bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory Mediators
Authors: Alvine Travis D , Knopick Peter L , Nilles Matthew L , Bradley David S 
Published: September 2015

AbstractCytokines and chemokines are soluble inflammatory mediators that are naturally produced during an inflammatory response. The type of immune response (pro‐ or anti‐inflammatory, cell mediated or humoral) elicited by these molecules largely depends on the initial cytokines released in response to bodily injury or pathogen invasion. The characteristic signs of inflammation: redness, swelling, heat and pain are the result of coordinated, intricate signalling responses by these soluble mediators that primarily facilitate cellular infiltration to the site of infection. The nature of the immune response is further complicated by the fact that several cytokines can promote both pro‐ and anti‐inflammatory responses. Although cytokines and chemokines are often effective at resolving inflammation, aberrant cytokine and chemokine signalling have been shown to contribute to many autoimmune diseases.Key ConceptsFine‐tuned immune signalling is critical for resolution of potentially harmful stimuli.Inflammatory mediators are the molecules responsible for immunological homeostasis.Cytokines and chemokines link the innate and adaptive immune systems.Inflammatory mediators regulate physiological processes distinct from the immune system.Cytokines and chemokines are powerful signalling proteins.Arachidoic acid is synthesised into prostaglandins and leukotrienes.Activation of the complement system yields anaphylatoxin production.
Hepatitis
E
Virus
Authors: Lhomme Sebastien , Abravanel Florence , Chapuy‐Regaud Sabine , Dubois Martine , Mansuy Jean‐Michel , Peron Jean‐Marie , Alric Laurent , Rostaing Lionel , Kamar Nassim , Izopet Jacques 
Published: September 2015

Abstract

The hepatitis E virus (HEV) infection is a worldwide disease. HEV is usually responsible of an acute self‐limiting infection, but pregnant women and patients with preexisting liver disease can suffer from severe forms. HEV infections can lead to chronic hepatitis and cirrhosis in immunocompromised patients. Extrahepatic manifestations can also occur. In developing countries, HEV is transmitted via contaminated water. In developed countries, transmission is zoonotic due to consumption of uncooked or undercooked infected meat and direct contact with infected animals. Transfusion‐transmitted HEV infections were also described. HEV infections are diagnosed by detecting anti‐HEV antibodies in the serum. In immunocompromised patients, detecting HEV RNA in the blood or faeces is needed. A 3‐month course of ribavirin is effective for treating chronic infection: a sustained virologic response occurs in 78% of patients. Vaccine has been recently licensed for use in China and provides protection against hepatitis E for up to 4.5 years.

Key Concepts

The hepatitis E virus infection is a worldwide disease.

Animal reservoir is responsible for autochthonous HEV infection in developed countries.

Chronic infections are possible in immunocompromised patients.

Treatment of choice for chronic HEV infections is a 3‐month course of ribavirin.

Vaccine afforded a sustained protection.
Picornaviruses
Authors: Rowlands David J 
Published: September 2015

Abstract

The name picornavirus is derived from
pico
for small and ribonucleic acid (RNA), denoting the chemical nature of the genome. Virions are nonenveloped icosahedral particles approximately 30 nm in diameter. The capsid is constructed from 60 copies of each of four structural proteins, which account for 70% of the particle mass and enclose the single‐strand genome of 7500–8500 nucleotides. The positive‐strand genome acts directly as a messenger RNA to template a single polyprotein product. This is subsequently processed by virally encoded proteases into mature active proteins. Several intermediate products have distinct functions to the final fully processed proteins. Replication of the genome is initiated by an uridylated peptide and proceeds via a negative‐strand intermediate template. Picornaviruses are among the smallest pathogens of vertebrates and are responsible for many important diseases in humans and animals.

Key Concepts

There are effective vaccines against polio, hepatitis A and foot‐and‐mouth disease viruses. In addition, movement control and slaughter is used to control foot‐and‐mouth disease. There are no licensed drugs for picornavirus infections.

Genome sequence comparisons have replaced biological and biophysical comparisons as the bases for classification within the family.

Picornavirus particles comprise 60 copies each of four structural proteins, which form a quasi‐T1 icosohedral capsid encasing the single‐strand RNA genome.

The picornavirus RNA genome functions as a messenger RNA to template the synthesis of a single polyprotein, which is posttranslationally processed by viral proteases.

Picornaviruses bind to cell‐specific surface receptors, and this interaction is an important factor in determining host and tissue specificity of each virus.

Picornaviruses cannot gain entry to cells by membrane fusion, as is the case for enveloped viruses, and require special mechanisms to breach cellular membranes and safely deliver the genome into the host cell.

