Evasive strategies by the organism

A key feature of chlamydiae is their unique replication cycle and their ability to replicate inside host cells. Obviously, growth intracellularly protects the organism to some extent from antibody although the elementary body is susceptible to neutralization. In order to survive in the host cell, the organisms have developed a mechanism for preventing phagosome-lysosome fusion. Nevertheless, the prevention of phagosome-lysosome fusion is overcome when chlamydial elementary bodies are opsonized...

Systemic Lupus Erythematosus Sle Human

David A Isenberg, Bloombury Rheumatology Unit, Arthur Stanley House, London, UK It seems likely that the condition described by Hippocrates as herpes esthiomenos was a synonym for what is now known as systemic lupus erythematosus (SLE). In modern times this was first described by Cazenave and Clausit in 1852. In 1875 Hebra and Kaposi differentiated discoid lupus from the systemic form. By the beginning of the present century, Sir William Osier and others had comprehensively described many of...

Function

The B7 CD28 pathway is important for cellular and antibody responses to viral and microbial infections, cancer, graft rejection and the development of autoimmunity. During antigen presentation, B7 bound to CD28 or CTLA4 coassociates on the cell surface with MHC-peptide bound to TCR in the activation cap between T cell and antigen-presenting cell (APC) but engages a distinct signaling pathway. For B7-1, this colocalization depends on the short but highly positively charged cytoplasmic tail which...

Graves ophthalmopathy

Clinically, the changes occurring in the eyes of patients with Graves' ophthalmopathy (GO) arc, when overt, easily recognized and well described. In a significant number of patients the changes are more subtle, not detectable clinically or only demonstrable with highly specialized investigations such as computerized tomography of the orbits. As a result the true frequency of GO and the frequency of its association with AITD remains controversial. Is it a distinct organ-specific autoimmune...

The Ychromosome accelerator of autoimmunity

In contrast to the female predilection for lupus found in humans and most susceptible mouse strains, male BXSB mice develop a much more accelerated and severe disease than females. This striking sexual dimorphism is not hormonally-mediated, but results from a Y-chromosome autoimmune-accelerating (Yaa) gene that has not yet been cloned. The genetic contribution of Yaa to lupus susceptibility has been shown to be additive and dependent on other background genes. Non-autoimmune strains remain...

Autoantibodies

There is a spectrum of autoantibody reactivities ranging from organ-specific to non-organ-specific autoantibodies. Organ-specific autoantibodies react to antigens of only one tissue, such as to thyroid tissue. Non-organ-specific autoantibodies react with antigens common to all tissues, such as to different nuclear antigens, and are often associated with more generalized disorders, such as systemic lupus erythematosus. There is also a small group of intermediate autoantibodies with specificity...

Principle of the test

The CF test is based on the ability of patient serum antibodies to form complement-activating immune complexes upon binding to their antigens. In immune complexes the complement component Clq binds to neighbouring Fc regions of antibody molecules with at least two of its six globular heads. In subsequent reactions some of the early complement components (Cls, C4, C2 and C3) are consumed in sequential proteolytic cleavages. The antibody assay (Figure 1) is performed in two stages first, a...

Immunity can modulate behavior

The previous material has reviewed data indicating that behavioral triggers of the nervous system can regulate immunity. Several lines of evidence also indicate that components of an immune response can also signal the CNS. For example, many investigators have reported electrical changes in the hypothalamus following the administration of antigen. Others have reported that IL-1 stimulates release of corticotropin-releasing hormone from the hypothalamus into the hypophyseal portal circulation,...

Skin antigens

Patients with autoimmune skin disease, such as pemphigus vulgaris or bullous pemphigoid (BP) develop autoantibodies that bind to epidermal antigens. These antibodies are identified by IIF, using tissue sections of skin (e.g. foreskin) or other squamous epithelium (e.g. monkey esophagus) as tissue substrate. Patients with pemphigus vulgaris show serum autoantibodies to the intracellular area of the epidermis in 80-90 of cases. These antibodies are IgG, most of them bind complement, and they are...

