Anemia Autoimmune Hemolytic In Animal Models

C J Elson and C-R Shen, Department of Pathology and Microbiology, University of Bristol, Bristol, UK Autoimmune hemolytic anemia (AIHA) is a classic example of an antibody-mediated autoimmune disease. It is well documented how autoantibody-coated red blood cells (RBCs) can be destroyed by splenic macrophages, but by contrast, the mechanisms that initiate the production of RBC autoantibodies remain unclear. The New Zealand Black (NZB) strain of mice spontaneously develops AIHA. RBC-bound...

The relevance of environmental mycobacteria

Saprophytic mycobacteria are extraordinarily common in the environment, and can be detected in soil samples or scrapings of waterpipes by direct staining and microscopy. Their persistence in the environment is partly attributable to the massive cell wall structure described above. Mycobacteria appear not to be part of the normal commensal microbial flora, but they are ubiquitous, resistant to degradation, and very immunogenic, so skin-test surveys reveal that individuals are sensitized to the...

B cell proliferation

Two major functions of B cells are to secrete immunoglobulins and to bind antigens, process them, and present them to T cells. Each B cell produces immunoglobulins with a single specific antigen-binding site. By virtue of immunoglobulin on its surface (slg), B cells bind specific antigens which then deliver a signal to these cells to proliferate and clon-ally expand into memory cells or to differentiate into Ig-secreting cells. Since only one in 107-108 normal B cells has specificity for a...

Eosinophils in disease

Eosinophils are able to phagocytose immune complexes and microorganisms (e.g. Escherichia coli, Candida albicans, Trypanosoma cruzi), but these capabilities are generally not as great as those of other phagocytes. The ability to release toxic-substances against nonphagocytosable surfaces is probably of greater importance. By this mechanism, eosinophils are able to kill certain metazoan parasites. There is also some evidence to suggest that eosinophil infiltration of tumors increases patient...

Endothelial cell adhesion molecules

The recruitment of leukocytes into sites of inflammation involves a cascade of sequential events controlled by the interaction between adhesion molecules expressed by leukocytes and by the endothelium (Figure 1). This multistep process is a cell-to-cell adhesive reaction that involves specific binding of membrane receptors on one cell to counterreceptor structures on the other cell. Several adhesion receptors belonging to different families, including inte-grins and selectins, have been shown...

Lymph Nodes

CE Grossi, National Institute for Cancer Research, University of Genoa, Genoa, Italy PM Lydyard, Department of Immunology, University College London Medical School, London, UK Lymph nodes are encapsulated organs ranging in size (in humans) from a few millimeters to more than a centimeter, and generally ovoid in shape. They are found as groups of nodules along the lymphatic vessels draining superficial areas of the skin or deep viscera. The bases of the limbs, the neck, the retroperitoneal areas...

IFN3 mediated biological activity

At least five complex types of biological activity are mediated by IFNs 1) receptor binding, 2) antiviral, 3) cell growth inhibitory, 4) immunomodulatory, and 5) antitumor activity. This summary will focus on the first three activities. Any IFN-mediated activity requires binding to a specific receptor on the cell surface. The number of receptors varies from some hundred to a few thousand per cell. All human IFNa species and IFNp share the same type I IFN receptor to which they bind with similar...

Lambert Eaton myasthenic syndrome

This disorder is much less common than myasthenia gravis. It is characterized by proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation and autonomic changes, including dry mouth and constipation. Onset can be in adolescence, but is usually after 40 years of age. Other autoimmune diseases may associate, notably thyroid disease and vitiligo, and other autoantibodies occur at increased frequency. About 60 of cases have associated small cell lung cancer (SCLC). The...

Precipitation in fluids

As mentioned, the phenomenon of immunoprecipitation appears when a solution of antigenic material is mixed with immune serum containing corresponding antibodies. The reaction is registered by a gradually increasing turbidity, changing to the appearance of precipitating or flocculating aggregates. A common procedure for immunoprecipitation analyses is to use a series of test tubes containing a constant amount of one of the reactants, and adding the corresponding reactant in serial, stepwise...

Th1 and Th2 subsets differential roles

This traditional classification has, however, to be seen in the context of the now recognized paradigm establishing the existence of two fundamental Table 1 Classification of immunologic diseases Mechanisms of tissue injury and disease Mast cells and their mediators (vasoactive amines, lipid mediators, cytokines) IgM, IgG antibodies against tissue or cell surface antigen Recruitment and activation of leukocytes (neutrophils, macrophages) Abnormalities in receptor functions Immune complexes of...

Minor Transplantation Histocompatibility Antigens

Elizabeth Simpson, MRC Clinical Sciences Centre, RPMS, London, UK Snell discovered the existence of minor transplantation antigens at the same time that he discovered H2, the major histocompatibility complex (MHC) of the mouse. This discovery came from experiments using the classic genetic approach of crossing, backcrossing and intercrossing two genetically dissimilar inbred mouse strains and examining the ability of tissues from the progeny of these crosses to stimulate a graft rejection...

Monocyte Chemoattractant Protein 1 Mcp1

Claus OC Zachariae, Christian G Larsen and Kouji Matsushima, Department of Haemotology, Herlev Hospital, University of Copenhagen, Denmark Monocyte chemoattractant protein 1 (MCP-1) is encoded by human chromosome 17qll.2-q21.1 and is also known as MCAF (monocyte chemotactic and activating factor). MCP-1 belongs to the chemokine p family as it has a C-C (cysteine-cysteine) amino acid sequence, as opposed to the C-X-C structure of the chemokine a family to which interleukin-8 (IL-8) belongs. The...

