Which is the most serious and most common of the plasma cell dyscrasias? Multiple myeloma Patients progress from the asymptomatic ___ to ___ to the symptomatic disease of multiple myeloma. monoclonal gammopathy of undetermined significance (MGUS); smoldering multiple myeloma (SMM). Patients with multiple myeloma typically have excess plasma cells in ____ a monoclonal immunoglobulin component in the plasma and/or urine, and lytic _____. bone marrow; bone lesions True or False: In multiple myeloma plasma cells infiltrating the bone marrow may be morphologically normal or may show atypical or bizarre cytological features. True In multiple myeloma, the immunoglobulin produced by the malignant clone can be of any type. Which is the most common? IgG (50%) In multiple myeloma, the immunoglobulin produced by the malignant clone can be of any type. After IgG, which 2 are the most common? IgA and IgM (light chains only) Why are an excess of free light chains produced in multiple myeloma? Very the production of heavy and light chains by the malignant plasma cells are not well synchronized In what percent of cases do myeloma cells exclusively produce light chains? 10% Free chains are rapidly excreted in ___. Urine What are free immunoglobulin light chains (κ or λ) excreted in the urine? Jones protein True or False: In multiple myeloma, very rarely, two or more distinct M proteins are produced, or a clinically typical myeloma may produce no secretory product True
In multiple myeloma, compare the level of normal immunoglobulin to the amount of M protein present in the serum The of normal immunoglobulin is often decreased in proportion to the amount of M protein present in the serum The clinical manifestations of multiple myeloma are primarily ___, ___ and ___. Hematologic, skeletal, and immunologic. What percent of patients with multiple myeloma develop deposition disease or amyloidosis 15% What two related disorders have free light chains or fragments of immunoglobulin deposited in the tissues? deposition disease and amyloidosis How do amyloid fibers stained with the dye Congo red appear when viewed under a polarizing microscope? Apple-green birefringence Deposits of light chains in multiple myeloma can be identified in what specimens? With what techniques? Tissue sections; immunofluorescence or immunohistochemical staining with specific antibodies. Criteria for the diagnosis of multiple myeloma include? plasma cells constituting greater than 10 percent of bone marrow cells or a plasmacytoma (a solid tumor mass of plasma cells), plus either serum M protein greater than 3g/dL, urinary M protein, or osteolytic bone lesions. M proteins can be detected in serum or urine by what 2 methods? electrophoresis and immunofixation An important feature supporting the diagnosis of multiple myeloma is the presence of this protein in urine Bence Jones protein Free light chains can be detected in serum or urine by what 2 methods? electrophoresis and immunofixation What disease is a malignant proliferation of IgM-producing lymphocytes and corresponds to lymphoplasmacytoid lymphoma as defined by the WHO? Waldenström’s macroglobulinemia Describe the malignant cells of Waldenström’s macroglobulinemia Malignant cells are more immature than plasma cells and have a microscopic appearance somewhere between that of small lymphocytes and plasma cells. The clinical signs and symptoms of Waldenström’s macroglobulinemia are? Infiltration of the malignant cells into bone marrow, the spleen, and lymph nodes with the overproduction of monoclonal IgM chain
Defects in T-cell-mediated immunity result in recurrent infections with what type of intracellular pathogens? viruses, fungi, and intracellular bacteria What system is part of the innate, antigen-nonspecific immune response and includes neutrophils and mononuclear phagocytic The phagocytic system What system is activated to produce biologically active molecules that enhance inflammation and promote lysis of cells and microorganisms. The complement system What are the mechanisms of the agammaglobulinemias? Genetic defects in B-cell maturation or mutations leading to defective interactions between B and T cells. In evaluating immunoglobulin deficiency states, it is important to remember this varies with age blood levels of immunoglobulins When does IgM reach normal adult levels? 1st year of age When does IgG reach normal adult levels? 5-6 of age True or False: In some normal children, IgA levels do not reach normal adult values until adolescence. True. All infants experience low levels of immunoglobulins at approximately ____ of age, but in some cases, the low levels persist for a longer time. 5-6 months Transient hypogammaglobulinemia of infancy (THI) may result due to what? Low levels of immunoglobulins past 5-6 months of age What is the mechanism of transient hypogammaglobulinemia? Unknown In THI, what type of immunity is normal? Cell-mediated immunity In THI, what Ig is the most affected, dropping at 2 SDs below the age-adjusted mean? IgG THI patients have normal numbers of circulating CD19 positive unlike what agammaglobulinemia? Bruton’s agammaglobulinemia First described in 1952, this agammaglobulinemia is X chromosome–linked, and so affects males almost exclusively. Bruton’s agammaglobulinemia