Genome replication occurs in association with virus‐modified cellular membranes. Viral RNA templates complementary negative‐strand molecules, which in turn template multiple positive‐strand copies. The synthesis of all RNA molecules is initiated by an uridylated peptide primer.

The mechanisms of transmission of infection play key roles in the epidemiology of picornavirus infections.

Picornaviruses are responsible for a wide range of clinical diseases resulting from multiple factors such as receptor specificity, tissue‐specific susceptibility, virulence and the mechanisms of transmission.
Neutrophils
Authors: Borregaard Niels 
Published: September 2015

AbstractProduction of neutrophils occupies almost two third of the activity in bone marrow. Production and release are governed by the level of granulocyte‐colony‐stimulating factor and by chemokines that provide either retention signals or release signals. Circulating neutrophils are directed to sites of infection by endothelial cells in postcapillary venules at sites of infection. The endothelial cells capture by‐passing neutrophils and guide the neutrophils across the endothelial cell layer. The neutrophils then migrate towards the invading microbes guided by signals produced by the microbes and sensed by the neutophils. Killing of microbes takes place largely in a phagocytic vacuole created by uptake of the microbes and fusion of granules with the membrane surrounding the microbes taken up. Here, killing is effectuated by granule proteins and by bactericidal reactive oxygen metabolites created by the neutrophil respiratory burst activity. Thereafter, the neutrophil may undergo apoptosis and become phagocytosed by macrophages or undergo NETosis with extrusion of nets of DNA that may limit bacterial spread.Key ConceptsProduction of neutrophils is quantitatively the most important activity in the bone marrow.Endothelial cells that are activated by local infection/inflammation capture by‐passing neutrophils and guide them to the site of infection.Bacteria are taken up by neutrophils into a phagocytic vacuole created by the plasma membrane which wraps around the ingested microbes and fuses with granules.Killing is effectuated by a combination of exposure of microorganisms to highly reactive oxygen species generated by neutrophils in the phagocytic vacuole and by bactericidal proteins stored in granules and liberated to the phagocytic vacuole.Death of neutrophils by apoptosis regulates the production of neutrophils by a feedback loop that tunes production of G‐CSF according to the rate of apoptosis.Death by NETosis involves extrusion of DNA associated with antimicrobial peptides. This may provide defence against spread of microorganisms.
Antigen Processing
Authors: Gardiner Gail J , Deffit Sarah N , Blum Janice S 
Published: September 2015

AbstractAntigen presentation is an important mechanism by which the immune system recognises infection and maintains self‐tolerance. In order to effectively present antigens to T lymphocytes, intracellular enzymes degrade antigenic macromolecules into short fragments, which then bind major histocompatibility complex class I and class II molecules, or alternatively nonpolymorphic major histocompatibility complex class Ib molecules. This process of fragmentation is known as antigen processing and is shaped by the specificity of the enzymes involved as well as the intracellular compartments where processing takes place. Key players in antigen processing include cytoplasmic enzymes such as the proteasome and calpain, as well as cysteine cathepsins, aspartyl proteases, NADPH oxidase and GILT, which all reside in acidic vacuolar compartments. The trafficking of antigens to different intracellular compartments influences the sequence of processing and the selection of antigenic epitopes, which are displayed on the cell surface to promote immune activation or tolerance.Key ConceptsTrafficking of antigens into proper compartments affects the degradation and availability of epitopes for both MHC‐I and MHC‐II presentation.Proteasome activity affects MHC‐I peptide generation and endogenous cytoplasmic peptide generation for MHC‐II.ROS production by NADPH oxidase can affect MHC‐I cross‐presentation and MHC‐II presentation.Cathepsin activity, which is regulated by endosomal pH, generates peptides for MHC‐I cross‐presentation and MHC‐II presentation.The reduction of disulphide bonds by GILT affects availability of epitopes for MHC‐II presentation.While homologous to MHC‐I, nonclassical MHC‐Ib acquire antigens processed in acidic compartments much like MHC‐II.
Immunodeficiency, Primary: Affecting the Adaptive Immune System
Authors: Vihinen Mauno 
Published: September 2015

Abstract

Primary immunodeficiency (PID) is an intrinsic defect of the immune system. Patients with PID have increased susceptibility to recurrent and persistent infections, and they may also have autoimmune and cancer‐related symptoms. PIDs are mainly rare hereditary disorders of the immune system which often have serious consequences. Infections are the hallmarks of PIDs. Clinical descriptions have already been made for about 250 PIDs, for which approximately 200 genetic aetiologies have been described. There are several different mechanisms behind PIDs. Some PIDs affect T‐ or B‐cell functions, and when both cell types are affected, it leads to severe combined immunodeficiencies (SCIDs). Other PIDs affect major histocompatibility complex, antibody production, lymphocyte apoptosis, phagocytosis, complement cascade or the innate immune system. PIDs are a constantly growing group of mainly rare diseases that help to understand how the complex immune system is composed, acting and regulated.