Lysozyme

Lysozyme was described by Fleming, who noted both its wide distribution and its remarkable ability to lyse certain gram-positive bacteria, such as Micrococcus lysodeikticus. Lysozyme is a very cationic protein of approximately 14.4 kDa. Its enzymatic activity is directed against the (31-4 glycosidic bond between N-acetylglucosamine and N-acetylmuramic acid resi dues, which stabilizes many bacterial cell walls. Not only is lysozyme a component of PMN, monocyte and macrophage granules, it is also...

Characteristics of Histoplasma capsulatum and its antigens

The pathogenic fungus, Histoplasma capsulatum, exists in nature as a filamentous organism that produces two asexual spores, microconidia and tubercu-late macroconidia. The natural habitat of the organism is soil enriched by bird droppings. Chromosomal mapping studies of this fungus have revealed substantial variability in the genomic organization of H. capsulatum strains. The Downs strain, which is ther-mointolerant, possesses seven chromosomes, whereas two thermotolerant strains, G217B and...

Attenuated Organisms As Vaccines

Konstantin M Chumakov, Center for Biologies Evaluation and Research, Food and Drug Administration, Maryland, USA Attenuation is a process of genetic changes leading to a loss of virulence by pathogenic microorganisms while retaining the capacity to induce an immune response in susceptible hosts, resulting in lasting protection from a disease. Attenuation is a part of the natural evolution of pathogenic microorganisms, and is used by man to create 'live' vaccines against infectious diseases...

Cell and molecular biological studies of suppressor cells

The studies mentioned above plus numerous others clearly established that the concept of cell-based negative regulation had merit. Furthermore, the phenomenology of suppression could be demonstrated in virtually all types of immune responses. The challenge became to establish the physiological, biochemical and molecular genetic basis of suppression. The major questions that required study-were as follows 1) Does there exist a phenotypically and biologically distinct population of lymphocytes...

What is MIF

The original definition of MIF as an activity mav not be as useful as it once was. Many factors are now recognized which can influence random migration in different cell types. The focus of most attention has now shifted to a protein which carries on the name MIF, even though this may not turn out to be completely appropriate. MIF does seem to be able to inhibit macrophage migration, but it also has several other, perhaps more important, roles in immunology and in other areas of biology. Does...

Further reading

Bach EA, Tanner JW, Marsters S ft al (1996) I.igand-induced assembly and activation of the gamma interferon receptor in intact cells. Molecular and Cellular Biology 16 3214-3221. Bluyssen HAR, Durbin JE and Levy DE (1996) ISGFVy p48, a specificity switch for interferon activated transcription factors. Cytokine and Growth Factor Reviews 7 11-17. Boehm U, Klamp T, Groot M and Howard JC (1997) Cellular responses to interferon-gamma. Annual Review of Immunology 15 749-795. Bottazzo GF,...

Info

These are generally also loosely included under the term 'ANA'. One of these cytoplasmic antigens is called La SS-B. It functions as a termination factor for RNA polymerase III. Therefore, La SS-B scRNPs are composed of an RNA polymerase III transcript to which the La SS-B protein is bound (Figure 3). The RNA transcripts include 7S RNA, 5S RNA, tRNA, U6-RNA, the Y-RNAs as well as a number of viral RNAs. Ro SS-A scRNPs are composed of several proteins complexed with a subset of the La SS-B...

B cell differentiation in peripheral lymphoid tissues

B cell differentiation in the peripheral lymphoid tissues is predominantly antigen driven. B cell antigens can be broadly divided into thymus dependent (TD) and thymus independent (TI). TD antigens are usually soluble protein antigens that require major histocompatibility complex (MHC) class II-restricted T cell help for antibody production while TI antigens do not require such help, and are often multivalent and poorly degraded in vivo. Good examples of TI antigens are bacterial...

Thymic peptides as immunoregulators or biological response modifiers

As mentioned above, only thymulin can today be described as a classical hormone. Nevertheless, further investigations are required regarding the physiological relevance of the numerous data showing immunological effects of thymic peptides. 1) Between 400 and 800 pg ml Tal (or ProTa, this fact remains to be elucidated), 300-500 ng ml thymopoietin and 0.5-3 pg ml thymulin are present in human plasma. THF has also been detected. Except for thymulin, these levels are not reduced by thymic...

Characteristics of the organism and its antigens

The causative agent of toxocariasis is the nematode, or 'roundworm', parasite Toxocara canis. Infective eggs are released by sexually reproducing adult worms which parasitize the intestines of domestic dogs and related carnivores. The eggs are not initially infective, but require a period of 2-3 weeks for the development of infective larvae. These are contained within characteristically pitted eggs which are extremely resilient, and viable eggs can persist in soil for many years. Infection is...

Pathophysiology

Table 2 is an incomplete listing of the various physiological systems involved in the pathophysiology of sepsis. A theory has evolved comprising successive waves of mediators and events which might result in lethality. In a first stage, bacterial products Figure 1 Interrelationship between systemic inflammatory response syndrome (SIRS), sepsis and infection. blood-borne infections (Reproduced with permission from Bone et al (1992).) Bacterial factors Lipopolysaccharide Peptidoglycans Exotoxins...

Immunotherapy Of Autoimmune Diseases

Marc Feldmann and Ravinder N Maini, Kennedy Institute of Rheumatology, London, UK The term 'immunotherapy' is used in two somewhat different senses. One is 'therapy of the immune system', aimed at targets ranging from antigen-presenting cells to activated T cells, macrophages and B cells. Another context is the use of immunological reagents, such as antibodies, T cells or their modifi cations in therapy. Immunotherapy in both senses has been applied vigorously in animal models of autoimmune...