Lupus susceptibility loci

A new avenue of inquiry for broadly defining the genetic defects of lupus is that of genome-wide searches using dense chromosomal maps derived from polymorphic microsatellite markers. Micro-satellites or simple-sequence length polymorphisms (SSLP) are repeats of usually dinucleotides that exhibit a high degree of polymorphism in the number of repeats at a given chromosomal site. Studies of the interspecific MRL-Ipr and Mus cas-taneous (CAST E1)F1 hybrid backcrossed to MRL-Ipr identified two...

Perspectives

Clearly, sex steroid hormones are capable of affecting the development and function of a variety of immune cells (Figure 1 and Table 1). With our increasing knowledge of immune system development and function, testing of hypotheses regarding the mechanisms of sex steroid actions should be increasingly fruitful. Understanding the etiology of these differences may help in the development of therapies for a variety of conditions where the immune system's actions are critical, such as in...

Membranedamaging toxins

Proteins, lipids and sterols are all known to be involved as targets for membrane-damaging toxins. Perhaps the best example of a toxin whose target is a membrane protein is the protease of L. pneumophila described earlier this enzyme also induces the hemorrhagic response seen in experimental infections. Since the membranes of endothelial and type 1 alveolar epithelial cells undergo pathological changes, it is reasonable to ascribe these to the proteolytic activity of this toxin. There are many...

Idiopathic autoimmune thrombocytopenic purpura ITP

A relatively common disorder in adults, ITP often complicates diseases associated with defective immune regulation (e.g. systemic lupus erythematosus, HIV infection, lymphoproliferative disorders, Hodgkin's disease). The onset of thrombocytopenia and bleeding is usually less abrupt than in drug-induced immune thrombocytopenia caused by-drugs other than heparin. In adults, ITP is usually chronic and seldom remits spontaneously. IgG and or IgM autoantibodies react with GPIb, GPIIb-IIIa, or other...

Chronic ITP

This is an autoimmune disorder which occurs most commonly in adults between the ages of 20 and 50 and is more common in women than in men (approximately 2 1). Unlike acute ITP, this disorder appears more insidiously, and extremely low platelet counts and severe mucosal bleeding are uncommon, although they may occur. Physical findings, as with acute ITP, reflect the degree of thrombocytopenia. An enlarged spleen or the presence of enlarged lymph nodes suggests another cause. A similar disorder,...

Characteristics of the organism and its antigens

The genus Chlamydia of the order Chlamydiales con sists of four species C. trachomatis, C. pneumoniae, C. psittaci and C. pecorum. C. trachomatis is comprised of three biovars, two of which are natural parasites of humans and the remaining biovar a pathogen solely for mice. The two human biovars are subdivided into 12 oculogenital serovars which are responsible for trachoma (serovars A, B, Ba and C) and genital infections (serovars D, E, F, G, H, I, J and K). Genital infections result in...

Cellular abnormalities

Transplantation experiments have documented that the genetic defects of lupus are associated with the lymphoid cell compartment. An increased number of activated memory phenotype T cells is observed in all lupus strains, B1 (Ly-1 ) cells are elevated in NZ mice, and there is a dramatic increase with age in BXSB of atypical monocytes. In Ipr and gld homozygous mice, there is a massive accumulation of a CD3+, CD48, B220+ T cell subset that appears to originate from the CD84 compartment. The T...

Ontogeny of immune function in ungulates

The first lymphoid organ to appear in the developing fetus is the thymus, which is the main component of mammalian primary lymphoid apparatus. In the fetal lamb, it initially consists of epithelial cells arising from pharyngeal pouches and is first observed macroscopically after about 35 days of gestation, at which time small lymphocytes begin to appear in the thymic tissue in the lamb, but this does not occur until around 60 days of gestation in the calf. Distinct differentiation into cortex...