What group of disorders is common variable immunodeficiency (CVI)? It under the heterogeneous group of disorders. This disorder is considered a disorder; although it still remains the most common primary immune deficiency with a severe clinical syndrome. The common variable immunodeficiency syndrome. How is the CVI disorder acquired? Congenital or acquired, familial or sporadic. Is it seen more in men or women? It occurs with equal frequency in men and women. What is CVI characterized by? Hypogammaglobulinemia What can it lead to? Recurrent bacterial infections, particularly sinusitis and pneumonia. What percentage of CVI patients develop herpes zoster (shingles)? 20 percent, which is a much higher incidence than in immunologically normal young adults. What immunoglobulin is usually deficient? Both IgA and IgG, but selective IgG deficiency may occur. What type of reoccurring infections are typically seen when diagnosing patients that demonstrate a low serum IgG level? They tend to have recurrent bacterial infections. In contrast to X-linked agammaglobulinemia, most patients with CVI have normal numbers what type of cell? Mature B cells How many subclasses of IgG are in humans? Four Out of the IgG, what percentage of the IgG1 is normally present? About 70 percent Out of the IgG, what percentage of the IgG2 is normally present? About 20 percent Out of the IgG, what percentage of the IgG3 is normally present? About 6 percent Out of the IgG, what percentage of the IgG4 is normally present? 4 percent In patients with recurrent infections, what testing should be performed if the total IgG levels are normal but the clinical picture suggests immunoglobulin deficiency. levels of the different subclasses should be measured. If the total IgG level was normal could there still be a deficiency in one of the subclasses? Yes, a deficiency of a single IgG subclass may not result in a IgG level below the normal range. Increased bacterial infections may result from what? IgG subclass deficiencies.
Defects in cell-mediated immunity can result from abnormalities in what stages? Many different stages of T-Cell development What types of defects can result in severe combined immunodeficiency (SCID)? Molecular defects Besides primary defects in immunity what other effects can happen? Can also have secondary effects on humoral immunity. In general, defects in cellular immunity are more difficult to manage than what other defects? Defects in humoral immunity Patients with severe defects in immunity may develop what disease? They can develop graft-versus-host (GvH) disease. This happens when the donor lymphocytes are allowed to survive, proliferate, and attack the recipient’s tissue as foreign. A severe defect in the T-cell system. When can GvH disease occur? GvH disease can in any individual with a severe defect in cell-mediated immunity (e.g., in bone marrow transplant recipients) and can be fatal. GvH disease also occurs in patients who have received this type of transplant. A bone marrow transplant. This anomaly affects thymic development. DiGeorge anomaly is a developmental abnormality of the third and fourth pharyngeal pouches that affects thymic development. All organs derived from these structures can be affected. Embryonic structures DiGeorge anomaly associated abnormalities include what? Mental retardation, absence of ossification of the hyoid bone, cardiac anomalies, abnormal facial development, and thymic hypoplasia. The severity and extent of the developmental defect can be quite variable in this disease. DiGeorge anomaly The immunodeficiency associated DiGeorge anomaly is a quantitative defect in what type of cells? Thymocytes Insufficient types of these are made, but those that are present are functionally normal. Mature T cells One immunodeficiency for which a specific enzymatic basis has been defined is what? Purine nucleoside phosphorylase (PNP) deficiency, a rare autosomal recessive trait. The condition presents in what age group and has recurrent or chronic pulmonary The condition presents in infancy
This is a group of disorders inherited as either an X-linked or autosomal recessive gene that affects neutrophil microbicidal function. Chronic granulomatous disease (CGD) This disease accounts for 70 percent of the cases, and it tends to be more severe. X-linked disease Symptoms of CGD include recurrent what? Suppurative infections, pneumonia, osteomyelitis, draining adenopathy, liver abscesses, dermatitis, and hypergammaglobulinemia. CGD is the most common and best characterized of this type of abnormalities? The neutrophil abnormalities There are three different autosomal recessive genes involved, and all of these affect subunits of what? Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. What normally leads to the production of reactive oxygen molecules, such as hydrogen peroxide (H2O2), by NADPH oxidase on the plasma membrane? Normally, neutrophil stimulation These granules fuse with, and release their contents into, the forming phagosome, as organisms are phagocytized. Neutrophil granules What is used by the granule enzyme myeloperoxidase to generate the potent microbicidal hypochlorous acid. Hydrogen peroxide The process of generating partially reduced forms of oxygen by stimulated neutrophils was first detected as what? An increase in oxygen consumption. This response was originally termed the neutrophil “respiratory burst”; a more correct term is called? “oxidative burst.” In CGD, neutrophils are unable to do what? undergo the oxidative burst CGD was historically diagnosed by measuring the ability of a patient’s neutrophils to reduce what dye? The dye nitro-blue tetrazolium (NBT) More recently, this has become available. a flow cytometric assay In this assay, what are neutrophils labeled with? dihydrorhodamine (DHR) DHR will do what when it is reduced. fluoresce The neutrophils are then activated using this, which is mitogenic for neutrophils. Phorbol myristate acetate (PMA)
The resultant oxidative burst will reduce the DHR, resulting in what? Fluorescence that may be quantified by flow cytometry. Neutrophils from CGD patients will be unable to undergo this reaction and will show less fluorescence than normal neutrophils. oxidative burst This deficiency leads to an inability to generate enough NADPH to supply reducing equivalents to the NADPH oxidase system. Neutrophil glucose-6-phosphate dehydrogenase deficiency. This deficiency leads to a defect in hydrogen peroxide production and a clinical picture similar to that of what other disease? CGD (Chronic granulomatous disease) Even if this is normal, neutrophils cannot perform their functions properly if they fail to leave the vasculature and migrate to a site of incipient infection. microbicidal activity These play important roles in microbicidal activity. Adhesion receptors on leukocytes and their on endothelial cells and extracellular matrix What causes a protein deficiency in a component of adhesion receptors on neutrophils, monocytes, and T cells? LAD: Leukocyte adhesion deficiency What proteins does LAD affect in neutrophils, monocytes, and T Neutrophils: CD18 Monocytes: CD11b or CD11c T cells: CD11a How are the leukocytes affected with LAD? Abnormal adhesion, motility, aggregation, chemotaxis, and endocytosis What is the clinical manifestation with LAD? Delayed wound healing, chronic skin infections, intestinal and respiratory tract infections, and periodontitis How can a CD18 defect be diagnosed? By detecting a decreased amount of CD11/18 antigen with flow cytometry. What can lead to deficiencies in each of the major complement components and lead to various clinical sequelae? LAD: Leukocyte adhesion deficiency Deficiencies in early complement components (C1q, C4 and C2) are associated with what type of syndrome? Lupus-like syndrome Which is the most common complement component deficiency? A deficiency in C2 What differentiates C3 deficiency from other lupus-like clinical presentation? And increased likeliness of recurrent encapsulated organism infection.
What binds to cell surface molecules on the lymphocytes as induction agents and to treat severe rejection episodes? Monoclonal antibodies. OKT3 is a monoclonal antibody that binds to the on human lymphocytes. CD3 receptor True or False. The binding of OKT3 to the CD3 T-cells surface has one outcome. False. What may render the affected T cells nonfunctional? Binding may modulate CD3 from the cell surface. How do higher doses of antibody deplete T cells from circulation? With complement-mediated or opsonization for removal by phagocytic cells. What problem is with monoclonal antibody preparations administered to patient? The development of anti-mouse antibodies by the patient. When are two polyclonal anti-T-cell antibody preparations used? To treat severe rejection. Thymoglobulin is a an anti-thymocyte antibody prepared in . Rabbit. ATGAM is a polyclonal antiserum prepared from immunization of . Horses. Name the two immunosuppressive agents that are potent enough to deplete lymphocytes from the circulation. Thymoglobulin and ATGAM. What activity can the development of these anti-mouse antibodies interfere with? The activity of the monoclonal antibody. What is the drawback associated with administration of polyclonal antibody preparations? The development of serum sickness due to antibody responses to the foreign immunoglobulin. What are the two main activities carried out by histocompatibility laboratories in support of transplantation? HLA typing and HLA antibody screening/identification. What is HLA typing? The phenotypic or genotypic definition of the HLA antigens or genes in a transplant candidate or donor. For clinical HLA testing, of the classical transplant antigens or genes are determined (HLA-A, B, Cw, DR, DQ). Phenotypes or genotypes. What information is used to find the most suitable donor–recipient combination from an immunologic standpoint? Histocomplatibility. True or False. False.