Roles outside the immune system

Aside from its role as a secreted factor in the immune system, there is evidence for an intracellular mode of action for MIF in many cell types. MIF is widely expressed in many tissues regardless ot immune status, including immunologically privileged sites such as the lens and brain. MIF was identified as a highly abundant protein associated with cell differentiation in the acapsular, immune-privileged eye lens in the embryonic chick. It was also cloned from human and mouse lens, confirming its...

Structure and expression of the IL2R

Subunit composition of the three IL-2R complexes The IL-2 molecule has a four a helix bundle structure characteristic of many cytokines and, from molecular modeling and mutational studies, is thought to contain distinct binding sites for each of the three IL-2R chains. Depending on which subunits are expressed by a cell, three distinct forms of the IL-2R can be detected. The high-affinity IL-2R (Kd 5-10 pM) is found on activated lymphocytes and consists of an a 3 yc trimeric complex (Figure 1)....

Autoimmune bullous dermatoses

Since the recognition of circulating antibodies against skin components as well as antibody deposition in the skin of pemphigus and pemphigoid, a large number of immunological studies have been performed to identify the precise subtypes of these presumed autoantibodies, their role in pathogenesis, and the antigens to which they bind in the skin. It has become apparent that the most important group of autoimmune skin diseases is characterized by blister formation as a result of interference by...

Features of the immune response to specific types of pathogens within the CNS

Viruses invade the CNS through hematogenous dissemination or by retrograde transport up neurons that have processes extending into sites of infection in the periphery. As intracellular pathogens, their tropism for different neural cells and effect on host cell function determine the severity of disease. The paucity of MHC antigen expression within the CNS can make the cytotoxic T lymphocyte (CTL)-mediated clearance of viruses difficult and may predispose to chronic or relapsing infections....

Experimental models of serum sickness Acute serum sickness

This is the classical serum sickness model and is also known as acute immune complex disease. It is normally induced by a single intravenous injection of xenogeneic protein - most commonly bovine serum albumin (BSA) (250mgkg ') into rabbits. Antibody-is formed and binds to circulating antigen to form immune complexes. These complexes are observed in the sera and from day 10 there is no detectable antigen in the circulation. The events occurring in the 2 weeks following radiolabeled antigen...

Platelet antigenicity

GPIb is a target on the platelet surface for the attachment of quinine quinidine drug-dependent antibodies. The result of this drug-antibody binding to (or near) platelet GPIb molecules is usually severe thrombocytopenia. Some patients with 'idiopathic' autoimmune thrombocytopenic purpura (ITP) make autoantibodies that are directed against antigenic components of either GPIb or, more commonly, the GPIIb-IIa complex. The platelet-specific alloantigens Leka and P1A1 are located on GPIIb and Ilia,...

Is there tolerance to ocular antigens

Central to the understanding of the mechanisms of ocular autoimmunity is the special localization of the ocular antigens in relation to the immune system. It has long been known that the eye is an 'immunologically privileged' organ, such that histoincompatible tissue grafts placed in the anterior chamber of the eye are not rejected. The reason for this immune privilege has been attributed mainly to the fact that there is no lymphatic drainage of the interior of the globe, and to the existence...

IgA in mucosal host defense

IgA is quantitatively the most important of the immunoglobulins, having a synthetic rate exceeding that of all other immunoglobulins combined when secretory as well as circulating IgA is taken into account. In humans it is encoded by two genes within the immunoglobulin gene locus on chromosome 14. The 5' IgA gene encodes IgAl, the predominant circulating IgA and a major component of the IgA in mucosal secretions. The more 3' IgA gene encodes IgA2, the IgA that is particularly abundant in...

Biological activities of IL11

IL-11 is a bone marrow fibroblast-derived cytokine with a variety of in vitro biological activities within the hematopoietic, lymphopoietic, hepatic, adipose, bone and neuronal systems. IL-1 I has been tested in various animal models including mice, rats, hamsters, rabbits and nonhuman primates. Some of these in vitro and in vivo studies are summarized in Tables 2-4. It appears that IL-11 may be a potential therapeutic agent for thrombocytopenia and neutropenia following myeloablative therapy...

Q

Figure 2 The beneficial effects of anti-inflammatory therapy on frequency, duration and severity of exacerbations in asthma. Figure 2 The beneficial effects of anti-inflammatory therapy on frequency, duration and severity of exacerbations in asthma. twice a month, and a resting peak expiratory flow rate (PEFR) of > 80 of predicted with less than 20 diurnal variability. Moderate asthma is defined as exacerbations more than twice a week, resulting in urgent care treatment less than three times...

Organization of the mucosal immune system

In order to understand how mucosal immunity occurs, it is important to appreciate that foreign antigens, allergens and microbial pathogens arc encountered either through ingestion or by inhalation. The mammalian host has thus evolved organized second ary lymphoid tissues in these regions, which facilitate antigen uptake for processing and presentation for ultimate induction of mucosal immune responses. In mice, rats and rabbits (among others), a distinct BALT occurs which appears to take up and...

Primary Biliary Cirrhosis

M Eric Gershwin, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, California, USA Ian R Mackay, Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria, Australia Primary biliary cirrhosis (PBC) is an enigmatic chronic liver disease characterized by progressive inflammatory obliteration of the intrahepatic bile ducts. Clinical features and laboratory studies of the disease include data suggesting an underlying...