Key Concepts

Adaptive immunity is a specific and long‐lasting response of lymphocytes to antigens.

Combined immunodeficiency affects both B and T cells.

Lymphocytes are white blood cells including B and T cells.

Signal transduction is a process by which a cell converts one kind of signal or stimulus into another. In a signalling cascade, an extracellular signal interacts with a cell surface receptor, which leads to a change in the level of a second messenger and ultimately a change in the cells functioning.
Typing for Transplantation Antigens and Their Genes
Authors: Briggs David , Jobson Shirley 
Published: September 2015

Abstract

Safe and effective clinical transplantation requires human leucocyte antigen (
HLA
) typing of donors and recipients. Various immune diseases are associated with particular
HLA
types and
HLA
typing can be of diagnostic value. Finally,
HLA
typing is used increasingly in peptide vaccine design for cancer treatment.
HLA
typing is now carried out at the
DNA
level, which allows testing ranging from high resolution (i.e.
DNA
sequencing) to low resolution (which defines broadly related allele groups). The clinical application dictates the required resolution and therefore the method. Successful haematopoietic stem cell transplantation usually depends on exact
HLA
matching and therefore the higher resolution of testing, while for solid organ transplantation, lower resolution testing is generally sufficient. Current
DNA
testing methods rely on a polymerase chain reaction stage to either generate target
DNA
for analysis or generate sufficient specific
DNA
to detect directly. A systematic nomenclature for
HLA
has been developed and refined to account for the different methods of testing and the extreme genetic variability of the
HLA
system. The latest approaches to
HLA
typing use next generation sequencing (
NGS
) and, although not yet in widespread use in H&I laboratories, these may well provide definitive HLA typing for all applications in the near future.

Key Concepts

There are two classes of HLA with multiple members of each class (A, B and C for Class I and DR, DQ and DP for Class II).

HLA proteins are determined by the most polymorphic genes in humans – over 12 000 known alleles that determine nearly 9000 genetically different proteins (allotypes).

An HLA allele is defined by its entire DNA sequence. There is much sharing of certain polymorphic sequences between different alleles.

HLA nomenclature is complex but systematic.

Serological typing, the first approach used for HLA, discriminates alleles poorly because of the lack of a full range of antibodies.

Rapid HLA typing is currently best achieved using allele‐specific PCR, whereby DNA primers are used to discriminate between selected sequences in different alleles.

Typing using DNA probes to discriminate between sequences in different alleles is cost‐effective for large‐scale clinical testing.

The highest resolution of HLA typing requires genomic DNA sequencing.

Low‐resolution typing can give ambiguous results in heterozygotes (i.e. various allele combinations).
Complement: Measurement
Authors: Morgan Bryan Paul 
Published: September 2015

Abstract

Complement comprises more than 30 proteins present in plasma, other biological fluids and on cell surfaces that collaborate in the host defence against infection. The components of the pathway interact in a sequential manner to efficiently label pathogens; self‐cells are protected by plasma and membrane regulators, and cells bind and respond to products of activation through specific membrane receptors. Measurement of complement components, activation products and activity can be clinically useful in several situations: first, where there is a suspicion of a complement deficiency; second, where complement activation is suspected in a disease and third, to monitor effect of a therapeutic intervention on complement activation or activity. This article describes methods for measuring levels of complement proteins, activation products and complement activity in biological fluids and discusses recent developments in the field. In particular, the interindividual variability in complement activity is described and the relevance of this inherited ‘complotype’ on disease susceptibility discussed. The advent of effective anticomplement drugs, already in clinical use in several disease areas, opens a new area in which effective measurement of complement will be an essential requirement.

Key Concepts

Correct sample collection and storage is essential for effective measurement of complement.

Functional assays of complement haemolytic activity provide the best screen for suspected deficiencies.

Immunochemical measurement of circulating complement components and activation fragments can be performed by commercial assays, nephelometric, turbidimetric or ELISA.

Pathway‐specific and individual component‐specific functional assays of complement activity are required to detect deficiencies that do not affect immunochemical levels.

Functional complement assays are highly dependent on the choice of target cell and buffer composition, particularly the presence of calcium and magnesium ions.

Modern structural analyses and biosensor assays allow an in‐depth analysis of the affinity and kinetics of complement component interactions that reveals the impact of mutations and polymorphisms.