What is the alternative way to detect binding of antibody? By flow cytometry using an FITC-labeled anti- IgG reagent. As for antibody screening and identification, what is the most sensitive method for detecting donor-specific antibody? The flow cytometric crossmatch How to define tumor immunology? It is a study of the antigens associated with tumors, the immune response to tumors, the tumor’s effect on the host’s immune status, and the use of the immune system to help eradicate the tumor How is understood tumor immunology? It is best understood with the background on differences between tumor cells and normal cells. Why normal cell growth and division are regulated processes? It is designed to rapidly produce new cells when necessary, inhibit cell division when sufficient cells are present, and limit cell lifespan (programmed cell death, or apoptosis). How do we name the regulatory genes that promote cell division? Protooncogenes What protooncogenes can cause? They uninhibit cell division if their expression is altered or if they are mutated into oncogenes. What can cause tumors? Mutations or malfunctions in tumor suppressor genes that remove growth-inhibitory signals. What cells form tumors? Cells that possess many of the attributes of the normal cells from which they arose but have accelerated or dysregulated growth. If a tumor does not invade surrounding tissue and normal body function is largely preserved, it is said to be? Benign tumor. What tumors invade surrounding tissues and greatly disrupt normal body function? Malignant tumors. What is the stage when the malignant cells travel through the body, causing new foci of malignancy until body function is so disrupted that death occurs? Metastasis. How malignant cells typically differ visually from normal cells? They are metabolically more active to support their growth, and express different genes or different levels of gene products as compared to normal cells. What have aberrant morphology and express different surface antigens either in type or amount? Leukemic cells. Is the conversion of a normal cell to a malignant cell is typically a process, or an event? It is a process.
What are needed to demonstrate completely success vaccines? of DC delivery Why are immunization protocols important? Protocols are important adjunct to traditional therapies What is the first step of traditional tumor therapy? Tumors will first be de-bulked In tumor therapy what will eradicate immune system after tumors will be Residual tumor and micro metastases What is the reason of active and increased optimism in recent years? The increased understanding of tumor immunology The specific immune response to bacterial infections includes formation of what? antibodies Antibodies in a response to bacterial infection are produced to what? to exotoxins or other secreted bacterial products Antibody formation is the main defense against what bacteria? extracellular bacteria What is helpful in attacking intracellular bacteria? cell-mediated immunity Why Bacteria have developed several ways? to inhibit the immune response Why Bacteria have developed several ways? make it more difficult for the immune response to occur What is one of the mechanism of bacterial development to inhibit immune response? avoiding antibody What is one of the mechanism of bacterial development to inhibit immune response? blocking phagocytosis What is one of the mechanism of bacterial development to inhibit immune response? inactivating the complement cascade How does the mechanism of avoiding the effects of antibody occur? through altering bacterial antigens (epitopes) The mechanism of avoiding the effects of antibody through altering bacterial antigens (epitopes) as a result of what? genetic mutations How some bacteria can avoid effect of antibodies? By down-regulation of MHC molecules How some bacteria can effect of antibodies? produce proteases that degrade IgA What is a target of most of the evasion mechanisms of bacteria? the process of phagocytosis What are the stages of bacterial defense in the process of phagocytosis? chemotaxis, adhesion, and digestion
Antibodies are produced to what exoantigens or exotoxins? nicotinamide adenine dinucleotidase (NADase) Antibodies are produced to what exoantigens or exotoxins? Streptokinase What diagnosis must be used to identify rheumatic and glomerulonephritis? Serological Why do serological diagnosis used to identify rheumatic fever and glomerulonephritis? Because the organism is unlikely to be present in the pharynx or on the skin at the time symptoms appear What do A streptococci elaborate? more than 20 exotoxins The antibody response to one or more of exotoxins of A streptococci is used as documentation of nonsuppurative disease The antibody response to streptococcal products is variable due to what factor? age of onset The antibody response to streptococcal products is variable due to what factor? site of infection The antibody response to streptococcal products is variable due to what factor? timeliness of antibiotic treatment What is one of the most diagnostically important antibody? antistreptolysin O (ASO) What is one of the most diagnostically important antibody? anti-DNase B What is one of the most diagnostically important antibody? anti-NADase What is one of the most diagnostically important antibody? antihyaluronidase Assays for detection of antibodies can be performed individually or by using what kit? Streptozyme kit Streptozyme kit is useful because detects antibodies to all streptococcal products The onset of clinical symptoms of rheumatic fever or glomerulonephritis typically coincides with what? with the peak of antibody response What is considered significant if acute and convalescent phase sera are tested in parallel? fourfold rise in titer Why using of at least two tests for antibodies to different exotoxins is recommended? because production of detectable ASO does not occur in all patients The most commonly used are antistreptolysin O (ASO) and anti-DNase B Antihyaluronidase tests are available for research or reference laboratories Presence of what factor does indicate recent streptococcal infection in patients suspected of having acute rheumatic antibodies to streptolysin O