Immunodeficiencies and oral health

The oral cavity can be considered a window to the health and immune status of an individual. Although the oral cavity is anatomically unique, it enjoys both the benefits and liabilities of systemic immunity. Perturbations of the T cell compartment of the immune system are often indicated by oral mucosal infections by opportunistic microorganisms, resulting in oral ulcerations. Children with severe combined immune deficiency (SCID) have rampant growth of Candida albicans on their oral mucosal...

Autoimmune renal disease

One of the more interesting effects of mercury is the induction of autoimmune renal disease. In rabbits, and certain susceptible rat (BN, Wistar, MAXX, PVG and other) and mouse (A.SW, SJL, BALB c and C3H.NB) strains, mercury may induce an autoimmune glomerulonephritis. In humans, the glomerular dysfunction caused by mercury has also been suggested to have an autoimmune component. In susceptible laboratory strains the disease is associated with T lymphocyte-dependent polyclonal B cell...

Fish Immune System

Fish Immune Organ

A E Ellis, SOAEFD Marine Laboratory, Aberdeen, UK It is important to realize that among the Vertebrata, the class Pisces has within it the oldest and most numerous species. The most recent and evol-utionarily advanced group of fish, and the one of most commercial importance, is the teleosts (bony fish), which first appeared in the late Devonian Age, 300 million years ago, and rose to prominence 70 million years ago. Now they are the most numerous with over 20 000 extant species (compared with...

Feline Immune System

Ian R Tizard, Department of Veterinary Pathobiology, The Texas Veterinary Medical Center, Texas A& M University, Texas, USA The immune system of the cat possesses no unique structural elements and it is safe to assume that in its basic features it conforms to the pattern seen in other placental mammals. Nevertheless, the feline immune system does show some interesting and unique differences, described here. Cats, like ruminants and pigs, possess a population of pulmonary intravascular...

Clinical phenotype of human SCID

As expected from the severe defects affecting both cellular and humoral immunity, SCID patients commonly have persistent and recurrent infections. Patients with SCID often present with oral candidiasis, diarrhea, otitis, sepsis, cutaneous infections and pneumonia. Failure to thrive is observed secondary to chronic infection, malabsorption and diarrhea. Patients often suffer from infections by opportunistic microorganisms including Pneumocystis carinii, Cryptosporidia and Candida albicans....

Antigenic shift and drift in the influenza viruses

Among the influenza A viruses, both of the surface glycoproteins (the hemagglutinin and neuraminidase) undergo two types of variation antigenic drift and antigenic shift. Antigenic drift involves minor changes in the antigenicity of the surface protein and is thought to be responsible for the persistence of the virus in a susceptible population. Antigenic shift involves major genetic changes that are responsible for the development of the 'new' viruses in the host species. Antibodies to the...

Antibodies against plasma proteins

Most important are antibodies against IgA, which mainly occur in IgA-deficient subjects. Most of the antibodies are directed against nonpolymorphic epitopes on the al or a2 chains but anti-allotypic (A2m) antibodies may also occur. The interaction of these antibodies with donor IgA, even if very small quantitites are transfused, can cause a severe anaphylactic reaction which may be fatal. Patients with such antibodies can be transfused with red celis which have been washed six times. For other...

Myasthenia gravis

The dominant clinical feature is fatiguable weakness of skeletal muscle, typically affecting the ocular muscles early in the disease, and bulbar, limb, trunk and respiratory muscles in severe cases. MG appears to affect all races, the prevalence in the Western world being about 5-9 per 100000 with an annual incidence of about 4 per million. It may occur from early childhood to extreme old age. Other autoimmune diseases occur at increased frequency, especially thyroid disease, and other...

Nonspecific defenses

Nonspecific recognition of common bacterial structures Much of the defense against bacteria depends on pathways which have nothing to do with the specific antigen receptors of either B cells or T cells, and probably antedate these in evolution. Many bacteria are simply excluded by barriers such as skin, acidity in gut and vagina, commensals occupying the relevant niche, entrapment by mucus, etc. If not excluded, the organism may be recognized by 1. Acute phase proteins, C-reactive protein and...

Antigens

Michael Sela, Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel Antigen is any substance (molecule) that provokes the production of specific antibody or immunocyte (immune cell), or that interacts specifically with these products of the immune response, when penetrating the body of a vertebrate. The first part of this definition, namely, the capacity to provoke an immune response is also called immunogenicity and the substance provoking such a response is...

Scleroderma

Scleroderma is a chronic disease with variants limited to the skin only and systemic forms. Systemic scleroderma is discused elsewhere in this volume. From a dermatological point of view, subvariants of systemic scleroderma include progressive systemic sclerosis, CREST-syndrome, and mixed connective tissue disease (MCTD). Cutaneous variants of this disease are also known as localized scleroderma, but generally called morphea. Essentially, in cutaneous manifestations of scleroderma, there is an...

Lymphocyte proliferation the cell cycle

Conceptually, the cell cycle process occurs in a series of phases (Figure 2). Fundamentally, these exist to ensure that DNA replication and chromosome segregation are completed with high fidelity. Cells must ensure that chromosome duplication and segregation occur in the correct order, and that segregation only occurs after all sister chromatids are aligned on the mitotic spindle. Another concept is that cells have evolved surveillance mechanisms or 'checkpoints' to ensure that critical...

Ovine Immune System

Ian McConnell and John Hopkins, Department of Clinical and Veterinary Medicine, University of Cambridge, Cambridge, UK The ovine immune system occupies a special place in immunology because the sheep is the best species for investigating the physiology of the immune system. The trend to reductionism in modern immunology, which is facilitated by the ease with which the cells of the immune system can be disaggregated from lymphoid tissue and studied in vitro, has meant that much of our knowledge...