National and international quality control of complement assays has been lacking in the past and is required for meaningful interlaboratory comparisons.
Eosinophilia and the Hypereosinophilic Syndrome
Authors: Hsieh Fred H 
Published: September 2015

Abstract

The eosinophilic granulocyte is involved in the pathogenesis of diverse inflammatory processes, some of which may be beneficial to the host, such as in host defence against parasitic infection, and others are implicated in disease. In addition to being associated with allergic and atopic disease, eosinophilia can be seen in multiorgan system disorders, such as with rheumatologic and hematologic diseases, and can also be associated with single‐organ system disease involving the lungs, the heart, skin and soft tissues, and the gastrointestinal tract. Hypereosinophilia is characterised by the prolonged elevation of the peripheral blood eosinophil count, and the hypereosinophilic syndrome (HES) refers to a group of disorders marked by hypereosinophilia with multisystem target organ damage. The molecular pathogenesis of selected clonal and secondary HESs has been identified, and recognition of specific molecular defects can help to guide specific treatment approaches.

Key Concepts

The eosinophil is a myeloid lineage granulocyte derived from the hematopoietic stem cell.

Interleukin‐5 is the key cytokine involved with eosinophil lineage commitment, development, expansion, homing and activation.

Eosinophils produce a diverse array of mediators but there are at least four specific mediators unique to eosinophils – eosinophil cationic protein, eosinophil‐derived neurotoxin, eosinophil peroxidase and major basic protein.

A vast array of human diseases is associated with eosinophilia, including single‐organ system involvement and multisystem involvement.

The hypereosinophilic syndrome (HES) is defined by having a peripheral blood eosinophilia >1500 cell/μL for at least 1 month, with evidence of eosinophil‐dependent target organ damage, and all other aetiologies of eosinophilia excluded.

The myeloproliferative variant HES is characterised by abnormal PDGFRA signalling and is markedly sensitive to tyrosine kinase inhibitors targeting PDGFRA.

The lymphocytic variant HES is a reactive eosinophilia driven by clonal, nonmalignant T cells with abnormal immunophenotype secreting high concentrations of eosinophilpoietins such as IL‐5.
Atopy and Asthma
Authors: Yates Anne B , deShazo Richard D 
Published: September 2015

Abstract

Atopy is the genetic propensity to develop an immunoglobulin E antibody response to common allergens. The most common clinical manifestations of atopy are allergic rhinitis, asthma and atopic dermatitis. Asthma is a complex disorder of the airways, involving airway hyperresponsiveness, airflow obstruction that is at least partially reversible, and inflammation of the airways. Although atopy has been identified as the strongest predisposing factor for the development of asthma, not all asthma is allergic in nature. The overall prevalence of asthma has been increasing worldwide for the last few decades, and continues to increase globally. Guidelines for the evaluation and treatment of asthma were developed in the early 1990s, and are revised periodically as research into effectiveness of available medications emerges, and development of new therapies arise.

Key Concepts

Immunoglobulin E (IgE), produced by atopic individuals, plays a key role in allergic disorders, with atopic asthma being a prime example of IgE‐mediated inflammation.

Asthma is a common but complex disorder of the airways, involving variable and recurrent symptoms, airway obstruction, inflammation and bronchial hyperresponsiveness.

Symptoms of asthma include coughing, wheezing, shortness of breath and feelings of chest tightness or pain with breathing.

Numerous comorbidities may complicate and exacerbate asthma.

Onset of asthma usually begins early in life, although adult‐onset of asthma may occur.

Genetic predisposition and environmental factors play a role in the development of asthma.

The diagnosis of asthma depends on the appropriate historical symptoms, physical examination, objective measurement of lung function and response to bronchodilator.

Treatment of asthma centres around control of chronic inflammation, avoidance of triggering factors and treatment of acute bronchospasm when needed.

Asthma severity is stratified based on factors regarding symptom frequency and severity, occurrence of nocturnal symptoms, frequency of short‐acting beta‐agonist use, interference with normal activity and objective measurement of pulmonary function. Risk assessment includes frequency of systemic corticosteroid use, and frequency and severity of asthma exacerbations.

Individuals over 65 may have a decreased perception of breathlessness and air hunger. Therefore, the use of clinical symptoms to diagnose and treat seniors may underestimate the severity of airways obstruction.
C
uvier,
G
eorges
Authors: Rudwick Martin JS 
Published: September 2015

Abstract

Georges Cuvier (1769–1832) was a distinguished French comparative anatomist, palaeontologist and civil servant. He defined major groups of animals (now
phyla
) with distinct kinds of anatomy; he showed that many fossil vertebrate species are distinct from any known alive, and he thereby helped establish the reality of extinction as a natural process; and he pioneered the reconstruction of individual fossil species and of the history of life as a whole. He regarded the origins of species and episodes of mass extinction as natural events, but was reluctant to speculate on their causes.