloodlevels of HIV. The higher the amount of HIV
in the blood, the higher the viral load and thelower the CD4 count. Research has shownthat low CD4 counts, particularly those below
200 cells/μl, indicate a much higher susceptibility to opportunistic infection. Because aperson with AIDS has a weakened immune
system, the system proves less able to fightinfections. Typically, people do not die
because of the HIV virus itself; rather, theydie because their weakened immune systems
cannot fight the host of opportunistic infections that take advantage of this weakness.
Criteria for a diagnosis of AIDS (as opposed
to HIV) include a CD4 count below 200, as
well as certain clinical criteria that relate toopportunistic infections.

THE ELISA
The enzyme-linked immunoabsorbent
assay (ELISA) offers a quick and accurate
test that can detect diseases in people, animals,
and plants, determine indoor air quality, andestablish if foods are labeled accurately.
Diseases spread by exchange of bodily fluids
such as HIV and SARS, diseases spread by
food-borne agents like E.coli 0157:H7, andalso diseases caused by vector transfers (e.g.,a tick transmitting Lyme disease) can bedetected using ELISA. The many varietiesof dipstick tests, including home pregnancy

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FIGURE 4: Enzyme-Linked Immunosorbent Assay (elisa)
The ELISA is a biochemical technique used primarily to detect the presence of an antibody oran antigen in a sample. It uses two antibodies. One is specific to the antigen, while the otheris bound to an enzyme (hence the “enzyme-linked” in the assay’s name).

Coloredproduct

EnzymeSerum antibody

SubstrateAnti-humanantibody

Antigen

A patient’s serumis exposed to theantigen. If thecorresponding
antibody exists,
it will bind to theantigen.

An anti-human antibody(secondary antibody)is added and binds tothe constant region of
the serum antibody. An
enzyme is bound to thissecondary antibody.

tests and tests for illegal drug use, can show
results in a matter of minutes. Dipstick tests
use immunochromatography, which relies on
many different antibodies to yield positive or
negative results.
A person exposed to a particular antigen
produces very specific antibodies in response.
These specific antibodies, contained in theantiserum, can be detected by an ELISA test.
ELISA is a lab tool that takes advantage ofthis specificity of antibodies.
To determine if these antibodies are present
in a patient’s serum, the serum is exposed tothe corresponding antigen bound to the plastic surface of a plate. The antigen, which is a
protein, attaches to the plastic as a result ofinteractions between the hydrophobic areasof the protein and the nonpolar surface of theplastic. If an antibody to the antigen is present in the serum, it will bind with the antigen
when added to the plate, as in Figure 4.
Even though the antibody and antigen bind toeach other, the reaction cannot be observed

A substrate is added tothe enzyme, resulting ina colored product. The
colored product indicatesthe presence of theantigen and the antibody
specific to that antigen.

without some kind of indicator. The next stepis to create an anti-human antibody that willbind to the constant region of the patient’s
serum antibody.
This anti-human antibody is commonly madeby injecting a goat or rabbit with the constantregion of human antibodies. The animal’s
immune system responds by making anti-human antibodies. A conjugate is formed whenthese anti-human antibodies are covalently
bonded. Next, these anti-human antibodies arecovalently bonded to chromogenic enzymes
that produce a color with addition of a substrate (Figure 4). Commonly used enzymes
include horseradish peroxidase, alkaline
phosphatase, and ß-galactosidase.

Treatments for Common Illnesses
So what happens when you feel sick and go
to the doctor? Often, the doctor will prescribe
antibiotics if you are not feeling well, in
response to a bacterial infection. An example
of a bacterium that causes disease is streptococcus, which causes strep throat.

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25Antibiotics, commonly prescribed for bacterial infections, killboth good and bad bacteria.
At other times, your doctor may tell you only
to rest and drink plenty of fluids. In this case,
you likely have a viral infection. Examplesof viral infections include chicken pox andthe flu. Such infections cannot be treated with
antibiotics, which may destroy componentsof the bacterial cell wall or affect a bacteria’s
metabolism.
Fortunately, some viruses such as these, as
well as some bacteria, can be prevented withthe help of a vaccine. A vaccine carries aweakened or dead form of a bacteria, virus, orpart of the virus. It provides material against
which your body can make antibodies as partof an immune response; however, the material is not strong enough to make you sick.
The next time your body gets the real bacteria
or virus, it remembers that you have alreadybeen infected with the weaker version, and it
can quickly respond.

Recently, there has been growing concern
about the overuse of antibiotics, because
these could lead to antibiotic resistance. The
idea is that, due to the process of natural
selection, bacteria with favorable characteristics will survive the antibiotics. After thesebacteria survive and multiply, they will passalong genes that are resistant to particularantibiotics. In this way, greater numbers ofbacteria are likely to be created that hold agenetic resistance to antibiotics. This is another reason to take all antibiotics prescribed
and to use antibiotics only when needed.

INTERDISCIPLINARY BRIDGESELISA forms the basis for a wide array oftests, including drug tests. Many high schools
across the country, including some in North
Carolina, have now adopted randomized drug
testing for students participating in extracurricular activities. A 2002 Supreme Court
ruling stated that this randomized testing isconstitutional, as long as the school restricts
the testing to those involved in extracurricular activities. One of the interdisciplinary
bridges asks students to discuss personal
feelings about this testing and conduct a
debate about the potential benefits and harmsof such tests. Finally, they will place the issue
within the context of the Bill of Rights andindividual privacy.

In some cases, physicians do prescribe
antibiotics to people with viral infections,particularly when their immune systems are
weak and susceptible to opportunistic bacterial infections. It is important for patients totake the full round of antibiotics prescribed,
even if they are feeling better after just thefirst or second dose. The antibiotics aredesigned to eliminate bacteria from the body;
but if only the first few doses are taken, thensome residual bacteria hang around and canmultiply. Because antibiotics kill both goodand bad bacteria, sometimes doctors recommend eating foods like yogurt in addition to
taking antibiotics. Yogurt contains bacterial
cultures that help to re-supply the body withgood bacteria.

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CONNECTION TO OTHER MODULES
The module Biological Bodyguards examines the vital role of the body’s immune
system in fighting illness and preventing
disease. Using an enzyme-linked immunosorbent assay (ELISA), students screen hypothetical patients for the presence of humanimmunodeficiency virus (HIV). The modules with accompanying wet-lab activities
presented here are all health science-related.
They also provide students the first-handexperience they need to understand common
practices used by biotechnologists in theirlabs daily.

MYSTERY OF THE CROOKED CELL

In this module developed by Boston University School of Medicine’s CityLab, students
learn about the genetic
basis for sickle cellanemia. Students
observe functional
differences in normal
hemoglobin and sickle
cell hemoglobin, which
result from a point
mutation. Electrophoresis is used as a tool todiagnose hypothetical patients for sickle celldisease. Both Mystery of the Crooked Celland Biological Bodyguards introduce students
to important diagnostic techniques used inmolecular biology labs.

WEIGH TO GO!

This module invites to students to explore
connections between obesity, diabetes, highblood pressure, andhigh cholesterol. Usinghydrophobic interactive
chromatography, a key
process in biotechnology research, students
purify a geneticallyengineered designerprotein (simulated
leptin) from transformed bacteria cells. Biological Bodyguards
and Weigh to Go! examine the body’s immune
system and the genetics and biochemistry of
specific diseases.

BIOBUSINESSIn BioBusiness, students discover how businesses use recombinant DNA technology
to tailor products tomeet customers’ needs.
Students perform aprocedure known as
genetic transformation,
which occurs whena cell takes up andexpresses a new pieceof genetic material ―DNA. The resulting organism is known as a
genetically modified organism or GMO. In
medicine, diseases caused by defective genes
are being treated by gene therapy, which is
genetically transforming a sick person’s cellswith healthy copies of the gene involved intheir disease. Like Biological Bodyguards,
BioBusiness is health related and introduces
students to concepts relating to the genetics
and biochemistry of specific diseases.

SEQUENCE OF MODULES

A sequence relating the four modules is summarized below:
1. MYSTERY OF THE CROOKED CELL
Students learn the genetic basis of sickle
cell anemia and diagnose patients for the
disease using gel electrophoresis.
2. WEIGH TO GO!
Students learn about the genetics andbiochemistry of weight. They examine
obesity as a disease that has reachedepidemic proportions.
3. BIOLOGICAL BODYGUARDS
Students examine the vital role of thebody’s immune system in fighting illness
and preventing disease.
4. BIOBUSINESS
Students perform a procedure known as
genetic transformation, which occurs whena cell takes up and expresses a new pieceof genetic material.

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27HIV FACT SHEET
What is HIV?

HIV (human immunodeficiency virus) is the virus thatcauses AIDS. This virus may be passed from one person to another when infected blood, semen, or vaginal
secretions come in contact with an uninfected person’s
broken skin or mucous membranes. In addition, infected pregnant women can pass HIV to their babies during
pregnancy or delivery, as well as through breast-feeding. People with HIV have what is called HIV infection.
Some of these people will develop AIDS as a result of
their HIV infection.

What is AIDS?

• AIDS – stands for acquired immunodeficiency
syndrome.
• Acquired – means that the disease is not hereditary but develops after birth from contact with adisease causing agent (in this case, HIV).
• Immunodeficiency – means that the disease
is characterized by a weakening of the immune
system.
• Syndrome – refers to a group of symptoms thatcollectively indicate or characterize a disease. In
the case of AIDS this can include the developmentof certain infections and/or cancers, as well as adecrease in the number of certain cells in a person’s
immune system.

A diagnosis of AIDS is made by a physician using specific clinical or laboratory standards.

How does HIV cause AIDS?

HIV destroys a certain kind of blood cell (CD4+ T
cells) that is crucial to the normal function of the humanimmune system. In fact, loss of these cells in people
with HIV is an extremely powerful predictor of thedevelopment of AIDS. Studies of thousands of people
have revealed that most people infected with HIV carrythe virus for years before enough damage is done to theimmune system for AIDS to develop. However, sensitive tests have shown a strong connection between theamount of HIV in the blood and the decline in CD4+
T cells and the development of AIDS. Reducing theamount of virus in the body with anti-retroviral therapies can dramatically slow the destruction of a person’s
immune system.

How is HIV passed fromone person to another?

HIV transmission can occur when blood, semen (cum),pre-seminal fluid (pre-cum), vaginal fluid, or breast
milk from an infected person enters the body of an
uninfected person.

28

A scanning electron micrograph of HIV viruses (the small round bumps)
budding from a lymphocyte.
HIV can enter the body through a vein (e.g., injection,
drug use), the lining of the anus or rectum, the lining of
the vagina and/or cervix, the opening to the penis, themouth, other mucous membranes (e.g., eyes or insideof the nose), or cuts and sores. Intact, healthy skin is
an excellent barrier against HIV and other viruses andbacteria.
These are the most common ways that HIV is transmitted from one person to another:• by having sex (anal, vaginal, or oral) with an
HIV-infected person;• by sharing needles or injection equipment with aninjection drug user who is infected with HIV; or• from HIV-infected women to their babies before
or during birth, or through breast-feeding after birth.
HIV also can be transmitted through receipt of infectedblood or blood-clotting factors. However, since 1985,
all donated blood in the United States has been tested
for HIV. Therefore, the risk of infection through transfusion of blood or blood products is extremely low. The
U.S. blood supply is considered to be among the safest
in the world.
Some health-care workers have become infected after
being stuck with needles containing HIV-infected bloodor, less frequently, when infected blood comes in contact
with a worker’s open cut or is splashed into a worker’seyes or nose. There has been only one documented
instance of a health-care worker infecting patients—anHIV-infected dentist in Florida who apparently infected
some patients while performing dental work.

What are the different HIV screening
tests available in the U.S.?

In most cases the EIA (enzyme immunoassay), performed on blood drawn from a vein, is the standard
screening test used to detect the presence of antibodies
to HIV. A reactive EIA must be used with a follow-up
confirmatory test such as the Western blot to make apositive diagnosis.

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BIOLOGICAL BODYGUARDS IMPLEMENTATION PLAN — PRE-LAB
Activity

Estimated TimeEngagement

10 minutes

Exploration

25 minutes

Explanation

15 minutes

Elaboration

30 minutes

Evaluation

10 minutes

Purpose/Objectives/
Essential Question

Materials/Equipment

Bag containing 6 stuffed microbes
responsible for the following diseases: HIV,kissing disease (mono), Ebola, syphilis,
tuberculosis, and influenza (or 6 index
cards, each listing one of the diseases)
Engagement Activity: Disease List With
Purpose:Symptoms sheet• To identify the anatomical and physiGlogerm powder
ological barriers related to the immune
Overhead transparency of humoral response system
One copy of the descriptions and diagrams • To explain the process involved in theof the components of the humoral
immune system’s operation
response for each group• To understand the concept of clonal
Props for role play exercise: instructions, la- selection
bels for participants, water bottle, models ofantibodies and antigens, (optional) Christy Objectives:
Lane’s Sports & Novelty Themes music• To develop and articulate ideas about
Television Show, “Dial in for a Dialogue
the body’s defense against pathogens
with a Doc”
• To identify the role of antibodies in the
Basic features of the immune system; 3rd
immune systemline of defense: special features (specificity, • To sequence the events of the humoral
diversity, self/nonself, recognition, memory) response of the immune system
Television Show, “Dial in for a Dialogue
Essential Questions:with a Doc”
• How does the body defend itself
Types of immunity; passive, active
Dual defense: humoral and cell-mediated against pathogens?
• What are the steps that make up the
responses
humoral response?
B and T cells
What happens when immune responsegoes awry; autoimmune diseases
Paper, pencil, worksheet to create concept
map of the humoral response

Alignment with NC Competency Goals
Biology
Goal 1
Objectives 1.01,1.02,1.03, 1.04, 1.05
Goal 2
Objectives 2.01, 2.02, 2.03, 2.04
Goal 3
3.01,3.04
Goal 4
Objectives 4.01, 4.03,4.04

Healthful Living
Goal 1
Objectives 1.02, 1.06
Goal 3
Objectives 3.01, 3.04, 3.07, 3.08, 3.09

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29BIOLOGICAL BODYGUARDS PRE-LAB ACTIVITIES:UTILIZING THE 5E INSTRUCTIONALENGAGEMODELENGAGEMENT

The teacher greets each student with a handshake as
they enter the room, and secretly transfers Glogerm
powder from his or her hand to the students’ hands.
Students then join one of six groups in the classroom.
As the bag of stuffed disease microbes ispassed among the six groups of students,
one student from each of the six groups
selects a stuffed disease microbe fromENGAGEthebag or selects an index card with the name of thedisease written on it from six index cards. The teacher
then uses a black light to detect the Glogerm on thestudents’ hands and explains that this Glogerm indicatesthe students have come into contact with a diseasecausing organism. The teacher circulates throughout
EXPLORE
thesix groups identifying symptoms of each group’s
particular disease. Finally, the teacher asks students toreflect. ... on
how their bodies respond to the invasion of. ...
......
... ...
....
....
....
..
............
these.... .......organisms.
..... ....
....
..

Exploration
EXPLAIN

Students are asked to describe in their own words thesteps in the overhead transparency of the immune sysENGAGE
tem
process known as the humoral response. After the
students share their descriptions with theclass, they take on the roles of the “major
ELABORATEplayers” in the immune response and engage
in a role play exercise. This role play activENGAGE
ity allows the class to visualize the antigen
EXPLOREENGAGE and the immune response when students take on
invasionthe “roles” of the immune system’s key players; antigen,macrophage,
B cell (Plasma cell), Helper T cell and
. ...
...
... ...
....
..... ....
..........
....
....
..
............
.... ....
....
Memory.. B cell.

EVALUATE
EXPLORE
Explanation/ELABORATIONEXPLAIN
EXPLORE• Causes of disease, including a review of Koch’s
Postulates• Nonspecific immunity versus specific immune
responses
EXPLORE• Lymphatic system involvement in the immune
response•. ......Thebody’s lines of defense in the fight against
...
...
....
..... ....
..........
....
....
..
............
....infection
....
....
..
• Two categories of the immune system response:
cell-mediated response and the humoral response
EXPLAIN• Autoimmune diseases• Immunodeficiency diseases: SCID, HIV, andthose induced by immunosuppressive drugs

Evaluation

ELABORATE

The evaluation activity serves to assess whether students
have grasped the answer to the essential question:
how does your body defends itself against
foreign invaders? Students are asked tocomplete a concept map to assess their understanding of the body’s humoral response,
EVALUATEthe major components and the order in which
includingthey appear.

THE 5E’s

A television
show called “Dial in for a Dialogue with a
. ...
...
... ...
....
..... ....
..........
....
....
....
..
...
.....
Doc”
providesa format for a more complete investiga.... ....
....
..
.
...
...
tion
of the immune system. One group of
.
...
...
... ....
.... ....
...........
....
..
............
.... ....
....
students call in with their questions and are..
EXPLAIN provided answers by a group of students
ELABORATEplaying a panel of doctors.

EXPLAIN

During this elaboration phase, students

THE 5E’s have an opportunity to correctly use techniELABORATE cal vocabulary and apply scientific reason-ing. The instructor acts as a mediator and facilitates
thediscussion between the two groups. Some of the
ELABORATEEVALUATE
concepts covered during this “television show” are as
follows:

30EVALUATEEVALUATE

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BIOLOGICAL BODYGUARDS PRE-LAB ACTIVITIES
Purposes• To identify the anatomical and physiological barriers related to the immune system• To explain the process involved in the immune system’s operation• To understand the concept of clonal selection

Objectives• To develop and articulate ideas about the
body’s defense against pathogens• To identify the role of antibodies in the immune system• To sequence the events of the humoral
response of the immune system

Engagement Activity
Materials NEEDED• Glogerm powder• Bag of 6 stuffed microbes (one per group)or 6 index cards, with one of these diseases
written on each card: HIV, mononucleosis(“kissing disease”), Ebola, syphilis, tuberculosis (TB), and influenza.
• Engagement Activity: Disease List With
Symptoms sheet.

INSTRUCTIONS FOR TEACHERS• Secretly put Glogerm powder on your hands
before class and shake hands with each student, or as many students as possible, as they
enter the classroom.
• Arrange the students into six groups. Have
one student from each of the six groups
choose one stuffed disease microbe from themicrobe bag (or one of the index cards) andencourage them to pass it around to membersof their group.