Solubilization of membrane molecules

The most widely used detergents for membrane solubilization are the nonionic detergents Triton X-100 and NP40 that have almost identical properties. Typically, 1-10 X 107 cells are resuspended in 0.51 ml of the following buffer 50 mM Tris-HCl, 150 mM NaCl, 5 mM EDTA, 10 mM iodoacetamide, pH 8, containing either 0.5-1 Triton X-100 or NP40 and the following protease inhibitors leupep-tin, antipain, chymostatin, pepstatin (all 1 xg ml1) and 0.1 mM (AEBSF), and lysed at 0 C for 30 min. Insoluble...

Major histocompatibility complex MHC genes

Although lupus susceptibility is not restricted to a single MHC haplotype (Table 1), the major contribution of certain MHC alleles to lupus susceptibility has been clearly demonstrated. In BXSB mice there is a dominant role for H-2 while for NZ mice, heterozygosity of the MHC (H-2d z) appears to confer higher susceptibility. Yet, H-2d z heterozygosity is not the only factor contributing to accelerated autoimmunity in the F1 hybrid, as crosses of NZB with SWR (H-2q) or BXSB (H-2b) also develop a...

Eosinophils

Although eosinophils are usually considered as major contributors to host defenses against helminths, they resemble neutrophils in possessing chemotactic, phagocytic and microbicidal activity. Eosinophils kill bacteria and fungi by oxidative and nonoxidative mechanisms, although the composition of their molecular armamentarium differs from that of neutrophils. For example, instead of myeloperoxidase, which catalyzes the generation of hypochlorous acid and chloramines in neutrophils, eosinophils...

Laboratory diagnosis

Acute hepatitis A is not distinguishable from other forms of viral hepatitis on clinical grounds, although the diagnosis may be inferred in a patient with typical symptoms and the appropriate epidemiologic clues. Liver function tests, especially serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are sensitive measures of parenchymal liver damage, but are not specific for hepatitis A. The diagnosis of acute hepatitis A is most commonly confirmed by detection of...

Immunogenetics and the cytokine system

The association with different HLA types and disease progression has been reported in most cohorts studied, although only a few of the associations stand up to multicenter analysis. One of the most striking associations is the association with HLA-B27 and nonprogressors and in Caucasian populations the association of HLA-A1, B8, DR3 with more rapid progression to disease. The latter haplotype is also associated with enhanced baseline immune activation that in turn is associated with other...

Concluding remarks

It is the current view that autoantigens themselves drive the autoimmune response against them. In that view, nucleosomes are to be considered the relevant autoantigen for the genesis of antibodies to nucleosomes, histones and DNA. Indeed, it would not be expected that DNA occurs freely in the circulation or the organs of the immune system, since in the nucleus of the cell it is so tightly bound to the core histones. Evidence implicating the role of nucleosomes as the driving antigen has been...

Immunologic studies

The definitive diagnosis of endocarditis is dependent on the demonstration of vegetations on a heart valve at surgery or necropsy, or a peripheral embolus. Recently this has been augmented by a secondary set of clinical criteria. This consists of major criteria (positive echocardiogram and typical blood culture) and minor criteria (predisposition, fever, vascular phenomena, hematological phenomena, suggestive echocardiogram and suggestive microbiology). In addition to this there is increasing...

Reproductive Tract Infections

Morris D Cooper, Department of Medical Microbiology and Immunology, Southern Illinois University, School of Medicine, Springfield, Illinois, USA Nancy M Khardori, Department of Internal Medicine, Southern Illinois University, School of Medicine, Springfield, Illinois, USA The reproductive tracts of the male and female are anatomically distinct and present different sites for microbial colonization and pathogenesis. Primary infections of the reproductive tract are preceded by colonization of the...

Preliminary separation steps

At this stage, the method of extraction must be selected. Unless dealing with a secreted protein in cell culture, any extraction from a biological source will require mechanical disruption of cells. This leads to dispersion and dilution of cell contents resulting in release of proteolytic enzymes and general acidification. Appropriate buffer solutions can be used to guard against rapid acidification and addition of sucrose or maltose may help to stabilize lysosomal membranes and hence reduce...