Graphical methods

Data analysis is enhanced by visual displays of the data. Although there is a large repertory of graphical techniques available, the following methods are those commonly used and informative in the understanding of immune response data. Examples of these graphs can be found among the references suggested for further reading. Histogram (frequency distribution, bar diagram) This graph is a simple, well-known tool for visualizing many types of data. Histograms are especially useful as one of...

Autoimmune features of vitiligo

Vitiligo can be found in autoimmune families in association with Addison disease, alopecia areata, pernicious anemia, or mucocutaneous candidiasis, with an incidence 10-15 times higher than in the general population. Antibodies to thyroid, adrenal gland and gastric parital cells can be demonstrated in vitiligo patients using modern techniques, antibodies reactive with melanocytes have been consistently-found in vitiligo patients' sera. The levels of these antibodies are greatest in patients...

Immunoelectrophoresis

Anna-Brita Laurell, Department of Medical Microbiology, Section of Clinical Immunology, University of Lund, Lund, Sweden The term immunoelectrophoresis, or electroimmuno-precipitation, which is sometimes used synonymously, refers to any of a series of methods where immunoprecipitation is obtained after electrophor-etic separation of proteins in an electric field. Based on differences in antigenic composition and charge, these methods make possible identification and quantification of proteins...

Monitoring of hapten binding

Monitoring is carried out in basic immunology, usually to determine affinity of antibodies, and in clinical chemistry, forensic science, etc., to quantify substances of low concentration. The gold standard for measuring the affinity of a hapten-specific antibody is equilibrium dialysis. It requires that the concentration of specific antibody is known and that the concentration of the hapten can be determined at the concentration range where half saturation of antigen-binding sites occurs...

Animal models of autoimmune gastritis

Spontaneously occurring autoimmune gastritis There is no animal model in which the primary disease is autoimmune gastritis although atypical forms of autoimmune gastritis are present in a proportion of animals whose primary autoimmune disease is one of the diseases associated with autoimmune gastritis. For example BB W rats whose primary disease is insulin-dependent diabetes mellitus may have gastric parietal cell antibodies and histologic evidence of mild to moderate gastritis. However they...

The use of immunological techniques in the study of disease

Traditionally, the basis for this 'investigative immunopathology' is serology. Detection of antibody against a specific pathogen, and of rising (or falling) titers of antibody, has long been the mainstay of the approach. The concept of autoimmunity is heavily based upon the identification of circulating antibodies directed against intrinsic antigens, and there is also reciprocal serology, based upon the use of antisera to detect a given antigen. There are now many ways to detect and amplify the...

B cell deficiency diseases

The physiological importance of B cell function is revealed by diseases that result from selective B cell deficiencies and consequent lack of antibodies (agammaglobulinemia). Bruton's agammaglobulinemia (XLA) is an X-linked defect in B cell maturation in humans, with arrest at the Pre-B I stage and a resulting deficiency in all immunoglobulin classes. A corresponding B cell maturation defect, the Xid mutation, also occurs in CBA N mice. In male children with XLA, the maturation block results...

Vaccines

In 1798, Edward Jenner published results of his experiments which showed that previous infection with cowpox - variolae vaccinae - protected humans against challenge with smallpox. Although the original observation can be traced back to country folklore, Jenner was the first to test the hypothesis scientifically. He had also to contend with the difficulty that cattle could be infected with either cowpox, an orthopoxvirus which did protect, or the clinically similar pseudocowpox, a parapoxvirus...

Phylogeny Of The Immune Response

Norman A Ratcliffe, Biomedical and Physiological Research Group, School of Biological Sciences, University of Wales, Swansea, UK In comparison with vertebrates, the immune response of invertebrates is extremely limited. Specific antibody produced by interactive lymphocyte subpopulations together with extremely finely tuned discrimination of self from nonself and a high degree of memory are confined to the vertebrates, and yet, invertebrates comprise over 95 of all known species of animals....

Thyroiditis

Patients with chronic autoimmune thyroiditis most commonly present with clinical and or biochemical evidence of thyroid failure with or without goitre. Clinically they can be divided into those with goitrous (Hashimoto's) thyroiditis and those with atrophic thyroiditis (primary myxedema). Historically, establishment of their autoimmune basis has relied on the presence of autoantibodies to thyroglo-bulin (in the minority) and to the thyroid microsome (in the majority), detected by...

Other mechanisms of action of NSAIDs

While there is very strong evidence supporting the hypothesis that NSAIDs produce their antiinflammatory, analgesic, antipyretic and antithrombotic effects through inhibition of prostanoid synthesis, there is also evidence for other mechanisms of action. These other mechanisms of action may explain the differences in activity from one NSAID to another. For example, NSAIDs such as indomethacin have been shown to inhibit other enzymes, including phospholipase A2, diacylglycerol kinase and...

Proinflammatory effects of NSAIDs

Ironically, while prostaglandins are typically described as mediators of inflammation, these substances exert a wide range of anti-inflammatory effects (Figure 3). For example, prostaglandins are potent inhibitors of the release of tumor necrosis factor a (TNFa) and IL-1 from macrophages, and potent inhibitors of TNFa and platelet-activating factor from mast cells. Prostaglandins also suppress the release of a number of proinflammatory mediators from platelets. On the other hand, NSAIDs, by...

Implications of determinant spreading for immunotherapy

Knowledge about the temporal pattern of appearance of new T cell specificities directed against determinants within the same or different antigens is crucial in designing appropriate therapeutic strategies. Therapeutic approaches based primarily on controlling T cell responses to the initial disease-inducing determinant may not succecd if spreading of response has already occurred. Tolerance induction with peptides comprising encephalitogenic determinants appearing later in the disease may...