• Start to cough, then explain that some ofthe students have been exposed to organismsthat may cause a cold or influenza when they
shook your hand as they entered the room.
• Use a black light to detect Glogerm powder
on students’ hands, indicating that students
have come in contact with a disease-causingorganism.
• Ask the students, “How do you feel?”
Explain that they do not look very good. Thenmove around the room identifying symptoms
expressed by each group based upon which
stuffed microbe or index card they selected.
(Symptoms for each disease can be found on
the following page entitled Disease List With
Symptoms.)• Explain that the students’ bodies havebeen invaded by these villains and ask thestudents, “How does your body respond toinfection/infections?” Allow five minutes forstudents to reflect before asking them to share

Stuffed microbes, each representing a disease.
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31Disease List with Symptoms

Sources: adapted from information available at www.webmd.com and www.disability.vic.gov.au
Ebola Hemorrhagic Fever (HF)

Human Immunodeficiency Virus (HIV) Infection

The signs and symptoms of Ebola
HF are not the same for all patients.
The table below outlines symptomsof the disease, according to the frequency with which they have beenreported in known cases.

HIV infection progresses in stages. These stages are
based on an individual’s symptoms and the amount of
the virus in the blood.

Time frame

Symptoms that
occur in most
Ebola patients

Symptoms that
occur in some
Ebola patients

Within a few
days of becoming infectedwith the virus

High fever,headache,muscle aches,
stomach pain,
fatigue, diarrhea

Sore throat,
hiccups, rash,
red and itchy
eyes, vomitingblood, bloody
diarrhea

Within one
week of becoming infectedwith the virus

Chest pain,
shock, and death

Blindness,bleeding

Initial stage: Flu-like symptoms often appear within
3 to 6 weeks of initial exposure to the virus, althoughsymptoms can develop within just a few days. This firststage is called acute retroviral syndrome. Symptomsof acute retroviral syndrome are often mistaken for
symptoms of another viral infection, such as influenza
or mononucleosis, and may include:• Abdominal cramps, nausea, or vomiting• Diarrhea• Enlarged lymph nodes in theneck, armpits, and groin• Fever• Headache• Muscle aches and joint pain
• Skin rash
• Sore throat• Weight loss.

Researchers do not understand why some people areable to recover from Ebola HF and others are not.
However, it is known that patients who die usually
have not developed a significant immune response to
the virus at the time of death.

Influenza

The symptoms of influenza (flu) appear suddenly and often include:• Fever of 100°F (37.8°C) to 104°F (40°C), which can reach 106°F (41.1°C) when symptoms first develop.
Fever is usually continuous, but it may come and go. And it may be lower in older adults than inchildren and younger adults.
• Shaking chills.
• Body aches and muscle pain
(often severe), commonly in the back, arms, or legs
• Headache• Pain when moving the eyes.
• Fatigue, a general feeling of sickness (malaise), and loss of appetite• A dry cough, runny nose, and a dry or sore throat. The infected individual may not notice these during the firstfew days of the illness, when other symptoms are more severe. As the fever goes away, these symptoms may
become more evident.

32

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Mononucleosis

The early symptoms of mononucleosis, which resemble
those of the flu, include:• Deep fatigue• Sore throat• Headache• Chills, followed by a fever• Muscle aches.
After a day or two, the following additional symptoms
may occur:• Swollen lymph nodes• Jaundice (a yellow tinge to the skin and eyes).
• A measles-like skin rash anywhere on the faceor body. (Sometimes the rash develops suddenly
after the infected individual takes amoxicillin fora severe sore throat.)• Tiny red spots or bruise-like areas inside themouth, especially on the roof of the mouth(palate)• Soreness in the upper-left abdomen (from anenlarged spleen).

Tuberculosis (TB)

Individuals who have latent TB do not have symptoms
and cannot spread the disease to others. Individuals
who have active TB do have symptoms and can spreadthe disease to others. The specific symptoms depend onwhether the infection is in the lungs (the most commonsite) or in another part of the
body (extrapulmonary TB).

Syphilis

Syphilitic infection unfolds in 3 distinct stages.
First Stage (4 to 6 weeks): At this stage, syphilis canbe recognized by one or more sores on the penis, vulva(lip of the vagina), anus, or mouth. These sores, which
are usually painless, may also be hidden from view inthe rectum or on the cervix. This symptom usually appears 3-4 weeks after infection, but can occur between
10 and 90 days after infection. The sores usually heal
completely in 4-6 weeks.
Second Stage (0-12 months): This stage of syphilis ischaracterized by a highly contagious rash on the solesof the feet or palms of the hands.
This flat, red rash may also cover theentire body. Other symptoms include
enlarged lymph nodes, hair loss,
lumps on the genitals, and general
tiredness. Individuals who do notreceive treatment can remain infectious for up to two years.
Third Stage (may occur years later): If left untreated,
the syphilitic infection may progress to this stage,
which is characterized by severe problems with theheart, brain, and nerves. Results can include blindness,dementia, impotency, and even death.

Symptoms of active TB in
the lungs: Symptoms of active TB begin gradually and develop over a period ofweeks or months. Someone infected with TB may haveone or two mild symptoms and not even be aware of
having the disease. Common symptoms may include:• Coughing up thick, cloudy, and sometimes bloody
mucus (sputum) from the lungs for more than two
weeks• A rapid heartbeat• Swelling in the neck (because lymph nodes in theneck become infected).

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33

EXPLORATION ACTIVITY, PART 1
MATERIALS NEEDED• Copies of the sheets listing the steps of the humoral response• Transparency of the humoral response

INSTRUCTIONS FOR TEACHERS

Using the same small student groups, give each group a sheet listing the main components of the humoral response andplace the overhead transparency of humoral response (Figure 5) for the class to see. Ask students to list and describe thesteps in the humoral response in their own words.

34

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NAME _______________________________________

Exploration Activity: Part 1
In your own words, describe the steps in the diagram of the immune system process (humoral response).
Invader identification phase

Cloning phase

Attack phase

Slowdown/memory cell phase

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35

FIGURE 5: HUMORAL RESPONSE

36

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Exploration Activity, Part 2
Students will act out the invasion of the body by anantigen. Using the analogy of the armed forces, students
take on the defensive roles of the humoral response.

MATERIALS NEEDED• (optional) Christy Lane’s Sports & Novelty Themes
music CD (available at www.christylane.com)• CD player• Water bottle for the Helper T cell to spray or activate
the B cell to make antibodies• Role-play cards with instructions• Labels for participants• Shapes of antibodies and antigens (print color copies
on color card stock and cut out ahead of time)○ 2 copies of shape A (fold one of the shapes along
the center line to form shape B)○ 10-15 copies of shape D (fold 2 copies along thecenter line to form shape C)• Helper T cell (Central Intelligence Agency, or CIA, ofthe body) — Enter when you hear track #10, Mission
Impossible. You can discern what isneeded to battle the antigen. Once a
macrophage, the “Inspector General,”shows you shape B, you spring into action. To accomplish your job, you must
pass shape C onto the B cells as you squirt the B cellwith water (cytokine) to activate them into action.
• B Cell (The Arms Expert) — Enter when you heartrack #25, Stars & Stripes Forever. You can launch a
precise campaign by producing the
precise ammunition to attack the antigens. Once the Helper T cell presents
shape C to you and has activated you
by squirting you with water (cytokine), you will mature into plasma cells to produce the“exact fit” antibodies to destroy the antigen.

INSTRUCTIONS FOR TEACHERS• Select several participants to be the actors in this roleplay exercise.
• Give all participants time to read their role play cards
and then allow them to act out the scene of an antigen
invasion.
• Provide the shapes of the antigens and antibodies tothe participants as follows.

• Plasma Cell — As a plasma cell, take shape C andunfold it to form the “exact fit” (shape D) to latch onto
the antigen. Throw these “exact fit”
antibodies out among the antigen.
These weapons (antibodies) will
destroy only the antigens with shapes
complementary to them.

Shapes:

A

B

C

D

Roles for the participants:• Antigen (The Body’s Alien Invader) — Enter when
you hear track #34, Jaws. Acting as
an antigen, you will carry shape A
with you. This shape is detected by
the macrophage as a “wrong uniform” and stimulates macrophages into action.

• Memory B Cell (The Chronicler/Archivist) — Enter when you hear track #7, Na Na Hey Hey. As you
chronicle the events that occur when the immune
system launches this specific response, you must record
the wrong “uniform” of marker molecules(shape A) worn by this particular antigen
and also the antibody shape used to stop theattack (shape D). The next time the enemy
invades, you are authorized to immediately direct B
Cell to start production of those particular weapons(antibodies).

• Macrophage (The Inspector General) —Enter when you hear track #43, Pink Panther Theme.
Acting as the “Inspector General” inthe body, you are on the lookout for any
foreign invaders. You can identify these
foreign invaders by the “uniform” orshape they carry. Once you ID a foreign invader (antigen), carry shape B to activate Helper T cells.
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37

Exploration Activity, Part 2 ROLE PLAY CARDS

Role

Shape

ANTIGEN(THE BODY’S
ALIEN INVADER)A

Macrophage(The Inspector
General)B

38

Instructions

Enter when you hear track #34,
“Jaws.” Acting as an antigen, youwill carry shape A with you. This
shape is detected by the macrophage as a “wrong uniform,” identifying you as an invader and stimulating macrophages into action.

Enter when you hear track #43,
“Pink Panther Theme.” Acting as
the “Inspector General” in thebody, you are on the lookout for
any foreign invaders. You can identify these foreign invaders by the
uniform or shape they carry. Once
you ID a foreign invader (antigen),carry shape B to activate Helper T
cells.

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Role

Shape

Helper T Cell
(CentralIntelligence
Agency, or CIA,of the body)C

Instructions
Enter when you hear track # 10,“Mission Impossible.” You can discern what is needed to battle theantigen. Once a macrophage, the“Inspector General,” shows you
shape B, you spring into action.
To accomplish your job, you must
pass shape C onto the B cells as you
squirt the B cell with water (cytokine) to activate them into action.
Enter when you hear track # 25,“Stars & Stripes Forever.” You canlaunch an exact campaign by producing the precise ammunition to
attack the antigens.

B Cell(the Arms
Expert)C

Once the Helper T cell presents
shape C to you and has activated
you by squirting you with water(cytokine), you will mature into
plasma cells to produce the“exact fit” antibodies to destroy the
antigen.

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39

Role

Shape

plasma cell

D

Memory B Cell(theChronicler/
Archivist)

40

Instructions

As a plasma cell, take shape C
and unfold it to form the “exactfit” (shape D) to latch onto theantigen. Throw these “exact fit”
antibodies out among the antigen.
These weapons (antibodies) will
destroy only the antigens withshapes complementary to them.
Enter when you hear track #7, “NaNa Hey Hey.” When you chronicle
the events that occur as the immune system launches this specific response, you must record
the wrong “uniform” of marker
molecules (shape A) worn by thisparticular antigen and also theantibody shape used to stop theattack (shape D). The next time theenemy invades, you are authorized
to immediately direct B Cell tostart production of those particular
weapons (antibodies).

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INSTRUCTIONS FOR TEACHERS• Make copies of this page on color card-stock paper and cut out the antibody shapes.
• Make copies of the next page (antigen shapes) on card-stock paper of a different color and cut
out the antigen shapes.
• Distribute the shapes to students in the role-playing activity. Each student playing the role ofan antigen gets an antigen shape. Each student playing the role of a macrophage gets an antigen
shape folded in half vertically. Each student playing the role of a Helper T cell or a B cell getsan antibody shape folded in half vertically.

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41

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Explanation/Elaboration BACKGROUND INFORMATION
The following topics are addressed in the “Dial in for a Dialogue with a Doc” activity that follows.

THE causes OF diseases

FIGURE 6: ANTIGENIC DETERMINANTS

Antigens are not whole pathogens. They are moleculesthat may be chemical components of a pathogen’s
surface. Pathogens are types of antigens that cause
disease and include viruses, bacteria, fungi, protozoan,
and prions.

Antibodies bind to specific regions on the antigen molecule called antigenic determinants. Antibodies’ antigen-binding sites and the antigenic
determinants they bind to have complementary shapes. An antigen
molecule usually has several different determinants, so different antibodies can bind to the same antigen.

Koch’s Postulates (Figure 8) established the germ
theory of disease in 1876.

Antigenic
determinants

Antigen molecule

The body’S defense system

Lymphatic system (thymus and lymph nodes; Figure 9)
Types of immunity• Innate• Acquired or adaptive vs. passive(transferring antibodies)• Supplemental body defenses○ Vaccines○ Antibiotics
Nonspecific immunity (Figure 10A)
1. First line of defense• Skin and mucous membranes• Cilia, sweat, and tears (many body secretions
contain lysosomes)• Acid secretions of the stomach• Fever• Symbiotic bacteria
2. Second line of defense: nonspecific mechanisms• Interferon (IFNs) — secreted by cells invaded byviruses that stimulate neighboring cells to produce
proteins that help them defend against viruses.
○ Genetic engineering and mass production ofinterferons began in the early 1980s.
○ Interferons show promise against many viraldiseases and some cancers.
• Natural killer (NK) cells, phagocytic cells (neutrophils and monocytes)• Complement system — a group of about 20 proteins that “complement” defense reactions. They
help attract phagocytes to foreign cells anddestroy foreign cells by promoting cell lysis.
• Inflammatory response — mast cells — initiate
the immune response○ Mast cells produce histamines, which increases
blood flow to the surrounding tissues.
○ Antihistamines

Antibody

Antigen-binding sites
3. Third line of defense (Figure 10B): immune response(targeted at specific antigens)• Specificity: self /nonself recognition, MHC(tissue rejections)○ MHC (major histocompatibility complex) or
HLA (human leukocyte antigens)○ Antigen antibody specificity
Five classes of antibodies, each associatedwith a particular activity: IgG; IgA; IgM;
IgD; IgE○ Antibody Structure/epitopes (antigenic determinants, Figure 6)
Diversity — explanation of how the immune system produces millions of different antibodies• Lymphocytes: formation of T cells and B cells○ Types of T Cells — pass through the thymus(Helper T CD4+, CD8+ Killer or cytotoxic,
Memory T)○ B Cells originate and mature in bone marrow, become plasma cells, memory B cells○ Immunocompetence• Immunological memory (Memory B & T cells)○ Primary and secondary immune response

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43

The responses of the immune system are categorized into two kinds of reactions:
1. Cell-mediated (mostly uses T cells andresponds to any nonself cell, including cells
invaded by pathogens)
2. Humoral response (or antibody-mediatedresponse)
What happens when the immune system goes awry?
• Hypersensitivity (Figure 11) — occurs when the
immune system overreacts to an antigen. Examples include: allergy, anaphylactic reactions, andcontact sensitivity (such as to poison ivy).
• Immunodeficiency — occurs when individuals cannot mount an effective immune response(SCID or “bubble boy” disease, HIV, or immunosuppressive drugs).
• Autoimmune diseases result from the immune
system inappropriately mounting an immune
response against itself.

○ Examples include: lupus (systemic lupus
erythematosus, SLE), rheumatoid arthritis,
scleroderma, and Sjogren’s syndrome, which
affect a wide range of tissues; diabetes (insulin dependent), which affects the pancreas;
Crohn’s disease, which affects the bowel;
Graves disease, which affects the thyroid;
chronic fatigue syndrome.
Clonal selection occurs when an antigen introduced into
the body activates only a tiny number of lymphocytes.
These “selected” cells then proliferate, forming a cloneof cells (a population of genetically identical B cells or
T cells).
Monoclonal antibodies (Figure 7) occur when all cells
producing the antibodies are descendants of a single cell.
Monoclonal antibodies are harvested from cell cultures
rather than from animals. They show great promise intreating diseases such as cancer.

FIGURE 7: MONOCLONAL ANTIBODIES

Antibodies
Antigen injected into
mouse to stimulate B cells
to make antibodies.

B cells (from spleen)

Single hybrid cellgrown in culture.

Hybridcells
Tumor cells grown in culture.

44

Tumor cells

Cells fused
to createhybrid cells.

Hybrid cell
culture,producingmonoclonal
antibodies.

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FIGURE 8: KOCH’S POSTULATESFINDING THE CAUSE
Robert Koch, a German physician who discovered rod-shaped bacteria in the
blood of cattle suffering from anthrax, used these four diagnostic criteria for
identifying disease-causing bacteria:

1
2
3
4

The same, specific pathogen must be identified in each animal(host) that has the disease.
The pathogen must be isolated from a host and grown in apure culture, one in which no other kinds of cells are present.
The original disease must be produced in experimental hoststhat are inoculated with the pathogen from the pure culture.
The same pathogen must be isolated from the experimental
hosts after the disease develops in them.

USUAL PROCEDURE FOR DEMONSTRATING KOCH’S POSTULATESThe bacterium
is identified.
Diseased animal

The suspected pathogen is
extracted from the animaland grown in a pure culture.

Bacteria from the second
animal are grown in apure culture.
Disease occurs inthe second animal.

The identical bacterium
is identified in the second
culture, thus proving that
it is the pathogen.

The bacteria from thepure culture is injected
into a healthy animal.

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45

FIGURE 9: THE LYMPHATIC SYSTEM
The lymphatic system is a network of vessels, tissues, and organs that helps the body regulate fluid balance and fight infection.

Lymph nodeCapsuleTrabecula

ArteryAdenoid

Efferent
lymphatic
vessels
Tonsils
Thoracic duct

The spleen is thelargest lymphoidorgan and acts as a blood
reservoir where worn-out
red blood cells are removed
from the blood.

Vein

Lymph
noduleAfferent lymphatic vessels
Lymph nodes are clustered along lympathic vessels. Eachnode is surrounded by a capsule and divided into compartments that contain a network of fibers, which supports
lymphocytes and macrophages.

T cellsdevelopin thethymus.

Appendix

Lymphatic vessels
Valve

Interstitial fluid

B cells develop in the bone marrow.
Tissue cells
Blood capillary

Lymphatic vessel
Flow of lymph

46

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FIGURE 10A: THE THREE LINES OF DEFENSE
The human body has three layers of defense mechanisms against infection.
Microbes enter the
body through a cut inthe skin.

The skin acts as a wall to prevent
pathogens from entering the body,while internal surfaces of the bodyare covered by mucous membranes
that trap pathogens.

Microbes
Chemical signals

Macrophages

If pathogens get past the skin and mucous
membranes, the next line of defense involves microbekilling cells (macrophages, neutrophils, and natural killer cells), complement
proteins (which kill invading microbes), the inflammatory response (which
suppresses infection and speeds healing after an injury or local infection), andthe temperature response (macrophages send signals to cause a fever, whichraises the body’s temperature to suppress bacteria growth).

PICTURED: INFLAMMATORY RESPONSE
When microbes invade the body through an injury or infection,
chemical signals increase the flow of blood to the site of theinfection and alert macrophages and neutrophils, which attack
invading microbes at the infection site.

The macrophage engulfs andconsumes the microbes.

B cellsIf pathogens get past the second line of defense
and cause illness, the body’s immune system
responds (see Figure 10B for details).