Selected nutrient deficiencies

Clinical malnutrition is usually a complex syndrome of multiple nutrient deficiencies. However, observations in laboratory animals deprived of one dietary element and findings in rare patients with a single nutrient deficiency have confirmed the crucial role of several vitamins and trace elements in immunocom-petence. Deficiencies of pyridoxin, folic acid, vitamin A, vitamin C and vitamin E result in impaired cell-mediated immunity and reduced antibody responses. Vitamin B6 deficiency results...

APS type II

This is usually defined as the occurrence of two or more of the major components listed in Table 1 some would widen this to encompass various other features such as pernicious anemia, whereas others would limit the syndrome to those patients who have Addison's disease with thyroid autoimmune disease (Graves' disease or autoimmune hypothyroidism) and or type I diabetes mellitus. The clinical features of the individual components do not differ from the isolated disorders in their severity or age...

Immunological activities of transfer factors

A major concern in transfer factor research is how molecules with molecular weights of 4.9-5.4 kDa can transfer antigen-specific immune responses. The mechanism of this specificity has not been defined, but the evidence for specificity is so strong that it must be considered in formulation of models for transfer factor activity. For example, Maurer prepared lysates of leukocytes from human donors who had received ethylene oxide-treated human serum. These lysates would transfer delayed-type...

Clinical applications

The test is most commonly used to investigate suspected immunodeficiency in patients with unusual susceptibility to certain infectious diseases. Patients with severe immune deficiencies such as severe combined immunodeficiency (SCID) have little or no lymphocyte transformation responses to mitogens or antigens, even when they have normal numbers of lymphocytes in their blood. In other disorders, such as chronic mucocutaneous candidiasis, responses to mitogens may be normal, but the patients'...

Natural history of SLE

The prevalence of lupus varies according to ethnic group. Amongst black females it is approximately 1 in 250, amongst Chinese approximately 1 in 1000, amongst Caucasian about 1 in 4000. The female-to-male ratio in lupus is approximately 9 1 though some studies have indicated that there are families in which the disease occurs in mainly males and is transmitted through the fathers. Pregnancy for the lupus patient entails far more danger for the offspring than the mother. Generally speaking...

Immune responses of the host

Candida species are found commonly in the environment, and can be recovered from the soil. They are normal flora in the human gastrointestinal tract, and can often be found at other mucosal sites and on diseased skin. The initial host defenses are the nonspecific barriers including intact skin and mucosal epithelium, as well as the indigenous bacterial flora that competes for binding sites. Breakdown of these barrier functions, (e.g. from burns or indwelling intravascular devices) allows for...

Immunodeficiency Primary

A David B Webster, Department of Clinical Immunology, MRC Immunodeficiency Research Group, Royal Free Hospital School of Medicine, London, UK The first patient with hypogammaglobulinemia was diagnosed by Bruton in 1952 soon after the introduction of serum protein electrophoresis. At about the same time, severe combined immunodeficiency (SCID) was described in Switzerland and has subsequently been subclassified into a number of different disorders. In 1965, DiGeorge showed that the thymus was...

Vaccination and immunotherapy

The development of vaccines against the important systemic fungal infections is under intense investigation. A vaccine consisting of formaldehyde-killed spherules of C. immitis was protective in a mouse model of coccidioidomycosis, but no efficacy was demonstrated in a large trial of susceptible persons in the endemic area. Local reactions limited the dose that could be given. Immunization with subcellular fractions or purified antigens is likely to be better tolerated and suitable antigens are...

Preface

This encyclopedia provides the largest integrated reference source of immunological knowledge that is available. In the six years since the first edition of the Encyclopedia of Immunology was published, there have been astounding advances in many areas of the subject. The second edition of the encyclopedia seeks to encompass these advances and to provide a more up-to-date coverage of the subject as a whole than is now provided by the original text. The large number of the topics covered will be...