Cytokines a bridge between the nervous system and the immune system

Cytokines are cell-derived peptides that may modify the functions of the cells that secrete them, as well as the functions of other cells that have receptors for them. Table 2 lists a number of cytokines that are produced and act in both the nervous system and the immune system. Some of our initial knowledge of cytokines that are produced by cells outside the nervous system but that have an apparent effect within the nervous system came from clinical observations. One early study demonstrated...

IL2 in the negative control of lymphocyte proliferation

Autoimmunity in IL-2-deficient animals The precise role of IL-2 in vivo is not well understood. An important tool for studying this question is provided by gene knockout mice produced after homologous recombination. In IL-2_ animals the ontogeny of the immune system is not dramatically affected, as demonstrated by the normal development of lymphoid organs and the presence of the major lymphocyte subsets. However IL-2_ animals have an overproduction of lymphocytes, which is morphologically...

Immune response of the host

Circulating antibodies in infected pigs can be detected by radioimmunoassay or ELISA 3-4 days after infection and they persist for life. Neutralizing antibodies have never been demonstrated. After recovery from infection with less virulent isolates, pigs are persistently infected for at least 6 months and are resistant to challenge with homologous virus, although the challenge virus may undergo limited replication without producing clinical disease they are usually fully susceptible to...

Mechanisms of immunopathology

Septicemic shock and the adult respiratory distress syndrome The cytokine release triggered by bacterial components has a protective and immunoregulatory role as described above, but when excessive, as during septicemia, there can be excessive systemic activation of phagocytes and of endothelial cells. The latter leads to adhesion of phagocytes to the endothelium, initiation of the clotting cascade via expression of tissue thromboplastin, and eventually to diffuse intravascular coagulation that...

The goal of selective immunosuppression

If any foreign material (antigen) makes its way into the body - virus, bacteria, fungi or parasites - a swift and complex immune response for destroying it is set into motion. The allelic products of the major histocompatibility complex (MHC) characterize the immunological identity of each individual. With the exception of identical twins, it is extremely unlikely that two individuals match exactly. Nature did not intend for organs to be transplanted from one individual to another. The speed...

Molecular basis of attenuation

A reduction in pathogenicity can occur either through the loss of external pathogenic factors (toxins), as is the case with some bacterial vaccines, or by impairing the invasiveness of a pathogen and limiting its access to target organs. In many cases attenuating mutations occur in capsid or envelope proteins of a virus, presumably reducing its affinity for the target cells. Detailed studies of attenuated polioviruses identified a number of mutations that distinguished vaccine viruses from...

Mechanisms of changes in reptilian immune system

Body temperature is a salient factor regulating the performance of reptilian immunological functions. It must be noted in this regard that reptiles, in contrast to fish and amphibians, have become restricted in the temperature range over which physiological activities, including immune responses, can occur. Photo-periods, humidity and nutrition are also critical modulators of reptilian immune processes. Endogenous rhythmic factors that are not as yet characterized appear also to control immune...

Stressorassociated regulation of immunity

Stress, as defined by Hans Selye, is the response to deviation from the normal resting condition (i.e. homeostasis). It is generally accepted that stressor administration causes complex neurologic and neurochemical changes as the host attempts to adapt to the demands of the situation. These CNS changes regulate many physiologic processes, including those involved in the generation of an immune response. Immunomodulatory 'stress' protocols have involved different periods of exposure to either...

Phenotypic expression of a single gene

In addition to the common polymorphisms not associated with any obvious phenotypic abnormalities, there are several examples of phenotypic disorders associated with genotypic changes in a single gene. These disorders are commonly referred to as single-gene or monogenic disorders. In these disorders, phenotypic variability is primarily determined at the corresponding gene locus and the effect of other loci and environmental factors, although they may be present, is not the major determinant....

Functions of LIF

LIF was identified as a factor capable of inducing the terminal differentiation of the murine myeloid leukemic cell line Ml into macrophages. Activation of the transcription factor STAT3 is essential for LIF-induced differentiation of Ml cells. A number of myeloid leukemic cell lines, which were unresponsive to treatment with LIF, expressed various defects in the JAK STAT signal cascade, suggesting modulations of this pathway to be a crucial step in leukemo-genesis. Although LIF expressed...

Vitamin C And The Immune System

Reto Muggli, Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan Ascorbic acid (vitamin C) is required for the optimal functioning of all cells, tissues, and organs. It is the most important water soluble antioxidant and is a cofactor in many hydroxylating reactions. Man, primates, guinea pigs and a few other species lack the capability to synthesize ascorbic acid, for them ascorbic acid is an essential nutrient. There is abundant evidence from...

Characteristics of the acquired immune response

The first time an antigen enters the body a wide spectrum of events occurs. The antigen is usually contained at the site of entry and in nearby lymph nodes by various phagocytic cells such as macrophages and dendritic cells. These cells process the antigen and present pathogen-derived peptides to CD4+ and CD8+ T cells in association with major histocompatibility complex (MHC)-encoded molecules. Antigen binding by surface immunoglobulin and cognate help by CD4+ T cells induce B cells to...

Mtppe

Figure 3 Chemical structures of various MDP derivatives applied to clinical trials. adjuvanticity but shows no substantial activity regarding nonspecific resistance to infection. Clinical trials using B30-MDP as an adjuvant effect in an influenza virus vaccine demonstrate that it is able to induce both humoral and cellular immunity. MTP-PE has been shown to be highly effective in generating tumoricidal properties of macrophages. Lipo-some-encapsulated MTP-PE (L-MTP-PE) has been designed for in...