T cells

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FIGURE 10B: THE THIRD LINE OF DEFENSE — THE IMMUNE SYSTEM
Antigens slip past
the first two linesof defense.

Macrophage

Macrophages send an alarm signal
by releasing interleukin-1.

Helper T cells receive
the alarm signal.

Interleukin

Virus fragment

Helper T cells releaseinterleukin-2 toactivate B cells.

Helper T cells
activate killer
T cells.

B cells multiply
and differentiate
into two types.

Killer T cells
bind to bodycells that havebeen infected.

Most B cells
become plasma
cells that produce
antibodies.

A few B cells become memory cells
that continue to patrol the body. If theyencounter the same antigen again, thememory cells will start the productionof antibody-producing cells geared
specifically toward that antigen.

Antibodies attach
to the antigen.

Antibodies attract
macrophages andnatural killer cells
to the antigen.

48

The macrophage engulfs theantigen and consumes it.

Killer T cells destroy
infected cells bypuncturing theircell membrane.

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FIGURE 11: STAGES OF AN ALLERGIC REACTION
Sensitization: Initial
exposure to allergen

B cells makeantibodies

Pollen grains
Antigenic
determinants

Histamine

Protein moleculeson pollen grains
are a common typeof allergen.

Antibodies attach to mast
cells, normal body cells
that produce histamineand other chemicals thattrigger the inflammatory
response.

Later exposure tosame allergen

Histamine is released,causing allergy symptoms.

Allergen binds
to antibodies
on mast cells.

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49Explanation/Elaboration ACTIVITY:
TV SHOW, Dial in for A Dialogue with a Doc
INSTRUCTIONS FOR TEACHERS

Make a copy of the questions and questions with answers. Cut the strips apart and distribute the questions to one
group of students and the questions with answers to the other group of students.

Extension

Have students come up with some questions of their own. They can research the answers and report back to the group.

QUESTIONS

1. I don’t feel well. What could make me so sick?
2. How does the body defend itself against disease? What are the body’s first line of defense, second line of defense
and third line of defense? Why are burn patients more likely to have infection?
3. How is a vaccination like an artificial infection? Is the protection resulting from a vaccination considered activeor passive immunity?
4. What are interferons and what do they interfere with? What is our complement system and what does itcomplement?
5. I got a splinter in my finger and the doctor said my inflammatory response would protect me. What is the
inflammatory response?
6. How does an antibody differ from an antibiotic?
7. What would happen if a person was born without a thymus? What is the function of the lymph system? Why dolymph nodes swell when you have an infection?
8. How are MHC surface markers analogous to your fingerprints? What is the significance of the MHC in the
immune response?
9. I have heard that the B and T cells are soldiers of the immune response. How and where are T cells and B cells
formed? What is meant by the term immunocompetence?

10. How is my body capable of making so many different types of antibodies? How does the structure of an
antibody promote its function?
11. Why do we refer to certain diseases, such as mumps, as “childhood diseases”? What is the difference between
the primary and secondary immune responses?
12. I have heard that the immune response does not always involve the production of antibodies. Is this true?
13. I have allergies and I am especially sensitive to poison ivy. What causes this?
14. My aunt is to receive a liver transplant. What can be done to increase the chances that it will be successful?
15. My friend’s mother has cancer and she is being treated with monoclonal antibodies. What are monoclonal
antibodies?
16. Why is it so difficult to develop an effective vaccine against AIDS?
17. Why are you more likely to get sick during final exams than during summer vacation?

50

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Explanation/Elaboration ACTIVITY: Dial in for A Dialogue with a Doc

KEY

1. I don’t feel well. What could make me so sick?
Antigens. They are not whole pathogens; they are molecules that may be chemical components of a pathogen’s
surface. Pathogens are types of antigens that cause disease, including viruses, bacteria, fungi, protozoan, andprions.
Koch’s Postulates — presently known as the germ theory of infectious disease. German bacteriologist RobertKoch came up with these rules for proving that a specific type of organism causes a specific type of disease:i. The microorganism should always be found in the body of the host organism and not in a healthyorganism.
ii. The microorganism must be isolated and grown in a pure culture away from the host.
iii. When the microorganisms grown in pure culture are injected into a new host organism, they produce disease.
iv. The same microorganisms should be reisolated from the second host and grown in pure culture,
after which the microorganisms should still be the same as the original microorganisms.
Koch’s Postulates still guide microbiology and epidemiology, but there are many exceptions. Many pathogens(including the ones that cause AIDS and syphilis) cannot be grown in culture, making the second statement,
postulate ii, impossible to achieve.
2. How does the body defend itself against disease? What are the body’s first line of defense, second line of defense
and third line of defense? Why are burn patients more likely to have infection?
First line of defense• Skin and mucous membranes• Cilia, sweat and tears (many body secretions contain lysosomes)• Acid secretions of the stomach• Fever• Symbiotic bacteria
Second line of defense: nonspecific mechanisms• Interferon (IFNs) — Secreted by cells invaded by viruses that stimulate neighboring cells to produce
proteins that help them defend against viruses.
○ 1980 genetically engineered and mass produced; shows promise against many viral diseases andsome cancers• Natural killer (NK) cells, phagocytic cells (neutrophils and monocytes).
• Complement system — a group of about 20 proteins that “complements” defense reactions. They
help attract phagocytes to foreign cells and destroy foreign cells by promoting cell lysis.
• Inflammatory response – mast cells – initiate the immune response○ Mast cells produce histamines (increase blood flow to the surrounding tissues)○ Antihistamines
Third line of defense: immune response (targeted at specific antigens)
Burn victims are more likely to have an infection because their skin, the first line of defense, is damaged.
3. How is a vaccination like an artificial infection? Is the protection resulting from a vaccination considered activeor passive immunity?
A vaccination contains dead or attenuated pathogens. Vaccinations cause the body to make its own antibodies so
it is considered to be acquired or adaptive and active immunity.

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51

4. What are interferons and what do they interfere with? What is our complement system and what does itcomplement?
Inteferons are substances secreted by cells invaded by viruses that stimulate neighboring cells to produce proteins that help them defend against the virus.
Complement is a group of about 20 proteins that “complement” defense reactions. These proteins help attract
phagocytes to foreign cells and help destroy foreign cells by promoting cell lysis.
5. I got a splinter in my finger and the doctor said my inflammatory response would protect me. What is the
inflammatory response?
The inflammatory response consists of a series of nonspecific events that occur in response to pathogens.
Histamines are produced by mast cells, causing dilation of the blood vessels. Chemical gradients of complements attract phagocytes to the injury, where they engulf pathogens and damaged cells.
6. How does an antibody differ from an antibiotic?
Antibiotics are produced by living organisms and combat disease by weakening certain microorganisms, such asbacteria and fungi. Antibodies are produced by B cells and combat specific antigens.
7. What would happen if a person was born without a thymus? What is the function of the lymph system? Why dolymph nodes swell when you have an infection?
Your T cells would not be immunocompetent. T cells must pass through the thymus to become immunocompetent. The lymph system consists of the thymus and bone marrow and is the site where white blood cells develop.
It also consists of the lymph nodes which filter bacteria. (These swell when you are fighting infection, as a resultof the multiplication of defensive lymphocytes.)
8. How are MHC surface markers analogous to your fingerprints? What is the significance of the MHC in the
immune response?
MHC markers are unique to each individual. The MHC (major histocompatability complex), also known as the
HLA (human leukocyte antigens), consists of about 20 different proteins located on the surfaces of body cells
that identify “self” to the immune system. Identical twins would have identical MHC proteins.
9. I have heard that the B and T cells are soldiers of the immune response. How and where are T cells and B cells
formed? What is meant by the term immunocompetence?
B cells are lymphocytes that originate and mature in the bone marrow (B for bone). B cells respond to antigens.
The plasma membrane surface of B cells has specialized antigen receptors called antibodies, which serve as
biological ammunition.
T cells are lymphocytes that originate in the bone marrow, but mature in the thymus gland (T for thymus). The
plasma membranes of T cells have antigen receptors that are recognition sites for molecules displayed by nonself cells. When T cells encounter nonself cells, they divide and produce cytotoxic T cells (or killer T cells) andhelper T cells, which stimulate the proliferation of B cells and cytotoxic T cells.

52

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10. How is my body capable of making so many different types of antibodies? How does the structure of an
antibody promote its function?
Because of the randomness of possible combinations of specific parts of antibody genes that are cut, reshuffled,
and assembled, billions of different combinations of antibodies are possible. Only cells producing antibodies toinvading antigens are selected to multiply.
Genes are expressed in two stages. First, the V, D, and J gene segments move closer together when enzymes
remove the introns (segments that separate the coding regions). Second, the resulting DNA chain is transcribed
into RNA, along with RNA representing the C portion of the gene. This RNA is translated into an antibody
protein (Figure 12).

FIGURE 12: ANTIBODY DIVERSITYHEAVY-CHAIN DNA REARRANGEMENTV1 V2 V3

D1 D2 D3

J1 J2 J3

LIGHT-CHAIN DNA REARRANGEMENTC

1

V1 V2 V3

D1 D2 D3

J1 J2 J3

C1
introns2

introns

deleted segments

2

A stretch of DNA is deleted,resulting in the joining of a
D segment and a J segment.

A stretch of DNA is deleted, resulting in thejoining of a V segment and a J segment.

3
Another stretch of DNA isdeleted, resulting in thejoining of a V segment to
the joined D and J segments.

deleted segments

resulting DNA chain,
4 Thewith the VDJ joining a C

3

The resulting DNA chain, with
the VJ joining and a C segment,
is transcribed into RNA.

4The VJ segments are joined
to the C segment during RNA
splicing.
deleted segments

segment, is transcribed into RNA.
VDJ segments are joined
5 The
to the C segment during RNA
splicing.

deleted segments

deleted segments

5

The resulting RNA is translated
into light-chain protein.

resulting RNA is translated
6 The
into heavy-chain protein.

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5311. Why do we refer to certain diseases, such as mumps, as “childhood diseases”? What is the difference between
the primary and secondary immune responses?
Because once you have the disease, which usually occurs during childhood, you are generally protected for the
rest of your life. The primary response refers to the initial phase of your body’s response when you first comeinto contact with the pathogen. It occurs more slowly than the secondary response, which results from a second
exposure to the same antigen.
12. I have heard that the immune response does not always involve the production of antibodies. Is this true?
Yes. The responses of the immune system are categorized into two kinds of reactions:• Cell-mediated (mostly uses T cells and responds to any nonself cell, including cells invaded by pathogens)• Humoral response (or antibody-mediated response)
13. I have allergies and I am especially sensitive to poison ivy. What causes this?
Hypersensitivity occurs when the immune system overreacts to an antigen (allergy, anaphylactic reactions, andcontact sensitivity to substances such as poison ivy).
14. My aunt is to receive a liver transplant. What can be done to increase the chances that it will be successful?
Using immunosuppressive drugs to suppress the immune response.
15. My friend’s mother has cancer and she is being treated with monoclonal antibodies. What are monoclonal
antibodies?
Monoclonal antibodies are harvested from cell cultures rather than from animals. All cells producing the antibodies are descendents of a single cell. Monoclonal antibodies, which recognize one specific region on one
protein or immunogen, show great promise in treating diseases such as cancer.
16. Why is it so difficult to develop an effective vaccine against AIDS?
The HIV virus evolves so rapidly that it is difficult to develop an effective vaccine. New therapies such as drug
combinations called the drug cocktails (composed of protease and RT inhibitors) have provided hope and at
least temporary relief from disease progression.
17. Why are you more likely to get sick during final exams than during summer vacation?
Stress suppresses the immune response.

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Evaluation Activity: The Humoral Response Concept Map
Instructions FOR TEACHERS

Make copies of the blank concept map. Have students complete the concept map to check their understanding of thehumoral response.
Each student should create a concept map of the humoral response. Depending on the familiarity of the students withconcept maps, you may choose to give the students the list of terms and have them create their own concept maps
and explain the connections for each term to the class.

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Evaluation Activity: The Humoral Response Concept Map
Fill in each oval using the appropriate vocabulary from the box below.

A type of phagocyte
which signals themature in the thymus andproduce cytokines that stimulate

are produced in the bonemarrow and give rise to

secreteremain in the body for years, enabling it to respond quickly and efficiently to the same antigen.

destroy

Plasma cells
Antigens
Memory T cells
Memory B cells
56

Macrophage
B cells
T cells
Antibodies

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Evaluation Activity: The Humoral Response Concept Map

KEY

Fill in each oval using the appropriate vocabulary from the box below.

Macrophage

A type of phagocyte
which signals the

T cells

mature in the thymus andproduce cytokines that stimulate

B cells

are produced in the bonemarrow and give rise to

Plasma cells

secreteMemory B cells

Memory T cells

remain in the body for years, enabling it to respond quickly and efficiently to the same antigen.

Antibodies

destroy

Antigens

Plasma cells
Antigens
Memory T cells
Memory B cells

Macrophage
B cells
T cells
Antibodies

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57

58

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BIOLOGICAL BODYGUARDS IMPLEMENTATION PLAN — WET LAB
Activity

Estimated
Time

Engagement:
HIV simulation activity
Note: This activity may bedone one day prior to the
ELISA test or in place of the
ELISA test.

20 minutes

Explanation of the ELISA test

5 minutes

ELISA test

60 minutes

Materials/Equipment
Centrifuge tubes labeled with numbers(one for each student)
30 mL of 0.1% NaOH (sodium hydroxide) for one student’s centrifuge tube
30 mL of water in each of the othertubes (one for each student)Label each tube with a number
Phenolphthalein to use as an indicator
One plastic pipette for each student
Index cards
Optional: Party hats, music
Transparencies
Materials described in ELISA prep section of this notebook or Bio-Rad’s ELISA
ImmunoExplorerTM Kit
Student data observation sheets
Focus question sheets

Closure: Analyze the results
to see which patient has HIV

5 minutes

Purpose/Objectives/
Essential Question

Purpose:To apply the specificity of antibodies
to a diagnostic test using the ELISA
technique.

Objectives:• To define a method of testing forHIV, when given models of antibodies and antigens• To perform an ELISA test to diagnose fictional patients for possible
exposure to HIV• To analyze the results of the ELISA

Essential Question:

Which of our patients’ sera has
antibodies that may be specific toHIV?

Student data observation sheets
Focus question sheets

Alignment with NC Competency Goals
Biology
Goal 1
Objectives 1.01, 1.02, 1.03, 1.04, 1.05
Goal 2
Objectives 2.01, 2.02, 2.03, 2.04
Goal 3
Objectives 3.01, 3.04
Goal 4
Objectives 4.01, 4.03, 4.04

Healthful Living
Goal 1
Objectives 1.02, 1.06
Goal 3
Objectives 3.01, 3.04, 3.07, 3.08, 3.09

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59Real-World Applications of ELISA:
Enzyme-Linked Immunosorbent Assay
Adapted from Bio-Rad’s ELISA Immuno Explorer KitTM Instruction Manualies. Variations of ELISA have been developed
Background
Over 100 years ago biologists discovered thatthe immune system of animals responds to theinvasion of foreign substances or antigens. A
quick and inexpensive test known as ELISA(Enzyme-Linked ImmunoSorbent Assay) is asensitive immunoassay that uses an enzyme
linked to an antibody or antigen as a marker
for the detection of a specific protein, especially an antigen or antibody. ELISA candetermine exposure to a particular infectious
agent, such as the human immunodeficiency
virus (HIV), the causative agent of AIDS (acquired immunodeficiency disease) by identifying antibodies present in the blood sample.
ELISA is widely used for tracking disease
outbreaks and detecting antigens and antibod-60

to allow for qualitative detection or quantitative measurement of either the antigen or theantibody. Qualitative responses result in a
Yes/No answer, can be obtained using ELISA,
and are definite and rapid. Quantitative results
can be measured because as the concentrationof the antibody or antigen increases, so does
the intensity of the blue color in the wells. The
blue color absorbs light at a specific wavelength and this absorbance can be measured
with a microplate reader.
ELISA is a powerful diagnostic tool in human
medicine. As you examine the table below,
you will see that the technique is used in avariety of other fields.

Human & veterinary medicine• Diagnose a variety of diseases, such as West Nile virus (in people and animals), HIV, SARS,
Lyme disease, trichinosis, tuberculosis, and many more by detecting serum antibodies

Veterinary• Detect viruses such as feline leukemia virus (FLV) and feline immunodeficiency virus(FIV) in cats
• Detect parasites, such as heartworms, in dogs
• Diagnose thyroid problems in dogs and cats by measuring serum thyroxine (T4)concentrations• Diagnose equine encephalitis in horses by detecting arboviruses

Agriculture:crops• Detect viruses, such as potato roll leaf virus and cucumber mosaic virus, in food crops• Detect mycotoxins in crops, such as aflatoxin in cereal grains and corn
• Detect viruses in decorative plants, such as bean yellow mosaic virus in gladiolus• Track adulteration of non-genetically modified (non-GMO) crops with GMO products(e.g., detecting Roundup Ready and Bt content)

Environmental• Test indoor air quality, such as detecting mold toxins in buildings

Food safety andquality• Prevent transmission of bovine spongiform encephalitis (mad cow disease, BSE) by
screening for central nervous system tissues in raw meat, in processed and cooked meats,
and on surfaces• Determine if food labeling is correct (e.g., by checking for cow milk proteins in goat
milk products or for non-durum wheat in durum wheat products)• Prevent allergic reactions by detecting ingredients that aren’t listed on food content labels (e.g., detecting peanuts in products in which peanuts are not listed as an ingredient)

Other• Detect restricted or illegal drug use (e.g., performance-enhancing drugs, marijuana,
methamphetamine, cocaine, etc.)• Confirm pregnancy by detecting human chorionic gonadotropin (hCG) in urine

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WET LAB Engagement ACTIVITY: HIV SIMULATION: TRACKING A DISEASE OUTBREAK
Note: This activity may be done one day prior to the ELISA test or in place of the ELISA test.

Materials• Transparency of the data on shared partners for the overhead• 50 mL centrifuge tubes with caps (one for each student)• Tap water• 0.1% NaOH (sodium hydroxide, 30 mL)• 3” x 5” cards (one for each student)• Plastic pipettes (one for each student)• Centrifuge tube with phenolphthalein

Pre-Lab Prep

1. Make up 30 mL of 0.1% NaOH for one centrifuge tube. Place one or two NaOH pellets in the tube.
2. Place 30 mL H2O in each of the other tubes (for the remainder of the students).
3. Label all tubes with a number. NOTE: Remember which tube contains the NaOH solution. Place all tubes in a
styrofoam holder.

INSTRUCTIONS FOR TEACHERS

1. Each student should receive a 3 x 5 index card, a plastic pipette, and a numbered centrifuge tube.
2. Instruct the students to “exchange” fluid with three other people, using the plastic pipettes to obtain fluid fromeach other’s tubes. Students should note on the 3 x 5 card the number of each tube with which they exchange fluid
and the order in which these fluid exchanges occur.
Remind students that it is important for them to exchange fluid and to turn the tube upside down to mix the solutions(with the cap on, of course). The point is to mix thoroughly between each exchange.
3. When three exchanges have been made, you can test the tubes for “HIV” by adding phenolphthalein to the solutions.
If the solutions turn pink, the tube has tested positive for “HIV.” If the solution remains clear, the tube has tested negative
for “HIV.” An alternative to phenolphthalein is phenol red. You will get either a pale pink color indicating “normal” (noinfection) or a bright violet color indicating a positive HIV test. An analysis can then be made to find out who had theoriginal vial of “HIV.” Students can start by working backward to find out who had the contaminated tube.
Students will be amazed by how many people get “HIV” from only three contacts.
This activity can be embellished by pretending that the students are going to a party and that they become exposedto the fluids of other people at the party. To set the mood, party music and hats should be available for use.
Note: Be sure to rinse tubes with vinegar before they are used for another class.

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61HIV SIMULATION: TRACKING A DISEASE OUTBREAK
INSTRUCTIONS FOR STUDENTS

1. Each person should receive a 3 x 5 index card, a plastic pipette, and a numbered centrifuge tube.
2. Using your plastic pipette, “exchange” fluid from the tubes of three other people. Note on the 3 x 5 card the number of each tube with which you exchange fluid and the order in which these fluid exchanges occur. It is important toexchange fluid and to turn the tube upside down to mix the solutions (with the cap on, of course). The point is to mix
thoroughly between each exchange.
3. After the three exchanges have been made, the instructor can test the tubes for “HIV.” If the solutions turn pink,
the tube has tested positive for “HIV.” If the solution remains clear, the tube has tested negative for “HIV.” An
analysis can then be made to find out who had the original vial of “HIV.” You can start by working backward to findout who had the contaminated tube.
4. If your numbered tube tested positive, record a “+” in the number column for your tube.
Or
If your numbered tube tested negative, record a “–” in the number column for your tube.

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HIV SIMULATION: tracking a disease outbreak class results
Make an overhead transparency of this page to use with the data of shared partners.

Sharing Partners (+ or -)Student #

1

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3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
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24

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biological bodyguards WET LAB
Purpose• To apply the specificity of antibodies to a diagnostic test using the ELISA technique.

Objectives• To define a method to test for HIV, when given models of antibodies and antigens.
• To perform an ELISA test to diagnose fictional patients for exposure to the HIV virus.
• To analyze the results of the ELISA.

EXPLANATION OF ELISA TESTIntroduce the investigation by telling students they will be given serum from two patients who are theoretically
being tested for HIV. They will test the patients for the presence of HIV antibodies. Before entering the lab, safety
procedures should be reviewed.

ELISA test

Each student will determine whether the patients test positive or negative for HIV. The results may be analyzed at
this time based on a qualitative analysis of color.

Evaluation

Ask each group what their diagnosis is for each patient. Encourage discussion by asking other groups whether theyagree or disagree. Ask students to explain their diagnoses.

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FOCUS QUESTIONS: ELISA
1. How does the immune system protect us from disease?

2. How do doctors use the immune response to protect you from disease?

3. How are antibodies made in your body?

4. What do the terms below mean?
a. AIDS

b. HIVc. ELISA

d. Opportunistic infection

5. What are the characteristic ways that a person can get HIV?

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ANSWERS TO FOCUS QUESTIONS: ELISA
1. How does the immune system protect us from disease?
The innate immune system includes physical barriers (e.g., the skin and mucous membranes that prevent pathogens from entering the body) and cellular responses (e.g., circulating macrophages that respond to foreign invaders). Our acquired immune system mounts a specific antibody response upon exposure to a foreign invader,and our immune cells attack the foreign invader.
2. How do doctors use the immune response to protect you from disease?
Doctors use the immune response when we are vaccinated against disease. Our immune system remembers
diseases we were exposed to and the next time we are exposed to the disease our immune system attacks thedisease more quickly and efficiently. Doctors take advantage of this priming effect by exposing us to inactivateddiseases (either killed or weakened organisms that cannot make us sick) so that if we are later exposed to thedisease our body will mount a strong and immediate antibody response, reducing or eliminating the chance thatthe disease will make us sick.
3. How are antibodies made in your body?
Antibodies are produced in response to specific antigens. B cells produce antibodies.
4. What do the terms below mean?
a. AIDS
Acquired Immunodeficiency Syndrome — the stage of the disease when the characteristic symptoms appear, and CD4+ T cell count drops.
b. HIV
Human immunodeficiency virus — the virus that causes AIDS
c. ELISA
Enzyme-linked immunosorbent assay — the first test that doctors use to detect HIV
d. Opportunistic infection
An infection by an organism to which a healthy body would normally be resistant
5. What are the characteristic ways that a person can get HIV?
Sexual contact, transfer of infected body fluids to a non-infected person

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KEYEXPLANATION OF ELISA TESTIntroduce the wet lab by telling students they will be given serum from two patients who are theoretically being
tested for HIV. Choose from any of the two patients listed below. The students will test the patients for the presenceof HIV antibodies. Before entering the lab, safety procedures should be reviewed.

BIOGRAPHICAL SKETCHES
Sample A

Bill C.		
Age 40		
Sex M
Occupation: Transient, lives on the streets
Time after possible exposure: unknown
Reason to suspect HIV infection: Appears to be a habitual drug user. Has “needle tracks” on both arms. He
denies using intravenous drugs. Is attempting to donate
blood to a blood bank in the inner city.

Sample C

Roger T.
Age 15		Sex M
Occupation: High school student
Time after possible exposure: 3 years to present
Reason to suspect HIV infection: He has just learned
that his older brother has AIDS. Fears that he may havebeen infected due to frequent contact from sharing same
bedroom, bathroom, and eating utensils. Insists onbeing tested for HIV.

Sample E

Norma T.
Age 36		
Sex F
Occupation: Policewoman
Time after possible exposure: 4 months
Reason to suspect HIV infection: While making anarrest, she was scratched, bitten, and spat upon by aperson claiming to be HIV positive.

Sample G

Lucy L.		
Age 33		Sex F
Occupation: HomemakerTime after possible exposure: 7 years to present
Reason to suspect HIV infection: Her husband wasformerly heavily involved in a promiscuous lifestyle.
He tested positive for HIV before their marriage, andthey have taken all recommended precautions to protect
her from contracting the disease. However, she has
recently heard of a Center for Disease Control reportstating that the virus can be transmitted by kissing, if
the person with HIV has bleeding gums. Her husband
has the early stages of gum disease.

Sample B

Amy B.		
Age 26		
Sex F
Occupation: Elementary school teacher
Time after possible exposure: 6 months
Reason to suspect HIV infection: Assisted a student who
fell off playground equipment and cut his head. Amy was
not wearing protective gloves and noticed the scratches on
her hand she had received from weeding her garden.

Sample D

John K.		
Age 17		Sex M
Occupation: High school student
Time after possible exposure: 0 months
Reason to suspect HIV infection: Has recently begun
dating a fellow student seriously. He and his new partner
have agreed to be tested before becoming sexually active.

Sample F

Susan J.		
Age 25		Sex F
Occupation: Nurse
Time after possible exposure: 3 months
Reason to suspect HIV infection: While she wasworking with an AIDS patient, a hypodermic needle
punctured her latex glove.

Sample H

Tom M.		
Age 25		Sex M
Occupation: Computer Programmer
Time after possible exposure: 10 years
Reason to suspect HIV infection: Has had persistentinfections and has been in generally poor health overthe last few months. Has had a few homosexual relationships in the past and is currently in a monogamous
homosexual relationship.

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WET LAB PROTOCOL: ELISA ANTIBODY TEST

From Bio-Rad’s ELISA Immuno Explorer Kit Instruction Manual
1. Label the yellow tubes (if necessary) to identify the
samples being tested.
2. Label your 12-well strip. On each strip label the first threewells with a “+” for the positive controls and the next threewells with a “-” for the negative controls. Label the remaining wells to identify the samples being tested (three wellseach).
3. Use a fresh pipet tip to transfer 50 μl of purified antigen(AG) into all 12 wells of the microplate strip.
4. Wait 5 minutes for the antigen to bind to the plastic wells.
5. WASH:a. Tip the microplate strip upside down onto the paper
towels, and gently tap the strip a few times upside down.
b. Discard the top paper towel.
c. Use a transfer pipet to fill each well with wash buffer.
d. Tip the microplate strip upside down onto the paper
towels and tap.
e. Discard the top 2-3 paper towels.
6. Use a fresh pipet tip to transfer 50 μl of the positive control (+) into the three “+” wells.
7. Use a fresh pipet tip to transfer 50 μl of the negative control (-) into the three “-” wells.
8. Transfer 50 μl of each of your team’s serum samples into
the appropriately initialed three wells, using a fresh pipet tip
for each serum sample.
9. Wait 5 minutes for the antibodies to bind to their targets.
10. Wash the unbound primary antibody out of the wells by
repeating all of wash step 5.
11. Use a fresh pipet tip to transfer 50 μl of secondary antibody (SA) into all 12 wells of the microplate strip.
12. Wait 5 minutes for the antibodies to bind to their targets.
13. Wash the unbound secondary antibody out of the wellsby repeating wash step 5 two times.
14. Use a fresh pipet tip to transfer 50 μl of enzyme substrate(SUB) into all 12 wells of the microplate strip.
15. Wait five minutes. Observe and record the results.
+ + + –68

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NAME _________________________

Data/Observation Sheet
1. During this lab, you are testing for the presence of ______________________ in a patient’s serum.
2. A positive ELISA test would occur assuming each of the molecules below interacted accordingly. Label eachmolecule in the diagram below:

A. Secondary Antibody
B. Primary Antibody
C. Enzyme
D. Substrate
E. Antigen

3. What is the function of the secondary antibody?
4. What is the function of the viral extract in this assay?
5. In a patient who is HIV negative, which molecule would be missing from the ELISA test?
6. Why did you assay your samples in triplicate (three times)?

RESULTS

Indicate which wells below exhibited a blue color by shading the appropriate well(s).

Positive control

Negative control

Patient A

Patient B

7. Which patient tested positive for HIV? 							Note: A positive result using ELISA would need to be confirmed with a Western blot prior to diagnosing apatient with HIV.
8. Does a positive HIV test mean that this patient has AIDS? Explain your answer.

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69

Data/Observation Sheet

KEY

1. During this lab, you are testing for the presence of antibodies to HIV in a patient’s serum.
2. A positive ELISA test would occur assuming each of the molecules below interacted accordingly. Label eachmolecule in the diagram below:

D
A
B

C
A. Secondary Antibody
B. Primary Antibody
C. Enzyme
D. Substrate
E. Antigen

E

3. What is the function of the secondary antibody?
To recognize and bind to the primary antibody. In this case, the primary antibody is specific for HIV.
4. What is the function of the viral extract in this assay?
To provide the antigen to which the primary antibody can bind. A simulated HIV viral extract is used in this assay.
5. In a patient that is HIV negative, which molecule would be missing from the ELISA test?
The primary antibody would be absent from a patient who is HIV negative.
6. Why did you assay your samples in triplicate (three times)?
This represents another experimental control, since the results for all three wells for a particular patient shouldbe the same. If the same result is not achieved for all three wells, this indicates an experimental error.

RESULTS

Indicate which wells below exhibited a blue color by shading the appropriate well(s).

Positive control

Negative control

Patient A

Patient B

7. Which patient tested positive for HIV? 							Patient A is HIV positive.
8. Does a positive HIV test mean that this patient has AIDS? Explain your answer.
A positive HIV test does NOT mean that an individual has AIDS. An HIV positive patient is clinically diagnosed with AIDS if two criteria are met: 1) the presence of one or more AIDS indicator illnesses (opportunistic
infections) and 2) a TH cell count below 200 cells/µl.

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Equipment Needed for Biological Bodyguards Wet Lab
VendorCatalog Number

Item

Unit

Minimum
Needed

Price

TOTAL

REQUIRED EQUIPMENT
Bio-Rad166-0507EDU

20-200 digital micropipet

1$159.00

8$1272.00

EQUIPMENT TOTAL $1272.00
REQUIRED CONSUMABLES
Bio-Rad166-2400EDU

ELISA Immuno Explorer Kit

1 kit$99.99½ kit$49.50

Bio-Rad223-9347EDU

Racked pipet tips TBR-35 tips

1 box of
1,000

$35.2064 tips$2.26

CONSUMABLES TOTAL $134.20
Approximate price per class of 24 students/8 student groups $51.76
OPTIONAL EQUIPMENT
Bio-Rad166-0501EDU

Mini incubation oven1$295.00

Bio-Rad166-0504EDU

Water bath1$505.00

Carolina
Biological21-5570

Micro-test tube rack, polypropylene

1

$4.00

Bio-Rad166-0709EDU

Rocking platform

1$575.00

Microwave oven

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BIOLOGICAL BODYGUARDS IMPLEMENTATION PLAN — POST-LAB
Activity

Estimated
Time

Materials/Equipment

Biological Bodyguards
Quiz Game

20 minutes

Questions and answers provided in
notebook or on CD

Post-lab focus questions

15 minutes

Copies of post-lab focus questions

Purpose/Objectives/
Essential Question
Purpose:To analyze the results of the ELISA
test to see which patient/patients
may have HIV

Objectives:
Homework assignment:
Investigate one of the proposed theories concerning
the body’s immune system
Video: An Inside Look:
The Flu(Discovery Channel School)

30 minutes

Copies provided in notebook and on CD

27 minutes

Video (www.discovery.com,
Item# 745042)• To analyze the results visible on thetest plate• To successfully explain the diagnosisof each patient tested

Essential Question:

Which of our patients’ sera has
antibodies that may be specific tothe HIV virus?

Alignment with NC Competency Goals
Biology
Goal 1
Objectives 1.01, 1.02, 1.03,1.04 1.05
Goal 2
Objectives 2.01, 2.02, 2.03, 2.04
Goal 3
Objectives 3.01, 3.04
Goal 4
Objectives 4.01, 4.03, 4.04

Healthful Living
Goal 1
Objectives 1.02, 1.06
Goal 3
Objectives 3.01, 3.04, 3.07, 3.08, 3.09

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73Biological Bodyguards Quiz Game Questions
ImmuneSystemPlayers

Biological
Bodyguards

Fact or Fiction:
The only way tofight disease is
by using medication.

Which molecule
acts as the foreign invader,stimulating yourbody’s immune
response?

Fact or Fiction:
The only way
your body develops acquired
immunity fora disease is bycontracting thatdisease.

Fact orFiction

200

400

600

800

1000

74

Hodge
Podge

ELISA

Diseases

The ELISA in the
wet lab tested
for possible exposure to what
antigen?

When performing the ELISA
during the wetlab, why did
you test three
replicates ofeach sample?

True or False:
All bacteriacause diseases
in humans andshould therefore
be eliminated.

What is theshape of an
antibody?

Which cells act
as scouts, engulfing antigens
and presenting
them to specificwhite blood cells
for identification?

What was thefunction of theviral extract inthe wet lab?

If you test
positive for an
antibody using
ELISA, does thatmean that you
definitely havebeen exposed tothe antigen?

What does AIDS
stand for?

What does HIV
stand for?

Fact or Fiction:
Your body has
a “memory”
for antigens,allowing for aquicker immune
response.

What is thename of thewhite blood
cells that act as
the intelligenceagent, signalingother cells to attack the foreign
invaders?

What do we callan infection by
an organism towhich a healthy
body normally
would be resistant?

Other than testing for exposure
to HIV, what
other ways is
ELISA used?

What is the difference between
HIV and AIDS?

Name two bodyparts that act
as physical barriers to prevent
pathogens fromentering thebody.

Fact or Fiction:
T cells areproduced in thethymus.

What is the term
for white blood
cells that giverise to plasma
cells, which create the antibodies necessary todestroy invaders(antigens)?

Based on the
wet lab, dideither of thepatients possibly have theantibodies for
HIV? Explain.

What does ELISA
stand for?

Aside fromyour immune
response, list 3
ways your bodyresists acquiring
diseases.

During the wetlab, why did you
make positive
and negative
control wells?

Fact or Fiction:
In order for an
immune system
to completely
prevent a
disease, thebody must havebeen previously
exposed to theantigen thatcauses thatdisease.

What cells record
the characteristics of theantigen so thatthe B cell will
immediately be
activated thenext time that
antigen invades?

Assume you area doctor and you
performed an
ELISA test on apatient to testfor HIV. The test
returned a positive result. Whatdo you tell yourpatient?

Explain the stepsof an HIV ELISA
test (such as thatused in the wetlab) and describe
the results you
would expect
to find when
testing a patient
who is positive
for the antibody.

What are vectors? Define andgive examples.

What are threecommon waysthat HIV istransmitted?

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Biological Bodyguards Quiz Game ANSWERS

200

400

Fact orFictionImmuneSystemPlayers

Fiction. Your body’s
immune system is able
to fight off disease
without medication.

Antigens. Examples
of antigens include
viruses, bacteria, andpollen.

Fiction. Vaccines
stimulate an acquired
immunity without
actually giving you thedisease.

Biological
Bodyguards

1000

Hodge
Podge

ELISA

Diseases

HIV virus.

By triplicating the test,
you will be better able
to know if the results
are accurate.

False. A relative few
bacteria actually cause
disease; many others
are actually very
useful.

Antibodies are Yshaped.

Macrophages.

It contained theantigen to which theprimary antibody, if
present, could bind.

Not necessarily.
Further tests should
be given (i.e., Western
blot, immunoblot).

Acquired ImmunoDeficiency Syndrome.

Human
Immunodeficiency
Virus.

Fact. Memory B
cells recall familiar
antigens.

T cells.

Opportunistic infection.

Test for pregnancy,
drug use (marijuana,
cocaine).

HIV is the virus thatcauses AIDS. AIDS is
only diagnosed if two
criteria are present:
1) one or more AIDS
indicator illnesses(opportunistic infections) and 2) a Helper
T cell count below 200
cells/microliter. It cantake 10+ years for HIV
to develop into AIDS.
During this time, aninfected person can stilltransmit HIV to others.

Skin and mucous
membranes.

Fiction. T cells areproduced in the bonemarrow, and mature in
the thymus.

B cells. The B cells
act as the weapons
expert.

Yes, patient A. That
assay turned out
blue like the positive
control.