Antiinflammatory and immunosuppressive effects

Suppression of inflammatory and immune reactions and treatment of cancers of the lymphoid system are among the major applications of glucocorticoids. As noted above, despite early assumptions that such 'pharmacological' effects had no physiological basis, it is now clear that they are as physiological as are the effects on glucose metabolism. For example, induction of adrenal insufficiency in experimental animals (by adrenalectomy or administration of the glucocorticoid antagonist RU486)...

Lifespan of lymphocytes in humans

All of the figures discussed so far in this entry refer to the rodent immune system. There is some evidence that both T and B lymphocytes may live much longer in humans. Studies in patients who have either accidentally, or in the course of treatment, received a heavy radiation dose resulting in characteristic chromosome breakages that preclude mitosis, indicate that lymphocytes can persist for upwards of 10 years without dividing, although the damage to the DNA may itself have caused such...

Cooperation Mechanisms Of Cellular

Theodore J Yun, Department of Microbiology, University of Washington, Seattle, Washington, USA Edward A Clark, Departments of Microbiology and Immunology, University of Washington, Seattle, Washington, USA Various pathogens, ranging from viruses to helminths, can invade the host by a number of pathways, and usually the pathogen is cleared through an orchestrated immune response. Moreover, protection from a repeat infection is provided by a memory response, which, relative to the primary...

Nature of antigenantibody intermolecular forces

Also known as electrodynamic interactions, these occur universally between all atoms and molecules, when brought close enough together. Three different but related phenomena contribute to van der Waals interactions 1) randomly orienting dipole-dipole (orientation) interactions, or van der Waals-Keesom forces 2) randomly orienting dipole-induced dipole (induction) interactions, or van der Waals-Debye-forces 3) randomly fluctuating dipole-induced dipole (dispersion) interactions, or van der...

Hepatitis F viruses

Serologic testing has identified five hepatropic viruses HAV, HBV, HCV, HDV and HEV. These viruses account for almost all human viral hepatitis however, a small percentage of patients exhibiting the signs and symptoms of acute viral hepatitis do not have serologic evidence of infection with any of these viruses. Researchers continue to search for the viruses associated with non-ABCDE hepatitis. Many of these enterically and parenterally transmitted viruses have been tentatively designated...

Radiosensitivity of cellular components of the immune system

The type and magnitude of specific immune responses is determined by the interaction of antigen-presenting cells such as dendritic cells and macrophages with T and B lymphocytes. However, the effector arms of the immune system depend on interactions of numerous leukocyte subsets. In addition to lymphocytes and macrophages, natural killer (NK) cells, eosinophils and granulocytes contribute significantly to host resistance to infections. Macrophages are relatively radioresistant, as are other...

Virulence factors

A number of specific proteins encoded by chromosomal genes have been implicated as virulence factors that allow P. mirabilis to colonize its host, evade host defenses, and cause damage to the host (Figure 3). The production of one of these proteins, urease, is a hallmark of Proteus infection. This enzyme, which catalyzes the hydrolysis of urea to carbon dioxide and ammonia, elevates urine pH to a level where normally soluble ions precipitate to form struvite or apatite stones. These stones,...

The immune response to infections

The development of vaccines has been based on two requirements safety - the product should not induce undue morbidity and efficacy - immunization should prevent clinical disease on subsequent exposure to the wild-type agent. Other than measurement in relatively recent times of specific antibody levels and particularly a functional test such as neutralization of infectivity, generally no other parameters of the immunogenicity of the product were considered. Most current vaccines are to 'acute'...

Mechanisms of oral tolerance

The primary mechanisms by which oral tolerance is mediated include deletion, anergy and active cellular suppression with the determining factor being the dose of antigen fed (Figure 2). Low doses favor active suppression mediated by the induction of regulatory T cells in the gut-associated lymphoid tissue, such as Peyer's patches, which then migrate to the systemic immune system. When higher doses of antigen are fed, clonal anergy or deletion results. Active cellular suppression of immune...

Binding properties of class Ii Mhc molecules

The binding properties of class II MHC molecules can be studied using purified molecules, usually in detergent solutions, or directly in the APC. Purified class II molecules bind peptides in a homogeneous saturable process with binding affinity constants in the 10A-10 S m range. The rate of association of peptide with the MHC molecule is slow, but once the peptide is bound it can form a very stable and long-lived complex. The complex of MHC with peptide can be assembled and isolated in free...

B cell superantigens

Other microbial substances act as superantigens by binding to the B cell antigen receptors outside the antigen binding site. Staphylococcus aureus-& er'wzd protein A is the prototype for this interaction at the B cell level. Polymerized protein A induces strong B cell proliferation and Ig secretion in conjunction with cytokines such as IL-2. Superantigens are polyclonal activators but, rather than stimulating protective immunity, they could deviate the B cell response away from important...

Reptilian Immune System

Rashika El Ridi, Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt Reptiles evolved from primitive amphibians nearly 300 million years ago during the Carboniferous period. They sprang from a basic stock, the long-extinct order Cotylosauria or 'stem reptiles'. A side-branch of stem reptiles led to the turtles and tortoises order Testudines Chelonia. The closest surviving descendants of the cotylosaurs are the tuatara that live on a few islands off New Zealand. Descended from...