Enzyme Linked ImmunoSorbent Assay.

Skin, mucous membranes, and internal
body temperature act
as barriers to infection.

Controls are used tomake sure the test
works properly.

Fiction. You are bornwith what is called
innate immunity. The
four components ofthis are anatomicalbarriers (skin, etc.),
physiological barriers(body temp too highfor some bacteria tolive), phagocytic barriers, and inflammatory response which
destroy new infectious
cells.

Memory B cells.
Because our bodies
have these cells,
our immune systemquickly responds tofamiliar antigens.

The test came backpositive, meaning thatthe patient may havethe virus. A further
test, the Western
blot, must be run todetermine if HIV isdefinitely present
and to eliminate thepossibility of a false
positive. In case it isHIV, the patient shouldtake steps to preventthe spread of HIV toothers until the final
results are in.

1. Place antigen (suchas HIV) into 3 wells;
the antigen will attach
to the wells. 2. Placepatient’s serum into
wells; in a positive
patient, a primary
antibody will bind to
the antigen. 3. Place
secondary antibodies
into wells; in a positive
patient, these will bindto primary antibodies.
4. Place enzyme
substrate into wells; ina positive patient, thiswill bind to secondary
antibodies, creating a
blue color. If negative,no binding or color
change will occur.

Organisms that carrypathogens from one
host to another (bacteria, viruses, ticks,
mosquitoes).

HIV is transmitted innumerous ways, suchas sexual activity,
sharing hypodermic
needles with aninfected person, andfrom mother to baby
during birth andbreastfeeding.

600

800

KEY

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75

POST-LAB FOCUS QUESTIONS
From Bio-Rad’s ELISA Immuno Explorer™ Kit Instruction Manual
1. Did your serum have antibodies to the disease?

2. If you tested positive for antibodies, does this mean that you have been exposed to the disease?

3. What reasons could there be for a positive test when you actually do not have the disease?

4. Why did your assay include three replications of each sample?

5. When you added serum samples to the wells, what happened to the serum antibodies if the serum sample waspositive? What if it was negative?

6. Why did you need to wash the wells after every step?

7. When you added secondary antibody, what happened if your serum sample was positive? What if the serum
sample was negative?

8. What ELISA-type tests can you buy at your local pharmacy?

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POST-LAB FOCUS QUESTIONSKEY

From Bio-Rad’s ELISA Immuno Explorer™ Kit Instruction Manual
1. Did your serum have antibodies to the disease?
Students explain using data from their results.
2. If you tested positive for antibodies, does this mean that you have been exposed to the disease?
A positive result does not necessarily mean that you have been exposed to the disease.
3. What reasons could there be for a positive test when you actually do not have the disease?
It could be a false positive. Not all assays are specific for a single disease agent. For example, the ELISA for
exposure to Lyme disease, which tests for IgG and IgM against the bacteria that cause the disease, has only
72% specificity, and a positive ELISA must be confirmed by a more specific test such as a Western blot or an
immunoblot.
Another cause of false positives is past exposure to a disease. For example, most adults have been exposed to
Epstein-Barr virus (EBV; the cause of many, but not all, cases of mononucleosis), and some people maintainlevels of antibodies to EBV for years after clearing the disease. If they present to their physician with a feverand sore throat, they may test positive for EBV, but EBV may not be the cause of their symptoms.
A third cause of false positives is experimental error, such as putting a positive control into a well where you
thought you were putting an experimental sample.
4. Why did your assay include three replications of each sample?
Assaying the samples in triplicate is another control. If you do not get the same result in all triplicate wells, youhave a problem with your experimental technique or you have made a pipetting error. In a clinical laboratory,
the experiment would have to be repeated.
5. When you added serum samples to the wells, what happened to the serum antibodies if the serum sample waspositive? What if it was negative?
If the sample was positive, serum antibodies that recognized the purified antigen in the wells bound to the antigen. If the sample was negative, no antibodies bound.
6. Why did you need to wash the wells after every step?
Washing removes any proteins that have not bound to the plastic wells and any antibodies that have not bound totheir targets, thus preventing unbound proteins (either antigen or antibodies) from giving false positive results.
7. When you added secondary antibody, what happened if your serum sample was positive? What if the serum
sample was negative?
If the sample was positive, the secondary antibody bound to the serum antibodies that were bound to the purified
antigen adsorbed to the wells. If the sample was negative, there were no serum antibodies bound in the wells
and therefore the secondary antibody had nothing to bind to and was washed away.
8. What ELISA-type tests can you buy at your local pharmacy?
Test kits that are based on the same principles as the ELISA include home pregnancy and ovulation tests, andtests for the presence of illegal drugs such as marijuana and cocaine.
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77

VIDEO COMPREHENSION QUESTIONS: An Inside Look: The Flu
From DiscoverySchool.com
1. What happens immediately after viruses and bacteria enter the body?

2. How does a virus take advantage of the way human cells work?

3. Why does the entire body rather than just the throat experience flu symptoms?

4. How does a T cell become activated, and what happens immediately after it’s been called into duty?

5. What are antibodies, and what is their role in fighting the flu?

6. What causes immunity to the flu?

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ANSWERS to VIDEO COMPREHENSION QUESTIONS: An Inside Look: The Flu

KEY

From DiscoverySchool.com
1. What happens immediately after viruses and bacteria enter the body?
When viruses and bacteria first enter the body through the nose, they encounter the hairs lining the nostrils.
These hairs trap nearly every particle that’s inhaled, and they contain mucus that dissolves bacteria. A virus may
survive, however, if it becomes detached from a nose hair and is sucked deeper into the nose. From the back of
the nose, the virus can either go to the stomach, where it will be destroyed, or make its way to the throat, beginning the process of giving the person the flu.
2. How does a virus take advantage of the way human cells work?
It impersonates one of the proteins that cells use to communicate with each other. A cell can therefore be fooled
into thinking the virus is a harmless protein and will permit the virus to enter it. Once inside the cell, the virus
begins to use the cell’s structure to manufacture components for new viruses.
3. Why does the entire body rather than just the throat experience flu symptoms?
As the flu viruses multiply, macrophages in the throat release interleukins, which are chemicals that go throughthe bloodstream to summon reinforcements to the throat. The interleukins cause nerves to be hypersensitive,
making even slight touches uncomfortable. They also raise the body’s temperature to make it a less hospitableenvironment for the virus. This temperature increase tricks the body into feeling cold. Blood vessels around thebrain swell, causing a headache. All of these symptoms help remind the flu victim to slow down so that energy
can be channeled into defeating the virus.
4. How does a T cell become activated, and what happens immediately after it’s been called into duty?
Dendritic cells gather fragments of the flu virus and then search the body’s lymph glands for an appropriate T
cell. Once this T cell has been located, it begins to divide. The new T cells then move to the throat through thebloodstream and selectively destroy the infected throat cells.
5. What are antibodies, and what is their role in fighting the flu?
Antibodies are tiny proteins manufactured by B cells. They lock onto the spikes of newly produced viruses,
paralyzing the viruses and preventing them from infecting new cells.
6. What causes immunity to the flu?
Some T cells remain as memory cells, patrolling the body for the rest of the person’s life. If the virus tries toenter the body again, these memory cells will instantly wipe it out, unless it has mutated.

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79

HOMEWORK ASSIGNMENT
Student Objectives• Determine the basis for scientific theories• Address this question: do scientific theories change over time?
Listed below are several theories that have been proposed concerning the body’s immune system:• 1st century belief that the cause of disease was magical or divine in source• Cause of disease tinged with Old Testament morality and belief• 1700s — Edward Jenner’s smallpox vaccination• Louis Pasteur’s germ theory of disease• Eating your way to immunity• Smoking and depression of the immune system• Immunity associated with vaccinations• Exercising your way to immunity• Robert Koch and Koch’s Postulates• Viral mutation/evolution• Resistant strains of bacteria
Using the media center and/or the Internet, research one of these theories to discover:• the evidence or beliefs on which the theory was founded.
• if your chosen theory would be considered valid based on scientific evidence today.
• if there is a need for further research to verify or validate your theory.
Report back to the class on your findings.

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BIOLOGICAL BODYGUARDS IMPLEMENTATION PLAN — ADDITIONAL ACTIVITIES & RESOURCES
Materials/Equipment

Subjects
CoveredSuggestions

90 minutes

Access to the Internet or media center; computer access for pamphletproduction

English, AP Biology, Allied
Health I and II, HealthOccupations, Medical Sciences I & II, Anatomy andPhysiology

Located in notebook

60 minutes

Human chorionic gonadotropin(HCG) CBS #BA85-4240
Home pregnancy tests (Ask pharmacist for outdated kits or available at
The Dollar Store)

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

Arousing the Fury
located in notebook

AIDS: The Effect on the Immune Response
Graphing activity comparing the normal immune
response to an AIDS-infected immune response

90 minutes

Copies of 2-page worksheet for each
student
2 sheets graph paper per student
Optional: Excel

Mathematics

Located in notebook

ELISA Antibody TEST, Flash Animation

5 minutes

Access to the Internet
www.tracy.k12.ca.us/thsadvbio/
biorad/ELISAwonderflash.swf

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

Activity
Deadly Disease among Us:
Pamphlet on a Disease Scoring Rubric
Students select and research a disease, design an
instructional pamphlet, and present it to the class.

Lab: The Sensitivity Range of a Home Pregnancy
ELISA Test for Human Chorionic Gonadotropin

Your World: Biotechnology and You — AIDS issue

Immune System Animations. These include
T cell, B cell, and machrophage animations.

Protecting the Herd
NIH Curriculum Supplement Series

Superbugs: An Evolving Concern
NIH Curriculum Supplement Series

Deadly Diseases Among Us
NIH Curriculum Supplement Series

Estimated
Time

AIDS issue provided inworkshop. Your World isalso available to download for free at www.
biotechinstitute.org/
resources/your_world_
magazine.html

30-60 minutes

Many activities in teacher’s guide
Magazine and activities for class

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

20 minutes

Access to the Internet
http://highered.mcgraw-hill.com/
sites/0072919183/student_view0/
chapter39/elearning.html

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

90 minutes

Make copies for students ortransparencies of materials

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

Available for free atscience.education.nih.
gov/customers.nsf/
HSDiseases?OpenForm

90 minutes

Copies of Bacterial Growth Experiment

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

Available for free atscience.education.nih.
gov/customers.nsf/
HSDiseases?OpenForm

30 minutes

Causes of death quiz (transparency)
Set of disease cards for each groupof 5 students

AP Biology, Allied Health I
and II, Health Occupations,
Medical Sciences I & II,
Anatomy and Physiology

Available for free atscience.education.nih.
gov/customers.nsf/
HSDiseases?OpenForm

Additional Resources:
cellsalive.com
www.biointeractive.org
www.accessexcellence.org
www.hhmi.org/news/schatz.html
www.cancer.gov/cancertopics/understandingcancer/immunesystem
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81DEADLY DISEASE AMONG US: PAMPHLET ON A DISEASE
Assignment: Select and research one disease from the list below or one of your own and prepare an instructional
pamphlet to present to the class.

scoring rubric
1 - Criterion: Quality of Research
12

1 source3

4

3 sources

5
5 sources

2 - Criterion: Question and Answer
1

2

Many factual errors

3

4Some factual errors

5
No factual errors

3 - Criterion: Graphics
1

2

3

4

Graphics that describe
the disease

No Graphics

5
Graphics that instruct
as well as dazzle!

4 - Criterion: Organization
1

2

Little evidence ofdesign and planning3

4

Some evidence ofdesign and planning

5
Strong evidence ofdesign and planning

5 - Criterion: Oral Presentation
1

2

Did little to describe
disease, symptoms,
cause, and cure3
Explained disease,symptoms, cause, andcure adequately

4

5
Grabbed everyone’s
attention

Examples of types of diseases to select from are: AIDS, cholera, Creutzfeldt-Jakob Disease (CJD), Ebola, Guinea
worm disease, influenza, Legionnaire’s disease, Lyme disease, malaria, strep throat, plague, pneumonia, polio, schistosomiasis, tuberculosis, anthrax, smallpox.

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ELISA Additional Lab Activity
The Sensitivity Range of a Home Pregnancy ELISA Test for Human Chorionic Gonadotropin (HCG)
detect the anti-HCG antibody that will bind to the HCG
Objectives

Students will gain knowledge of the process for screening human urine to detect the presence of human chorionic gonadotrophin, commonly known as HCG, using
the ELISA technique of immunological assay.

in the urine. This complete HCG concept is the basis forhome pregnancy tests. Most home pregnancy tests willdetect the HCG concentration levels in the very early
weeks of pregnancy due to the rapid increase of thishormone (see data table below).

Background Information

ELISA is a very common immunological assay used inlabs, as well as the privacy of homes, across the country
today. This process can even detect horse meat in
hamburger and antibiotics in milk. However, probably
the most important application of this technique is in
the clinical setting. ELISA is an important tool in thescreening for HIV exposure, as the basis for pregnancy
tests, and in ovulation predictor testing, which are allbased on the binding ability of antibodies.
Rather than testing for the presence of a condition or antigen
itself, ELISA tests for the presence of antibodies specific to thecondition or antigen of interest.
This relies on antibodies’ propertyof binding to specific antigens
Primary
and/or to other antibodies. KnowAntigen antibody
ing which antibody binds to whichantigen (see diagram) allows a search for an antigen bysearching for the antibody that responds to it.
Therefore, when an individual is tested for HIV, the labtechnician does not screen the blood for HIV, but for
the antibodies to HIV. If HIV antibodies are detected in
the blood, one can conclude that exposure to HIV has
occurred.
Another familiar use of this ELISA technique is in homepregnancy-testing kits. The antigen known as humanchorionic gonadotrophin (HCG), is detected in thesekits. HCG is a hormone that is secreted in bodily fluidsof a female during pregnancy. The responsibility ofthis hormone is to prevent the destruction of the corpus
luteum at the end of the menstrual cycle. With the presence of HCG, the corpus luteum also begins to secretemassive amounts of estrogen and progesterone hormones. These hormones are responsible for stimulating
the endometrial lining of the female uterus to grow andstore adequate amounts of the nutrients needed for fetal
development. HCG can then be detected in the urine of
the mother soon after the fertilized embryo implants itself into the endometrial lining of the uterus. ELISA can

Week of Pregnancy

Amount of HCG in Urine(mIU/mL)3

5 – 504

3 - 4265

19 – 7,340

6

1,080 – 56,500

7-8

7,650 – 229,000

9-12

25,700 – 288,000

13-16

13,300 – 254,000

17-24

4,060 – 165,400

25-40

3,640 – 117,000

Essential Question

What is the sensitivity range of a home pregnancy
ELISA test for human chorionic gonadotropin?

Materials Needed• Vial of 10,000 international units (IU) of dried HCG(available through Carolina Biological Supply Company)• 200 mL tap water• Yellow food coloring• 4 “stock bottles” – or comparable containers• Home pregnancy test kit (available at pharmacy
stores, as well as the Dollar Store)• Small bottle large enough for 5 mL (one bottle foreach group of students)

PRE-LAB TEACHER PrepARATIONS

1. Reconstitute the entire vial of dried HCG by adding
200 mL tap water. Mix completely dissolving the HCG.
The stock concentration of HCG is now 50 IU per mL.

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83

2. Add enough yellow food coloring so the mixture
resembles dark urine.

4. After reviewing the class results, answer the following questions for this activity.

3. Using tap water, prepare dilutions of the stock solution using the formula C1V1 = C2V2.
C1 = stock concentration of 50 IU/mL
C2 = diluted concentration
V1 = 200 mL of stock concentration
V2 = 2 mL (approximate – check the directions on
the pregnancy test kit to determine the volume of “urine” needed for the test)a. How reliable is this test?

b. Is it more likely to give positive or false negative
results? Why?

4. Dilute a set of samples within the range of detectablelevels of HCG in the third week of pregnancy as shownin the previous chart.

c. What factors might contribute to incorrect (false
positive or false negative) results?

5. Provide each lab team with 2 mL of a different
dilution representing the “urine” to be tested.

INSTRUCTIONS FOR STUDENTS

Each lab team will be testing a different concentrationof “urine.”		

5. As a lab team, draw an illustration of how ELISA
might work in these kits. For example, what might be
the components of each of the reagents provided in thetest kit?

1. Follow the directions in the test kit to test your“urine” sample for the presence of HCG. The sample
has been prepared in advance by your teacher.

Going Further

2. Record your lab group’s results in the provided
space:Have students investigate the accuracy of outdated
home pregnancy kits in comparison to kits that are current.

______________________________Have students compare different test kits with the same
concentration levels.

3. Report your results to the teacher. All groups willenter their data into the Class Data Chart below by lab
group number.

CLASS DATA CHART BY LAB GROUP
#1

84

#2

#3

#4

#5

#6

#7

#8

#9

#10

#11

#12

#13

#14

#15

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NAME ______________DATE ______________CLASS ______________

AIDS: The Effect on the Immune Response
Background

Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by the human immunodeficiency virus (HIV)and results from the destruction of an individual’s immune system. HIV is passed from one person to another when
infected blood, semen, or vaginal secretions come in contact with an uninfected person’s broken skin or mucous
membranes. Infected pregnant women can pass HIV to their babies during pregnancy or delivery, as well as throughbreast-feeding. People with HIV have what is called an HIV infection. Some of these people will develop AIDS as aresult of their HIV infection.

How does HIV destroy the immune system?

The body’s immune response involves white blood cells called lymphocytes. The two main kinds of lymphocytes
involved in the immune response are T cells and B cells. Certain types of T cells destroy antigens directly. B cells
produce antibodies with the help of other kinds of T cells known as TH cells (for helper). When HIV enters the body,the virus destroys the TH cells that facilitate the production of antibodies. Therefore, the immune system’s ability tofight disease causing pathogens is impaired. The criteria for AIDS diagnosis is a TH cell count below 200 cells/μl.
The person usually dies from accumulation of secondary infections called opportunistic infections. Some examples
include tuberculosis, P. carinii, and Karposi sarcoma.

Student Objectives• Plot data in graph form to demonstrate a healthy body’s normal immune response.
• Plot data in graph form to demonstrate an HIV-infected body’s immune response.
• Compare and interpret these two different immune responses.

Materials• colored pencils (red, blue, green, and yellow)• graph paper (1 sheet)

Procedure: Part A. The Normal Immune Response

Tables 1 and 2 refer to hypothetical numbers of microbes and immune response (units). Immune response (units)summarizes all the activities of the immune system, including antibody production and direct attack on invaders.
1. Examine Table 1, Normal Immune Response.

TABLE 1: NORMAL IMMUNE RESPONSE
MonthsNumber of Microbes

Immune Response (units)

0
3
6
36
48
60
72
84
96
108
120

1
1,000
10,000
1,000
10
1
0
0
0
0
0

0
0
1
100
1,000
1,000
1,000
100
10
1
1

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85

2. Follow these steps to construct a graph of the data in Table 1 located above:• Label the vertical axis (Y-axis) “Number of Microbes.” Using an appropriate scale, number the Yaxis from 1 to 100,000.
• Label the horizontal axis (X-axis) “Number of Months.” Using an appropriate scale, number the Xaxis from 0 to 120.
• Use a red pencil to plot the number of microbes against the number of months.
• Use a blue pencil to plot the immune response (units) against the number of days.
• Be sure to give your graph a title and provide a key indicating the color code.

TABLE 2: IMMUNE RESPONSE IN PERSON WITH HIV
MonthsNumber of Microbes

Immune Response (units)

0
3
6
36
48
60
72
84
96
108
120

1
1,000
100,000
10
1
1
1
10
100
1,000
100,000

150
1,000
10,00010,000
1,000
500
100
1
0
0

4. On the same sheet of graph paper, include the data from Table 2 located above:• Use a green pencil to plot the number of microbes against the number of months.
• Use a yellow pencil to plot the immune response (units) against the number of months.

Student Analysis

Use your graph of the Normal Immune Response to answer the following questions.
1. What happens to the number of microbes:
during the first 3 months? ____________________________________________________________________
during months 6 through 60? _________________________________________________________________
2. What happens to the immune response:
during the first 3 months? ___________________________________________________________________
during months 6 through 60? _________________________________________________________________
3. Summarize in 2-3 sentences what happens during a normal immune response.
_______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________86

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Use your graph of the Immune Response of a Person with HIV to answer the questions below.
4. What happens to the number of HIV:during the first 3 months? _____________________________________________________________________
during months 6 through 60? __________________________________________________________________
during months 72 through 120? ________________________________________________________________
5. What happens to the immune response in a person with HIV:during the first 48 months? ___________________________________________________________________
during months 60 through 120? ________________________________________________________________
6. Summarize in 2-3 sentences what happens during the immune response in a person with HIV.
_______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________
Compare and Contrast:
7. How do the time periods in the two graphs differ? __________________________________________________
8. How is the HIV graph similar to that of the normal immune response? _____________________________________________________________________________________________________________________________________________________________________________________________________________________________
9. How is the HIV graph different from that of the normal immune response? _________________________________________________________________________________________________________________________________________________________________________________________________________________________
10. How do you explain the increase in the number of HIV viruses during months 84 through 120? ________________________________________________________________________________________________________________________________________________________________________________________________________
Further Research: Find out some of the other diseases that affect the immune system.

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87

88

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Social Studies

X

ScienceX

MathHealthUsing Drugs? You’re in Trouble

EnglishActivityArts

BIOLOGICAL BODYGUARDS IMPLEMENTATION PLAN — INTERDISCIPLINARY BRIDGES

X

X

Activity sheet

X

One copy of handout per student, or accessto internet.
www.state.gov/s/gac/rl/or/c11652.htm

X

Copies from notebook or CD. Internet accessfor research of diseases. PowerPoint access, if
available, for student presentations

X

3 Handouts (attached): Engagement Activity,
FAQ and Glossary (Understanding Clinical
Trials), Exploration Activity (choose either“Strategies for Delivering Anti-HIV Therapy
in South Africa” or “Safety of and Immune
Response to a Bird Flu Virus Vaccine in Healthy
Adults”)
Optional website: ClinicalTrials.gov.

X

List of related music and literature“Global State of Emergency:
Government’s Role in Curbing
the AIDS Crisis”
Battling Bioterrorism:
Understanding the Scienceand PoliticsX

A Discovery-Based Approachto Understanding Clinical
TrialsGerms In theArts & Humanities

X

X

X

X

X

X

Provided materials

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89NAME ______________DATE ______________CLASS ______________

Using Drugs? You’re In Trouble
Many high schools across the country, including some in North Carolina, have now adopted randomized drug testingfor students participating in extracurricular activities. A 2002 Supreme Court ruling states that this randomized testing is constitutional, as long as the school restricts the testing to those involved in extracurricular activities.

1. Think. Pair. Share.

Ask each student to jot down a few answers to the following questions. After 5-10 minutes, place the students insmall groups to discuss their answers. Each group will then share their thoughts with the class.
• Do you assume that someone who refuses a drug test has something to hide? What other reasons would aperson have for refusing a test?
• Do you think that randomized testing will prevent students from taking drugs?

2. Debate.

Randomly assign half the class to the “pro” side of drug testing, and the other half to the “con” side. Give each side
about 15 minutes to prepare an answer to their assigned question.
• Pro question: What are the benefits of randomized drug testing?
• Con question: What negative impact could testing have?
Allow each group 5-10 minutes to present their case, without interruption. After each team presents, the opposing
side will ask questions. Allow each team 10-15 minutes to respond to the questions.

3. Final Question.

Why was the issue of randomized student drug testing brought before the Supreme Court? Allow students to discuss
for a few minutes. If no one brings up the Bill of Rights, present the students with the text of the Fourth Amendment. Students may discuss or write an essay that addresses whether a school system has “probable cause” to subject
students to drug testing.
The Fourth Amendment to the Constitution
The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches
and seizures, shall not be violated, and no Warrants shall issue, but upon probable cause, supported by Oath oraffirmation, and particularly describing the place to be searched, and the persons or things to be seized.

4. Homework.

Students research the various methods used to conduct drug testing. They may also research the effectiveness ofrandomized testing as a deterrent to drug use.

90

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ANSWERS FOR Using Drugs? You’re In Trouble

KEY

Many high schools across the country, including some in North Carolina, have now adopted randomized drug testingfor students participating in extracurricular activities. A 2002 Supreme Court ruling states that this randomized testing is constitutional, as long as the school restricts the testing to those involved in extracurricular activities.

1. Think. Pair. Share.

Ask each student to jot down a few answers to the following questions. After 5-10 minutes, place the students insmall groups to discuss their answers. Each group will then share their thoughts with the class.
• Do you assume that someone who refuses a drug test has something to hide? What other reasons would aperson have for refusing a test?
o Refusals are often based on the claim that it invades a student’s privacy.
o Students who have never done anything illegal may feel they are being treated unfairly, when they are
targeted for testing.
• Do you think that randomized testing will prevent students from taking drugs?
o Many argue that randomly testing those participating in extracurricular activities targets the very people
who are the least likely to take drugs.
o Two recent studies conducted by the University of Michigan have shown that random drug testing does
not reduce student drug use.

2. Debate.

Randomly assign half the class to the “pro” side of drug testing, and the other half to the “con” side. Give each side
about 15 minutes to prepare an answer to their assigned question.
• Pro question: What are the benefits of randomized drug testing?
o Deterrent to drug use
o Early detection of student drug use allows for more effective intervention• Con question: What negative impact could testing have?
o Fewer students involved in extracurricular activities
o Students become more sneaky about drug use
o Refusal to test, while the right of the student, may lead to false assumptions about the student
o Feeling that the student is “guilty” just because he or she was chosen for a test
Allow each group 5-10 minutes to present their case, without interruption. After each team presents, the opposing
side will ask questions. Allow each team 10-15 minutes to respond to the questions.

3. Final Question.

Why was the issue of randomized student drug testing brought before the Supreme Court? Allow students to discuss
for a few minutes. If no one brings up the Bill of Rights, present the students with the text of the Fourth Amendment. Students may discuss or write an essay that addresses whether a school system has “probable cause” to subject
students to drug testing.
The Fourth Amendment to the Constitution
The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches
and seizures, shall not be violated, and no Warrants shall issue, but upon probable cause, supported by Oath oraffirmation, and particularly describing the place to be searched, and the persons or things to be seized.

4. Homework.

Students research the various methods used to conduct drug testing. They may also research the effectiveness ofrandomized testing as a deterrent to drug use.
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91Global State of Emergency:
Government’s Role in Curbing
the AIDS Crisis
Subjects: World History, Civics and Economics, U.S.
History, American Government
Overview of Lesson Plan: In this lesson, students will
explore the role of the United States in controlling the
AIDS pandemic. Specifically, students will analyze The
President’s Emergency Plan for AIDS Relief (PEPFAR)
and discuss future measures that the U.S. might take inthe global fight against AIDS.
Resources: Handout (attached); copies of The President’s
Emergency Plan for AIDS Relief (found at www.state.gov/
s/gac/rl/or/c11652.htm )Activities/Procedures

1. (15 minutes) Give each student a hand-out (attached)with the following quote from Donna Shalala. Allow
students 10-15 minutes to write down their thoughts on
the listed questions.
In 2000, the Clinton Administration designated HIV/AIDS as a threat to national security. This was the firsttime that a disease has been added to the list of things
that threaten U.S. security. Clinton’s U.S. Secretary of
Health, Donna Shalala, said,
We know that infectious diseases know no borders,
they can affect this country, and in this case it isboth in our economic interest and in our national
security interest to work on these infectious diseases abroad. The high rates of AIDS in Africa are
putting security and stability at risk by disabling
national armies, disrupting economies and killing
off people who might become the next generation of leaders. Basically AIDS is uncoupling the
economic gains in Africa as African countries areforced to shift more resources to their health caresystems from their economic investments . . . .
Eastern Europe has an AIDS problem, Russia has
it, India has it, every country in the world that we
do business with, but more importantly our need
to be politically stable, is suffering from this huge
onslaught of AIDS. And that makes the relationshipeconomically and from the security point of view
relevant to America’s national security.

92

Do you think AIDS is a threat to America’s national
security? This statement was made prior to 9/11. Since
then, bioterrorism has become a very real threat. How
are the effects of bioterrorism (e.g.,
mass numbers of our population
coming down with smallpox)
similar to the effects of an AIDS
pandemic? Why would we be concerned about mass numbers of the
population dying? Is it a threat to our
economy? The global economy?
(Loss of workforce, goods, costof health care.) Are there otherreasons that the U.S. should
get involved in the fightagainst AIDS? (Humanitarian
mission.) List other instancesof U.S. humanitarian assistance in U.S. History. Should the fight be restricted to
the U.S. or should we try to help other countries as well?
(Tie in with global economy and humanitarianism.)
2. (20 minutes) As a class, read pp. 15-16 of PEPFAR,“1. The Global HIV/AIDS Emergency: A Severe andUrgent Crisis.”a. Define “pandemic”:
i. Epidemic over a wide geographic area andaffecting a large proportion of the population
ii. An epidemic is an outbreak of a contagious
disease that spreads rapidly and widely.
b. Discuss the “significant challenges that face allnations, donors, institutions, and individuals.”
Have students offer suggestions for meeting eachof the challenges, including what groups should
be involved.
i. Treatment — antiretroviral drugs (A substance that stops or suppresses the activity ofa retrovirus such as HIV. AZT, ddC, ddI andd4T are examples of antiretroviral drugs.)
Problems include cost and monitoringii. Lack of basic care and support services
iii. Limited infrastructure and human resource
capacity

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iv. Growing orphan population straining community support
v. Inadequate leadershipvi. Stigma of HIVvii. Inefficient use of funds, due to poor
planning and lack of evaluation for the
programs in placec. Discuss why there is no longer a debate over“prevention” versus “treatment.”i. In the beginning of the AIDS outbreak,there was no known treatment. Someargued that money was better spent on
preventing new people from getting thedisease while others said that treating those
who had it could stop its spread. Bothprevention and treatment are necessary toaddress all the challenges.
3. (40 minutes)
a. Divide students into four groups and give eachgroup the relevant section of PEPFAR — leadership (pp. 19-21), prevention (pp. 23-32), treatment (pp. 33-41) and care (43-51).
b. Ask each group to read over their section andcome up with a brief summary and critique ofthat portion of PEPFAR to share with the class.

4. (15 minutes)
a. Wrap-up: Discuss the pandemic as it affects theentire planet. Why is the President’s plan called
an “emergency plan”? Could it be posited that
the U.S. is currently treating the pandemic byfocusing on the 15 countries that are the mostaffected? What is being done to prevent spreadthroughout the world? Specifically, China, India
and Russia are on the brink of a massive AIDS
outbreak. What should they do to prevent this?
How are these countries different socially andeconomically from the ones that the U.S. is helping through PEPFAR? Should the U.S. handle
these countries differently?
b. Homework: Ask students (individually or as agroup project) to research AIDS in China, Russia
or India and come up with a proposal to giveto the leaders of the U.S. and of their chosencountry, to address this impending crisis. A
good introductory article on this subject is “The
Future of AIDS” by Nicholas Eberstadt, found atwww.foreignaffairs.org/20021101faessay9990/
nicholas-eberstadt/the-future-of-aids.html

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93HANDOUT: Government’s Role in Curbing the AIDS CrisiS
In 2000, the Clinton Administration designated HIV/AIDS as a threat to national security. This was the first time thata disease has been added to the list of things that threaten U.S. security. Clinton’s U.S. Secretary of Health, Donna
Shalala, said,
We know that infectious diseases know no borders, that they can affect this country, and in this case it is both inour economic interest and in our national security interest to work on these infectious diseases abroad. The highrates of AIDS in Africa are putting security and stability at risk by disabling national armies, disrupting economies and killing off people who might become the next generation of leaders. Basically AIDS is uncoupling
the economic gains in Africa as African countries are forced to shift more resources to their health care systems
from their economic investments . . . . Eastern Europe has an AIDS problem, Russia has it, India has it, every
country in the world that we do business with, but more importantly our need to be politically stable, is suffering from this huge onslaught of AIDS. And that makes the relationship economically and from the security pointof view relevant to America’s national security.
Do you think AIDS is a threat to America’s national security?

Is it a threat to our economy? The global economy?

Are there other reasons that the U.S. should get involved in the fight against AIDS?

Should the fight be restricted to the U.S. or should we try to help other countries as well?

94

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Battling Bioterrorism:
Understanding the Scienceand Politics
Developed by Susan Hirsch, East Wake High School, and Brian Wood, Enloe High School

OVERVIEW

The fear of an attack of bioterrorism has increased
tremendously since September 11, 2001, and the U.S.
government has budgeted an unprecedented amount ofmoney to be used for research on this topic. In the following activities, students assume the role of researchscientists from different government agencies who
do research and other studies in order to prepare andprevent an attack where chemical or biological agentsare used.
Learning about bioterrorism brings the study of science
into your classroom while following the Social Studies standard course of study. It allows the students toresearch a very timely topic and discover how manyagencies are involved in the defense of our country
against a bioterrorist attack. The four activities described below can be used with a unit on the Legislative
Branch and Congress or while teaching economics andthe government’s budgets.

Objectives• Explore an aspect of the United States’ anti-terrorism
preparations• Learn about the role of scientific research in governmental activities• Discuss the roles of the U.S. Legislative Branch andCongress• Learn about the national budget• Develop public speaking skill

I. Congressional Committee Hearing Simulation on Bioterrorism
Students work in pairs or alone to research a government agency that has been assigned by the U.S. government to research, prepare, and prevent a biological orchemical attack. Let each student/group draw numbers
and whoever draws #1 gets to pick which agency theywant. Continue this practice until all students havechosen. Before the students choose their agency, briefly
explain what each agency is doing.

Government Agencies• Centers for Disease Control and Prevention (CDC)
www.cdc.gov• Food and Drug Administration (FDA)
www.fda.gov• Health and Human Services (HHS)
www.hhs.gov• Homeland Security
www.dhs.gov• Center for Civilian Biodefense Strategies
Johns Hopkins — www.hopkins-biodefense.org• USDAwww.usda.gov• Environmental Protection Agency (EPA)
www.epa.gov• Federal Trade Commission (FTC)
www.ftc.gov• Department of Justicewww.usdoj.gov• Department of Labor (OSHA)
www.osha.gov• U.S. Army Medical Researchwww.usamriid.army.mil/education• FBI
www.fbi.gov• CIA
www.cia.gov• National Institute of Allergy and Infections (NIAID)
www.niaid.nih.gov• Project Bio Shieldwww.whitehouse.gov/bioshield
After students have completed their research, each student or group of students will prepare a 2- to 4-minuteoral presentation, including some type of visual — it
may be poster/s, a PowerPoint, or individual sheetsfor each of the other students. Students make theirpresentations before a congressional committee (classand teacher). The job of each agency (student or groupof students) is to convince the congressional committee

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that their agency deserves be the lead in all research on
bioterrorism. The committee will decide which agency
will take the lead and receive funding for bioterrorism
research.
Each presentation should address the following questions:• What is the main emphasis of the current research
being conducted? (diseases, data reporting, storage,
biodefense, vaccines, preparation, prevention)• What are the plans for future research?
• How much money has been budgeted for your agency
to spend?

II. Bioterrorism “Hype or Threat” Activity
Each of the following possible biological warfare agentsshould be placed on a sign. Make a masking tape lineon the floor. One end of the line represents a low threat
and the other end a high threat based on a scale from 1
to 10. Threat will be defined as likelihood that the agent
would make a practical biological terrorist agent. The
signs should be distributed to students, and the students
will rank each agent in terms of the perceived list. Makea digital camera picture of the rankings.

Possible Biological Warfare Agents

Anthrax
PlagueTularemia
Brucellosis
Q fever
Smallpox
Equine encephalitis viruses
Foot and Mouth Disease
Ebola virus
Hemorrhagic fevers (other than Ebola)
Influenza virus
Staph enterotoxin B
Ricin
Botulism toxins
Trichothecene mycotoxins
Students work in pairs or alone to research specificdiseases or biological agents and develop a five- to tenminute poster or PowerPoint presentation on their assigned biological warfare agent. Let each student/group

draw numbers and whoever draws # 1 gets to pickwhich disease or agent they want to research. Continue
this practice until all students have chosen.
The presentations should include the following information:• History of the bacteria, virus, or toxin• Any use as a biological weapon in the past
• Structure (what does it look like)• Changes such as mutations to make it a more efficientbiological weapon• Mode of transmission including host species• Symptoms and diagnosis• Treatment• Containment options if an outbreak should occur• Social implications including the economic and political impact of an outbreak
A good starting point for research is the Center for
Disease Control website: www.cdc.gov. Emphasize thatstudents should cite their sources.
During the presentation the teacher should give students
participation forms with a section for notes on eachdisease. Students take notes during the presentations
and turn them in for evaluation.
After all of the presentations, the students will repeat
the first exercise to see if their perceptions of the risk ofeach agent have changed and determine if their previous concerns were based on science or media hype.

III. Supplementary Bioterrorism Lesson Plans• Write a handbook on how to clean up a community
after a biological or chemical attack.
• Discuss the Hippocratic Oath and the responsibility ofthe physician to the infected if there was a biologicalattack. If you were in the medical profession, would
you knowingly treat someone who had been infectedwith a contagious disease?