Hepatitis G virus

Recently, a new hepatitis-associated virus, hepatitis G virus (HGV), has been cloned and sequenced. HGV, an RNA virus, is a member of the Flaviviridae family, and is distantly related to HCV. Originally this virus was one of the viruses referred to as HEV. Although HGV has been identified as a hepatitis-associated virus and is associated with acute and chronic hepatitis, research has failed to prove that HGV is hepatotropic. At this time no serologic test exists for detection of HGV-infected...

Interaction with CD2

Initially, LFA-3 was defined by the ability of a monoclonal antibody (mAb) to block human cytolytic T lymphocyte (CTL)-mediated lysis by binding to the target cell surface. However, even before this discovery, a method widely used by immunologists to purify human T cells by forming rosettes with sheep red blood cells utilized the molecular interaction between LFA-3 and its ligand. The CTL-mediated lysis of targets as well as T cell rosetting was also inhibited by mAbs which bound to CD2 on the...

Fetus As Allograft

Peter M Johnson, Department of Immunology, University of Liverpool, Liverpool, UK Copyright 1998 Elsevier Ltd. All Rights Reserved. Modern considerations of the haplo-nonidentical fetus as an allograft in outbred pregnancy have developed from initial postulates, put forward by Medawar, Brent and Billingham in 1953, that were derived from their work on transplantation tolcr-ance. In these, they proposed that I) the conceptus may not be immunogenic, 2) pregnancy may alter the immune response, 3)...

T Cell Receptor Recognition By

Arthur W Boylston, Department of Pathology, University of Leeds, Leeds, UK Unlike antibodies, T lymphocytes do not recognize antigens in solution. Instead, they recognize antigens on intact cells in the context of surface molecules encoded by the major histocompatibility complex (MHC). How cells could recognize both a foreign antigen and MHC proteins was the central problem in immunobiology for many years. The answers to this problem have come from elucidation of the structure of the T cell...

Newer approaches to vaccine development

There are a great variety of diseases - viral, bacterial and parasitic - for which no vaccines are available. The need is great five parasitic diseases alone affect about one-quarter of the world's population. Reasons such as the inability to grow sufficient of the organism either in vitro or in an animal, the complex nature of the infectious process (often including substantial suppressor effects), a lack of understanding of the basis of many chronic and persisting infections, all contribute...

Effector mechanisms

As to effector mechanisms, autoimmune diseases are no different from any other pathogenic immune response against foreign antigens involving reactions of types II (cytotoxic antibodies), III (immune complexes), IV (cellular-mediated immunity) and V (stimulating antibodies) according to the Gell Coombs nomenclature. Furthermore, antigen nonspecific mechanisms secondarily activated by auto-antigen-activated lymphocytes play an important pathogenetic role. The detection of circulating and or...

Insulindependent Diabetes Mellitus Experimental Models

Ji-Won Yoon and Hee-Sook Jun, Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada Institute for Medical Science, Ajou University School of Medicine, Suwon, Korea Copyright 1998 Elsevier Ltd. All Rights Reserved. Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM), results from the destruction of insulin-producing pancreatic (3 cells, culminating in hypoinsulinemia...

Immune Response Ir GENES

Jerold G Woodward, Department of Microbiology and Immunology, University of Kentucky Medical Center, Kentucky, USA Immune response (Ir) genes can be defined as any gene locus at which different alleles affect the magnitude of an immune response. Thus, Ir genes were identified on the basis of a complex phenotype and, not surprisingly, comprise a heterogeneous group of structural genes. Nevertheless, genes encoded within the major histocompatibility complex (MHC) clearly have the most dramatic...

CTL target cells

Following the demonstration of the requirements for MHC compatibility for macrophage T lymphocyte interaction and for T lymphocyte B lymphocyte interaction, it was shown by Zinkernagel and Doherty for virus-infected cells, by Shearer for targets modified with the TNP (trinitrophenyl) hapten, and by Bevan for targets bearing minor histocompatibility antigens, that the killing of antigen-bearing target cells by CD8+ T cells was also restricted by MHC antigens. In the virus studies, mice were...

Classification of idiotypes

Idiotypes are generally defined by serologic reagents collectively designated as anti-idiotype antibodies. Several criteria were used to classify the idiotypes based on the type of interaction between idiotypes and anti-idiotype antibodies. The immunochemical criterion used to classify the idiotype consists of the effect of antigen on the interaction between idiotype and anti-idiotype antibodies. In the case of some idiotypes, this reaction is inhibited by the antigen, whereas in other cases it...

Structural organization of the mucosal immune system

Lymphocytes associated with mucosal sites arc located in three major compartments 1) organized tissue such as the Peyer's patches, BALT, tonsils, mesenteric lymph nodes and appendix 2) the nonorganized lymphoid cells present diffusely throughout the lamina propria and 3) the lymphocytes present within the mucosal epithelium, the intraepithelial lymphocytes (IELs). Lymphoid cells in organized structures such as the Peyer's patches are thought to be primarily less mature cells that play an...

Contraception Immunological

GP Talwar, International Centre for Genetic Engineering and Biotechnology, New Delhi, India A major technological advance in the twentieth century was the development of a number of methods to prevent an unwanted pregnancy. Amongst newer methods currently under development are those which employ immunological approaches. Vaccines inducing appropriate immune response have been made, with demonstrated ability to control fertility in experimental animals, including subhuman primates. Extensive...

Diversity of acute phase proteins

There is considerable diversity among acute phase proteins with respect to the concentrations attained, their structures, their behavior in different species and in different diseases. The concentration of a plasma protein depends on the balance between its secretion rate and its clearance rate. The availability of the protein for a particular function is the important factor in physiological and pathophysiological situations, rather than simply its serum concentration measured ex vivo....