96• Write a grant application to a Biotech company where
you are a researcher wanting to sequence a recently
discovered virus. Give past, present and future usesof this process and convince your supporter that thisresearch is important. (Persuasive letter)• Discuss the economic importance of a biological attack on the U. S. economy. What about on the world
economy?

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• Create a mock drill on how a region would react to asmallpox outbreak.
• Write a report on how the government should prioritize those who should get vaccinated if there is an
outbreak of a contagious disease.

• Go to the Center for Disease Control (CDC) website
and create 10-15 thought-provoking questions aboutbioterrorism and/or plagues that could be used as alesson for the rest of the class.

• Keep a two-week journal as if you were being quarantined because of an outbreak of a contagious disease.

• Research different companies and corporations as
to how they handle their mail since the anthrax andricin-laced letters were mailed in 2001 and 2004
respectively.

• Research the history of a disease such as smallpox andpresent to the class.

• Imagine that you work for the post office. Write a list ofprocedures that should be in place to safely handle mail.

IV. Paideia Seminars: “Effects of Bioterrorism” and The Speckled Monster
Paideia comes from “pediatrician” and “encyclopedia”,
an ancient Greek belief of education that all children
should have a general knowledge base. Paideia is thegeneral learning that should be the possession al all
children.
The Paideia seminar is a formal discussion based on
text, in which the leader of the discussion asks openended questions designed to precipitate spirited andthoughtful dialogue. As a result, the participants are
asked to articulate, justify, and clarify their own ideas
as well as their responses to the ideas of others. The ultimate goal of a seminar is that all participants develop
a more sophisticated understanding of the text throughthoughtful interaction with the ideas of others. Neither
consensus nor closure should signal the end of a seminar; rather continued inquiry and reflection should flow
directly out of the experience.
There are four components of a successful seminar
activity:• Pre-seminar activity — Once the text is given to
the participants, questions or an assignment that
focused on content should be assigned so that
before the seminar, the participants will have readand understood the text.
• Coaching activity — In this component, students
develop in-depth understanding of the topic by
problem solving and application.
• Seminar — The teacher becomes the facilitator and leads the students in a discussion of theassigned texts. The participation of the students
consists of thinking, listening, speaking, referringto the text, and respecting all participants.
• Post-seminar activity — An assignment such asa writing assignment is made to assess and apply
both content and process.

Seminar on “Effects of Bioterrorism”

This seminar activity consists of three readings and canbe used in its entirety or in small parts as class discussions, outside or in-class readings, cooperative learning
activities or as seminars. The readings are “Prologue”
from The Anthrax Letters by Leonard Cole and “The
Horror of Halabja” and “What Leaders and Citizens
Can Do,” from Avoiding Armageddon, with quotes
from former President Mikhail Gorbachev of the Soviet
Union and former President Jimmy Carter of the U. S.
Pre-Seminar Activity: After reading the three selections, complete all activities on this page on your own
paper in ink and answer any questions in complete
sentences.
The Anthrax Letters
1. Write five questions as if you were an investigator that you would ask people who lived on andaround Nassau Street in Princeton, New Jersey.
2. Describe how anthrax was used in the Bible according to the author.
3. Why is anthrax the preferred instrument of terror?
4. List the steps that anthrax spores go throughonce it get in the body.
5. Describe how you would react if you had been
Pat Hallengren on August 10, 2002.
“Horror of Halabja”
Write a one-day journal entry as if you were theIraqi Air Force pilot who flew over Halabja on
March 16, 1988.
“What Leaders Can Do”
Summarize what both Gorbachev and Carter said
was right and wrong with the world. Next, explain
who you agree with the most and why.

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97Coaching Activity: Divide the class into cooperative
learning groups with four students per group and give
each student a copy of the readings “Definition of Bioterrorism” and “History of Biowarfare and Bioterrorism”(www.hs.state.az.us/phs/edc/edrp/es/bioterror.htm) and alarge piece of poster board or construction paper. Divide
the reading into four parts and assign each student in thegroup one section to read. Then have them divide theirposter board in four by drawing a line down and across.
Let them use colored pencils or magic markers and illustrate what they had read on the poster. Once everyone
is finished, have each group present it to the class.
Opening seminar question: What scares you the mostabout bioterrorism?
Core seminar questions:
1. Pat Hallengren’s first thought was of her mailman,
Mario. What would be your first reaction if you had
been in her situation?
2. You are the postal inspector in 2001. What are somerules you would make to keep the mail safe?
3. The person who sent anthrax has not been found as ofyet. If you were an investigator and in the process oftrying to solve the crime, what are some questions thatyou would ask the public to try to arrive at the truth?
4. What punishment would you recommend for the person who committed this crime, if they are found?
5. The secret code for the dropping of nerve gas in Halabja was “Rain, Rain, Rain.” Think of another secretcode that you may have used.
6. Describe how you would react if you were told todrop a chemical gas and kill innocent people or die.
7. Explain what punishment you would inflict on thepilot if you were an American soldier and you arrested him.
8. Analyze one way that what Gorbachev said is different from what Carter said.
Closing Question: The President of the United Statesis in the room. What is one thing you would say to him
about bioterrorism?
Post-Seminar Activity: Write entries in a journal for
14 days as if you had been exposed to a biological orchemical agent but had no symptoms. Each entry must
be dated and be at least one half of a page. Create acover for this journal.

Seminar on The Speckled Monster:A Historical Tale of Battling Smallpox

This book by Jennifer Lee Carrell tells the dramaticstory–both historical and timely–of two parents who

98

dared to fight back against smallpox. This unit concentrates on the introduction (www.speckledmonster.com/
intro.html) to the book, and the chapter “Rosebuds in
Lily Skin” (www.speckledmonster.com/partone.html),
which tells how Lady Mary Wortley Montagu saved herdaughter and helped save the city of London from thedeadliest disease mankind had known. We suggest reading the introduction of the book to the students so thatthey have a frame of reference as what and how thischapter fits into the entire story.
Pre-seminar Activity: Answer all questions in ink on
your own paper and in complete sentences.
1. How did Lady Mary react to John Dryden’squote: Blisters with pride swelled, which
through’s flesh did sprout / Like rosebuds stuck
i’ th’ lily skin about.”
2. What do you think about the above quote?
3. Explain the line “the smallpox had been slashing its way through her friends and family.”4. Why did Lady Mary not take Princess Anne’s
death personally?
5. How did Lady Mary protect her daughter,
Mary?
6. How did King George I react when his son,Prince of Wales, challenged his power in Parliament?
7. What brought the father and son back together?
8. How did the people of London react to theoutbreak of smallpox?
9. What could have prevented the nurse fromcontacting smallpox?
10. What was Lady Mary’s request of Mr. Maitland?
11. What were Mr. Maitland’s demands and why
did they change?
12. What preparations did Lady Mary want toavoid?
13. How did little Mary react to the doctor’s procedure?
14. Who is the hero in this story and why?
Coaching Activity: Divide the class into cooperative
learning groups with four students per group and give
each student a copy of the reading the “Definition of Bioterrorism” and the “History of Biowarfare and Bioterrorism” (www.hs.state.az.us/phs/edc/edrp/es/bioterror.htm)
and a large piece of poster board or construction paper.
Divide the reading into four parts and assign each student
in the group one section to read. Then have them divide
their poster board in four by drawing a line down andacross. Let them use colored pencils or magic markers
and illustrate what they had read on the poster. Once everyone is finished, have each group present it to the class.

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Opening Seminar Question: All vaccinations risk killing or harming some percentage of otherwise healthypeople, in order to protect the majority. What criteria
should be used to decide when to begin vaccinating the
majority of the population? Also, who should decideand who, if anyone is to blame, when things go wrong?
Core Seminar Questions:
1. Explain what made Lady Mary and others like her
willing to risk inoculation in 1721 for themselves
and their family members? Consider the following
arguments:• Emotional and personal• Scientific• Religious• Political• Economic
2. How do the above issues relate to modern concerns
about vaccination?
3. Compare the fears in London of the spread of smallpox to our fear of a bioterrorist attack today. How are
they alike and how are they different?
4. In 1721 the British government tested smallpox
inoculation on prisoners under sentence of death; it
did so with the prisoners’ consent, and in exchange
for pardons. In researching cures and vaccines forvarious diseases, the U. S. government has in the past
run tests on human subjects both with and without
their informed consent. What would have to happen
to make you volunteer to be a part of medical testing
for a cure for a deadly disease?
5. If no one consents to be tested, how should scientists
test the safety of new vaccines and medicines?

6. If you were Lady Mary, how would you have reacted if
your child or you may be exposed to a deadly disease?
7. If you were Princess Caroline, what would you havedone in her situation—pick your spouse or yourchildren?
Closing Seminar Question: Who was the medical heroin our story?
Post-Seminar Activity: Write a one- to two-page
report to be presented to the Department of Homeland
Security on how the government should prioritize those
who should get vaccinated if there is an outbreak of acontagious disease. Include a list of people who should
be charged, if you feel there should be any. Think about
citizens and non-citizens, young and old, healthy andsick, rich and poor, etc.

Online Resources• www.globallink.org.uk/Esc2Saf/Rebwar.htm — Story
and artwork by survivor of chemical attack on the
Kurdish in Halabja, Iraq
• www.pbs.org/wgbh/nova/bioterror/linksandbooks.
html — NOVA online information on bioterrorism• www.pbs.org/newshour/health/bioterrorism/
threat_m.html — Online “News Hour with Jim
Lehrer” about bioterrorism• www.pbs.org/newshour/extra/features/july-dec02/bio.
html — Jim Lehrer’s Web page for students concerning bioterrorism• academic.udayton.edu/health/syllabi/Bioterrorism/
00intro02.htm — On the early biological war on
Native Americans

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99

A Discovery-Based Approachto Understanding Clinical Trials
Subjects: English, Health, Science, Social Studies
Overview: In modern society, the drugs we take and the
medical procedures we undergo are the result of extensive research. Most people have seen the ads for clinical
trials recruiting people with heart disease, high bloodpressure, or some other possible ailment. Yet, many do
not fully understand the procedures involved in clinical research. According to the U.S. National Institute of
Health website, ClinicalTrials.gov, clinical research is
the “fastest and safest way to find treatments that workin people and ways to improve health.”
This lesson plan, designed to be covered in one 90-minute class (or at the end and beginning of two successiveclasses), will help students learn about the make-up ofclinical research and the provisions in place to ensure
the safety of the human participants.
These activities will also be useful in teaching criticalreading and informational writing skills. Social Studies
teachers may wish to expand on the content provided
here by focusing on the history, ethics, and regulationsof clinical trials. General information may be foundat “The history of clinical testing and its regulation”(http://www.roche.com/pages/facets/18/histclinte.htm).
Objectives: Students think critically about the ways inwhich scientific researchers approach health problems,
while also learning to analyze texts and write informational, science-based compositions.

Resources• 3 Handouts (attached): Engagement Activity, FAQ
and Glossary (Understanding Clinical Trials), Exploration Activity (choose either “Strategies for Delivering Anti-HIV Therapy in South Africa” or “Safety ofand Immune Response to a Bird Flu Virus Vaccine in
Healthy Adults”)• Students and teachers may also wish to consult thewebsite ClinicalTrials.gov.

Activities/Procedures

I. Engagement Activity (15 minutes)
a. At the beginning of class, provide each studentwith a copy of the attached “Engagement Activity” handout, which lists four different clinical100

trials. (Alternatively, place the handout on an
overhead projector.)b. Ask the students to look over the handout and jot
down answers to the following questions:i. What is the purpose of each of these trials?
ii. Would you consider participating in one ofthese trials, if you met the requirements?
Why?
iii. Would you do it if you got paid?
iv. What questions would you want to ask theresearchers before you agreed to participate?
v. Would you be interested in the results ofany of these trials? Why?
II. Explore (this activity may also be assigned as individual or group homework) (45 minutes)
a. Divide students into small groups and provide
each group with copies of the attached “Exploration Activity” handout — “Strategies for
Delivering Anti-HIV Therapy in South Africa”
or “Safety of and Immune Response to a Bird
Flu Virus Vaccine in Healthy Adults” and theattached “FAQ and Glossary” handout — “Understanding Clinical Trials” (or direct them to
the ClinicalTrials.gov website).
b. Ask students to complete the “Student Activities”
section of the “Exploration Activity” handout.
III. Explain (15 minutes)
a. Students share the answers to the “Student Activities”
section of the “Exploration Activity” handout with theentire class.

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IV. Elaborate (homework) – choose a or b
a. Students may locate 2 additional clinical trial
descriptions from either the unchealthcare.org
website (clinical trials are listed under “Health &Patient Care”) or the ClinicalTrials.gov website,
and use the descriptions to answer questions 2,
3, and 4 from the “Student Activities” section of
the “Exploration Activity” handout.
b. Using the “Strategies for Delivering Anti-HIV
Therapy in South Africa” or “Safety of and
Immune Response to a Bird Flu Virus Vaccine
in Healthy Adults” as a model, students devise
their own proposed clinical trial. They, of course,
will not conduct this trial but will outline theprotocol, exclusion/inclusion criteria, time-line
and include a description of the proposed trial.
Suggestions for possible trials:
i. The effect of video games on violence inteenagers
ii. The effect of fast food advertising on teenage food purchasesiii. The correlations between wearing sandals
and blistered and calloused feet
V. Evaluatea. Teachers may choose to evaluate students basedon class participation and completion of thehomework assignment(s)ENGAGEMENT ACTIVITY
Think You Might Have Gum Disease?

Lung StudyRESEARCH PATIENTS NEEDEDDo you currently smoke cigarettes?

UNC Center for Inflammatory Disorders-andUNC Center for Oral and Systemic Diseases

Have you quit smoking, but smoked for at least 10 years?

Male and female subjects with periodontal (gum) disease areneeded for a clinical research study. This study will assess theeffect of gum treatments on general health. Eligible subjects
will receive certain treatments at reduced fees or no charge.

The Center of Environmental Medicine at UNC is looking forindividuals for a research study. This study involves 1 visit anda total of 1½ hours of your time.

For information please call or e-mail the
UNC School of Dentistry GO Health Center.

You will be reimbursed for completion of the study.
If you participate, you will have a breathing test andlearn more about your lungs. Participants that areinterested in quitting smoking will be given
information and guidance to help them quit.

Genetic Study ofAnorexia Nervosa in Families

African American Couples
Needed for a Research Study

We are seeking families with at least two members who
have or had anorexia nervosa, and who would be willing toparticipate. Experts from around the world are working tohelp identify the genes that might predispose individuals todevelop anorexia nervosa.

If you have been living with your partner for at least 9 months,
are not taking anti-hypertensive or anti-depressant medications, are between the ages of 18 and 50, and are willing tohave blood samples and blood pressure taken, then you may
qualify for a study about the benefits of partner relationships.

UNC Eating Disorders Program

Receive up to $200 per couple for completion of 2 lab visits.
If interested, please call the UNC
Stress and Health Research Program.
All advertisements on this page were retrieved on April 27, 2005, from unchealthcare.org

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101Understanding Clinical Trials
FREQUENTLY ASKED QUESTIONSWhat is a clinical trial? (from University of Maryland’s brochure “Thinking about Enrolling in a Clinical
Trial”)A clinical trial is an experimental research study that
evaluates the effect of a new drug or medical device
on human beings. Clinical research is a process of
discovery that is intended to improve medical care. Researchers attempt to answer questions such as “Which
medication works better?” or “What is the best way totreat a medical problem?”Who can participate in a clinical trial? (from University of Maryland’s brochure “Thinking about Enrollingin a Clinical Trial”)
All participants in a clinical trial are volunteers who
have agreed to participate in a particular study. Somevolunteers seek out clinical trials, and some are referred
to clinical trial opportunities by their physicians. There
are research opportunities in clinical trials for persons
with specific diseases and conditions and for persons
in generally good health. Volunteers participating ina study are referred to as “subjects” or “participants.”
Volunteers can leave a study at any time for any reason.
What are the benefits and risks of participating in aclinical trial? (from ClinicalTrials.gov)
Benefits• Play an active role in personal health care.
• Gain access to new research treatments before they
are widely available.
• Obtain expert medical care at leading health carefacilities during the trial.
• Help others by contributing to medical research.
Risks• There may be unpleasant, serious or even life-threatening side effects to experimental treatment.
• The experimental treatment may not work for theparticipant.
• The trial may require more time and attention thanstandard treatment, including trips to the study site,
more treatments, hospital stays or complex requirements.
• The participant may be placed in the “placebo” group
How is the safety of the participant protected? (fromClinicalTrials.gov)

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The ethical and legal codes that govern medical practicealso apply to clinical trials. In addition, most clinicalresearch is federally regulated with built in safeguards
to protect the participants. The trial follows a carefully controlled protocol, a study plan which details
what researchers will do in the study. As a clinical trial
progresses, researchers report the results of the trial atscientific meetings, to medical journals, and to various
government agencies. Individual participants’ names
remain secret and are not mentioned in these reports.
Every clinical trial in the U.S. must be approved andmonitored by an Institutional Review Board (IRB)
to make sure the risks are as low as possible and areworth any potential benefits. An IRB is an independent
committee of physicians, statisticians, community
advocates, and others that ensures that a clinical trial is
ethical and the rights of study participants are protected.
What should people consider before participating ina trial? (from ClinicalTrials.gov)
People should know as much as possible about theclinical trial and feel comfortable asking the membersof the health care team questions about it, the care
expected while in a trial, and the cost of the trial. The
following questions might be helpful for the participant
to discuss with the health care team.
• What is the purpose of the study?
• Who is going to be in the study?
• Why do researchers believe the experimental treatment being tested may be effective? Has it been tested
before?
• What kinds of tests and experimental treatments are
involved?
• How do the possible risks, side effects, and benefits inthe study compare with my current treatment?
• How might this trial affect my daily life?
• How long will the trial last?
• Will hospitalization be required?
• Who will pay for the experimental treatment?
• Will I be reimbursed for other expenses?
• What type of long-term follow up care is part of thisstudy?
• How will I know that the experimental treatment isworking?
• Will results of the trials be provided to me?
• Who will be in charge of my care?
• What happens if I’m injured because of the study?

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GLOSSARY
Blind — A clinical trial is “Blind” if participants areunaware on whether they are in the experimental orcontrol arm of the study; also called masked.
Control group — In many clinical trials, one group ofpatients will be given an experimental drug or treatment, while the control group is given either a standard
treatment for the illness or a placebo (See Placebo).
Double-blind study — A clinical trial design in which
neither the participating individuals nor the study staff
knows which participants are receiving the experimental drug and which are receiving a placebo (or anothertherapy). Double-blind trials are thought to produce
objective results, since the expectations of the doctor
and the participant about the experimental drug do notaffect the outcome; also called double-masked study.
Efficacy — The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug
passes efficacy trials if it is effective at the dose tested
and against the illness for which it is prescribed.
Expanded access — Refers to any of the FDA procedures that distribute experimental drugs to participants
who are failing on currently available treatments fortheir condition and also are unable to participate inongoing clinical trials.
Food and Drug Administration (FDA) — The U.S.
Department of Health and Human Services agency
responsible for ensuring the safety and effectivenessof all drugs, biologics, vaccines, and medical devices.
The FDA also works with the blood banking industry tosafeguard the nation’s blood supply.
Inclusion/exclusion Criteria — The medical or social
standards determining whether a person may or may
not be allowed to enter a clinical trial. These criteria
are often based on age, gender, the type and stage of adisease, previous treatment history, and other medical
conditions. Inclusion and exclusion criteria are not used
to reject people personally, but rather to identify appropriate participants and keep them safe.
Informed consent — The process of learning the key
facts about a clinical trial before deciding whether
or not to participate. It is also a continuing process
throughout the study to provide information for participants.
Peer review — Review of a clinical trial by experts
chosen by the study sponsor. These experts review thetrials for scientific merit, participant safety, and ethicalconsiderations.
Phase I trials — Initial studies to determine themetabolism and pharmacologic actions of drugs in humans, the side effects associated with increasing doses,
and to gain early evidence of effectiveness; may include
healthy participants and/or patients.
Phase II trials — Controlled clinical studies conducted
to evaluate the effectiveness of the drug for a particular
indication or indications in patients with the disease orcondition under study and to determine the common
short-term side effects and risks.
Phase III trials — Expanded controlled and uncontrolled trials after preliminary evidence suggesting
effectiveness of the drug has been obtained, and areintended to gather additional information to evaluate theoverall benefit-risk relationship of the drug and provide
and adequate basis for physician labeling.
Phase IV trials — Post-marketing studies to delineate
additional information including the drug’s risks, benefits, and optimal use.
Placebo — An inactive pill, liquid, or powder that has
no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess thetreatment’s effectiveness. In some studies, the participants in the control group will receive a placebo insteadof an active drug or treatment. No sick participant receives a placebo if there is a known beneficial treatment.
Protocol — A study plan on which all clinical trials
are based. The plan is carefully designed to safeguard
the health of the participants as well as answer specificresearch questions. A protocol describes what types ofpeople may participate in the trial; the schedule of tests,
procedures, medications, and dosages; and the length of
the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff
to monitor their health and to determine the safety andeffectiveness of their treatment.
Randomized trial — A study in which participants are
randomly (i.e., by chance) assigned to one of two or
more treatment arms of a clinical trial.
Single-blind study — A study in which one party,
either the investigator or participant, is unaware of what
medication the participant is taking; also called singlemasked study.

Information on this page was retrieved on April 28, 2005, from the National Library of Medicine’s website, ClinicalTrials.gov.
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103Exploration Activity: Strategies for
Delivering Anti-HIV Therapy in South Africa
Sponsored by:

National Institute of Allergy
and Infectious Diseases(NIAID)

Information provided by:

National Institute of Allergy
and Infectious Diseases(NIAID)

Purpose

Providing effective anti-HIV therapy in developing
countries is challenging. This study will evaluate newstrategies for delivering anti-HIV medications to people
in South Africa. These strategies include using speciallytrained nurses to administer therapy (rather than doctors), treating all HIV infected members of a householdat the same time, and having community members
observe patients taking their medications.

Condition

Treatment or Intervention

HIV infections• Behavior: Monitoring by HIV-trained
primary care nurses• Behavior: Community-based directly
observed therapy (DOT)• Drug: stavudine• Drug: lamivudine• Drug: efavirenz• Drug: zidovudine• Drug: didanosine• Drug: lopinavir/ritonavir• Study Type: Interventional• Study Design: Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Efficacy
Study• Official Title: Safeguard the Household: A Studyof HIV Antiretroviral Therapy Treatment Strategies
Appropriate for a Resource Poor Country
Further Study Details:• Expected Total Enrollment: 1050
• Expected completion: December 2011
The benefit of antiretroviral therapy is well establishedbut limited to wealthy nations. A predefined, simple
sequence of treatment regimens focused on extending104

the durability of limited treatment options has the best
potential to be implemented in resource poor countries. South Africa has 15% of the world’s HIV/AIDS
patients and a limited number of physicians to treat
them (l per 1,600 and less than 5 infectious diseases
specialists). HIV patient care in the primary care setting
must therefore be delivered by personnel other thandoctors. Further, treatment strategies should include
entire households to ensure maximum adherence andminimize sharing of drugs.
This study will have two parts. The first part willcompare a first-line antiretroviral therapy regimen
administered and monitored by primary health caresisters (nurses) with the same regimen administered bydoctors. The second part of the study will determine if
community-based directly observed therapy (DOT) is
significantly superior to continued clinic-based treatment
support for patients who have failed first-line therapy, as
measured by cumulative virology failure rate. The project will also evaluate the cost and economic impact of apredetermined schedule of antiretroviral therapy; treatment outcomes in terms of morbidity, opportunistic andendemic infections, and mortality; and factors contributing to treatment failure, including toxicity, resistance,compliance, and treatment interruption.
In Part 1, households will be randomly assigned toreceive first-line antiretroviral therapy under themonitoring and care of either an HIV-trained medical
doctor supported by adherence counselors or an HIVtrained primary health care sister (nurse with training in
diagnosis and treatment prescription). Members of thehousehold who are HIV infected will receive stavudine,
lamivudine, and efavirenz (nevirapine or nelfinavir may
be used for special populations).
Participants who fail first-line antiretroviral therapy
in Part 1 of the study will be entered into Part 2 of thestudy. Participants in Part 2 will receive zidovudine,
didanosine, and lopinavir/ritonavir. Saquinavir/ritonavir will be substituted for lopinavir/ritonavir if theparticipant is receiving treatment for active tuberculosis. Participants will be randomly assigned to havetheir treatment monitored through either a clinic-based
treatment support group or through community-based
directly observed treatment (DOT). For the DOT arm,a community member will observe therapy for at least
one dose a day, five days a week, at the home or workof the participant.

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HIV infected children age 3 months to 16 years wholive in a participating household will also be included in
the study. These children will receive first-line treatment with clinic visits monitored by either the assigned
sister (nurse) or doctor along with their households.
In Part 2, children will be provided with a second-line
treatment regimen with continued daily monitoring ofdoses in the household.
The study will last 5 years.

Eligibility

Ages Eligible for Study: 3 Months and above,
Genders Eligible for Study: Both
Inclusion Criteria for the first person in the household
who enters the study:• HIV infected• Older than 16 years of age• History of a CDC Category C AIDS-defining
illness or a CD4 cell count less than 350 cells/mm3
within 60 days prior to study entry• Have not previously taken anti-HIV medications.
People who have taken anti-HIV medications
for post-exposure prophylaxis or prevention of
mother-to-child transmission may be eligible if theprevious exposure did not exceed 6 weeks of nucleoside reverse transcriptase inhibitors or proteaseinhibitors, or two doses of a non-nucleoside reverse
transcriptase inhibitor.

• Primary caregiver who is willing and able toadminister anti-HIV medications
Exclusion Criteria:• Newly diagnosed AIDS-defining (CDC Classification C) opportunistic infection or condition
requiring acute therapy at the time of enrollment. A
stable patient on therapy for more than 7 days may
be enrolled.
• Use of medications with significant effect on bonemarrow, nervous system, pancreas, or liver within
30 days prior to study entry• Use of cytotoxic medications within 30 days prior
to study entry• Active alcohol or substance abuse• Severe diarrhea (more than 6 stools/day for 7 consecutive days) within 30 days prior to study entry• Acute hepatitis within 30 days prior to study entry• Bilateral peripheral neuropathy of Grade 2 orgreater at the time of screening• Women in the first trimester of pregnancy• Inability to tolerate oral medication• Any clinical condition that, in the opinion of theinvestigator, would make the person unsuitable
for the study or unable to comply with the dosing
requirements
ClinicalTrials.gov processed this record on 2005-05-26

Inclusion Criteria for children less than 16 years old ina household that has been entered in the study:• HIV infected• Live in house with an adult participating in the
study• History of severe CDC Category B or C AIDSdefining illness, with the exception of a single
episode of bacterial sepsis or a single episode of
Zoster; or one CD4% less than 20% (less than 25%
for children 3 to 18 months) obtained within 60
days prior to study entry• Have not previously taken anti-HIV medications.
Children who have taken anti-HIV medications forpost-exposure prophylaxis or prevention of motherto-child transmission may be eligible if the previous exposure did not exceed 6 weeks of nucleosidereverse transcriptase inhibitors or protease inhibitors, or two doses of a non-nucleoside reverse transcriptase inhibitor therapy. Children who received
6 weeks of AZT or a single dose of nevirapine will
be included in the study.
• Consent of parent or legal guardian

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105

STUDENT ACTIVITIES
1. Visit the “Resources” page of ClinicalTrials.gov, and click on “Glossary of Clinical Trial Terms” (or, use thehandout provided by your teacher). Using this glossary, write down definitions for each of the following words:
a. Randomized Trialb. Control Groupc. Efficacy
d. Inclusion/Exclusion Criteria
e. Protocol
2. Answer the following questions:a. What is the purpose of this study?
b. What are the two parts to this study?
c. What are the inclusion criteria for this study?
d. What are the exclusion criteria?
e. Who is sponsoring this trial?
f. What is the trial’s protocol?
g. Why is protocol important?
3. On the front of the “Understanding Clinical Trials” handout, there is a list of questions that people should consider before participating in a clinical trial. Read over this list. (On the website, this list is under the question “Whatshould people consider before participating in a trial?”)a. Using the information provided in the description of the “Strategies for Delivering Anti-HIV Therapy inSouth Africa” clinical trial, answer the list of questions that people should consider before participating in aclinical trial.
b. What questions can you not answer?
c. What could you do to find the answers?
4. What are the possible benefits of conducting this trial, both to the participants and to the general public?

106

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Exploration Activity: Safety of an Immune Response
to a Bird Flu Virus Vaccine (H9N2) in Healthy Adults
Sponsored by:

National Institute of Allergy
and Infectious Diseases(NIAID)

Information provided by:

National Institute of Allergy
and Infectious Diseases(NIAID)

PurposeAvian influenza (AI), or bird flu, has recently becomea major health concern in Asia and other parts of theworld. The purpose of this study is to test the safety ofand immune response to a new AI vaccine in healthy
adults.
Study hypothesis: Influenza A viruses are widely distributed in nature and infect a wide variety of birds andmammals. The direct transmission of avian influenza
viruses from birds to humans has recently become amajor health concern in Asia and other parts of theworld, raising concern of a possible influenza pandemic in humans. This vaccine will evaluate the safety,
infectivity and immunogenicity of Live Influenza A
vaccine H9N2 (6-2) AA ca reassortant (A/chicken/HongKong/G9/97 x A/Ann Arbor/6/60 ca), a cold-adapted,
live attenuated virus vaccine administered intranasallyfor the protection of humans against pandemic influenza
viruses of the H9N2 subtype.

Condition

Treatment or Intervention

Influenzavirus diseases

Vaccine: H9N2 (6-2) AA ca Reassortant(A/chicken/Hong Kong/G9/97 x A/Ann
Arbor/6/60 ca)• Study Type: Interventional• Study Design: Prevention, Non-Randomized,
Open Label, Dose Comparison, Single Group Assignment, Safety Study• Official Title: Phase I Inpatient Study of the
Safety and Immunogenicity of H9N2 (6-2) AA Ca
Reassortant (A/Chicken/Hong Kong/G9/97 x A/
Ann Arbor/6/60 Ca), a Live Attenuated Virus Vaccine Candidate for Prevention of Avian Influenza
H9N2 Infection in the Event of a Pandemic

Further study details as provided by National
Institute of Allergy and Infectious Diseases(NIAID):• Primary Outcomes: Frequency of vaccine-related
reactogenicity events and other adverse effects foreach dose of the H9N2 G9/AA ca reassortant vaccine; immunogenicity and infectivity for each doseof the H9N2 G9/AA ca reassortant vaccine• Expected Total Enrollment: 70
AI viruses in their natural reservoir in waterfowl are
the source from which novel HA and NA subtypes are
introduced into the human population, and have thepotential to initiate an influenza pandemic. This study
will evaluate the safety and immunogenicity of a live,
attenuated, cold-adapted reassortant AI virus vaccine,
H9N2 (6-2) AA ca Reassortant (A/chicken/Hong Kong/
G9/97 x A/Ann Arbor/6/60 ca).
Patient participation in this study will be for at least 60
days, with patients followed for at least 42 days after
vaccination. In this study, participants will be enrolled
sequentially, from highest to lowest dose of vaccine, into
one of three groups. At study entry at Day 0, participants
will be admitted to the hospital in order to familiarize
them with trial procedures. Blood and nasal wash samples will be collected prior to vaccination. On Day 2, participants will have a physical exam and will receive one
dose of vaccine; the vaccine will be administered as nose
drops. Participants will undergo directed physical examinations daily while they are in the hospital. Nasal washes
will also be collected daily from the day of admission
through the day prior to discharge to test for the presenceof vaccine virus. Participants may be discharged from thehospital after 3 consecutive negative viral cultures, but
not before Day 14. Additional blood collection will occur
daily from Day 0 to Day 7 and again on Day 21. Participants will return for follow-up visits 28 to 32 days and 42
to 46 days after receiving the vaccine. Blood and nasal
wash collection will occur at these 2 study visits, andparticipants will also have directed physical exams.
Depending on the immune response to the first dose of
vaccine, some participants may be asked to return tothe hospital one to two months after their first vaccination to receive an additional dose of vaccine at a lower
concentration.

Eligibility

Ages Eligible for Study: 18 Years and above

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107Genders Eligible for Study: Both
Accepts Healthy Volunteers
Criteria
Inclusion Criteria:• Born after 1968
• Good general health• Available for the duration of the trial
Exclusion Criteria:• Clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal
disease• Behavioral, cognitive, or psychiatric disease that,in the opinion of the investigator, affects the abilityof the volunteer to understand and cooperate withthe study• Liver, renal, or hematologic disease• Alcohol or drug abuse within 12 months of study
entry• History of severe allergic reaction or anaphylaxis• Current asthma or reactive airway disease• History of Guillain-Barre syndrome• HIV-1 infected• Hepatitis C virus infected• Positive for hepatitis B surface antigen (HBsAg)

108• Known immunodeficiency syndrome• Use of corticosteroids or immunosuppressive
drugs within 30 days of study entry. Participants
who have used topical corticosteroids are notexcluded.
• Live vaccine within 4 weeks of study entry• Killed vaccine within 2 weeks of study entry• Absence of spleen• Blood products within 6 months of study entry• Current smoker• Have traveled to the Southern Hemisphere orAsia within 30 days prior to study entry• Have traveled on a cruise ship within 30 days
prior to study entry• Work in the poultry industry• Investigational agents within 60 days prior to
study entry, or currently participating in anotherinvestigational vaccine or drug trial• Allergy to eggs or egg products• Purified protein derivative (PPD) positive (positive tuberculosis [TB] test)• Family member with immunodeficiency• Other condition that, in the opinion of the investigator, would affect the participant’s participationin the study• Pregnant or breastfeeding
ClinicalTrials.gov processed this record on 2006-03-09

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STUDENT ACTIVITIES
1. Visit the “Resources” page of ClinicalTrials.gov, and click on “Glossary of Clinical Trial Terms” (or, use thehandout provided by your teacher). Using this glossary, write down definitions for each of the following words
a. Randomized Trialb. Control Groupc. Phase 1 Trials
d. Inclusion/Exclusion Criteria
e. Protocol
2. Answer the following questions:a. What is the purpose of this study?
b. What are the inclusion criteria for this study?
c. What are the exclusion criteria?
d. Who is sponsoring this trial?
e. What is the trial’s protocol?
f. Why is protocol important?
3. On the front of the “Understanding Clinical Trials” handout, there is a list of questions that people should consider before participating in a clinical trial. Read over this list. (On the website, this list is under the question “Whatshould people consider before participating in a trial?”)a. Using the information provided in the description of the “Safety of an Immune Response to a Bird Flu Virus
Vaccine (H9N2) in Healthy Adults” clinical trial, answer the list of questions that people should consider
before participating in a clinical trial.
b. What questions can you not answer?
c. What could you do to find the answers?

4. What are the possible benefits of conducting this trial, both to the participants and to the general public?

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109Germs in the Arts and Humanities
Tuberculosis. TB is featured prominently in music andliterature, especially in the 19th and early 20th centuries. Many of the works listed below are classics thatare regularly taught in English classes. Connecting several topics and activities from Biological Bodyguards
with one of these works will enrich the students’ learning of both science and humanities, providing context
to what may otherwise seem to be abstract knowledge.

Music

La Bohème — Giacomo Puccini
La Traviata — Giuseppe Verdi

AMERICAN Literature

The Bell Jar — Sylvia PlathBritish Literature

Nicholas Nickleby — Charles Dickens

World Literature

An Anonymous Story — Chekhov
The Black Monk — Chekhov
Ivanov - Chekhov
Crime and Punishment — Fiodr Dostoevskii
Demons (The Possessed) — Fiodr Dostoevskii
The Idiot — Fiodr Dostoevskii
Camille (La Dame aux Camilias) — Alexandre Dumas
The Magic Mountain — Thomas Mann
Fathers and Sons — Ivan Turgenev

Syphilis. Literary references to syphilis aren’t always
as direct as those to tuberculosis, but hints do appear inmany texts from previous centuries. A few examples arelisted here.
A Tale of Two Cities — Charles Dickens
A Doll’s House — Henrik Ibsen
Measure for Measure — William Shakespeare
Candide — Voltaire
Latin teachers may want to locate the original Renaissance poem that gave syphilis its name — “Syphilis sive morbus Gallicus” (“Syphilis, or the French
Disease”). It was writtenby the physician Girolamo
Fracastoro (1478-1553),
a native of Verona. The
disease is named after thehero of the poem, a shepherd named Syphilis. At thetime, medical professionals were unsure about theorigins and transmissionof the disease. To quote
the poem (translation by
Girolamo Frascastoro
Nahum Tate, 1686):
Since nature’s then so liable
to change
Why should we think this latecontagion strange?
The offices of nature to define
And to each cause a true
effect assign
Must be a task both hardand doubtful too.
[But] nature always to herself
is true.

110

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