ALS as an immunosuppressive agent

ALS is used, often in combination with other immunosuppressive agents, to avoid allograft rejection. In a quadruple therapy protocol it is used with azathioprine, steroids and cyclosporine. ALS is used both as a preventive immunosuppressant, for initial treatment of rejections, and to treat steroid-resistant rejection. The mechanism of action is not fully clarified, but depletion of circulating lymphocytes does occur. This may result from either cytotoxic mechanisms or opsonization. The widest...

Tissue injury by neutrophils

The neutrophil contains a formidable arsenal of proteinases, lysozyme and oxygen radical-forming enzymes in its granules, usually employed to kill microorganisms ingested by the neutrophil. Occasionally, however, these injurious products may be released to the extracellular space and cause tissue damage, for example if the perceived foreign body is too large for ingestion. In addition, antiproteinases normally present in the interstitial fluids can be inactivated by neutrophil-derived oxygen...

Pathogenetic implications

Bence Jones proteins play a direct role in myeloma-associated kidney disease and their measurement is of important prognostic significance. They are also involved in visceral diseases featuring tissue deposition of LC-related material. Combined study of serum and urine by sensitive methods reveals evidence of BJP in almost all cases of AL (amyloid light chain) amyloidosis. In LC deposition disease, tissue deposits of monoclonal LC (and of monoclonal heavy chains in some patients) correlate with...

Hematologic malignancy

Hematologic malignancies are typically associated with profound defects in one or more aspects of host defense, with the result that infection is a major cause of morbidity and mortality in this group of patients. Neutropenia and impaired phagocytic capacity due to bone marrow failure is an intrinsic feature of the acute leukemias but can occur from marrow infiltration in the later stages of other malignancies, and is an almost inevitable if temporary side-effect of curative cytotoxic...

Synthesis and distribution

IgA is found in species which emerged after the appearance of amphibia, although evidence has been presented that IgA-like molecules may exist in fish. In most higher vertebrates, the majority of IgA is synthesized by gastrointestinal lymphoid tissue, with smaller amounts synthesized at other mucosal sites such as the respiratory tract, salivary glands and reproductive tract. During lactation, mammary tissue contains substantial numbers of IgA-producing cells. The majority of these arc thought...

Acquired immune deficiency syndrome AIDS

Human immunodeficiency virus (HIV) infects helper (CD4+) lymphocytes and cells of the monocyte macrophage series. This produces a slowly progressive, profound immune defect which may be further exacerbated by opportunistic infection with, for example, CMV, EBV and other viruses. Several months or years may intervene between initial HIV infection and the development of opportunistic infection. A febrile prodrome associated with general malaise, intermittent diarrhea, and severe weight loss may...

Definition

Allergy was originally defined in 1906 by Clemens von Pirquet as 'altered reactivity' to denote the different reaction which occurs on second exposure to an antigen, due to the formation of antibodies, when compared to the first exposure. Used in this way the term covered all imune reactions however, its use has since become restricted to certain hypersensitivity reactions. The term atopy (from the Greek 'out of place') was introduced by Coca and Cooke in 1923. They had observed that certain...

Immunotherapy of autoimmune bullous dermatoses

Pemphigus and pemphigoid are primarily treated with high doses of oral prednisone, up to 200 mg per day. In limited cases, topical steroids may be given a try. In pemphigoid, a combination of tetracyclines and niacinamide has been shown to have good results and this combination might be given a try before deciding to give systemic steroids. Azathio-prine is given as a corticosteroid-sparing drug in prednisone-treated patients. Other systemic drugs used are cyclophosphamide and cyclosporine. The...

Clinical effects

The clinical effects of type I hypersensitivity depend upon the site of the reaction involvement of the nose and or lungs results in rhinitis and or asthma skin involvement causes urticaria. Atopic eczema involves IgE-mediated allergy, although the histology resembles a type IV hypersensitivity reaction. It is possible that an initial type I mechanism causes increased vascular permeability, allowing the influx of lymphocytes. Type I reactions to food can cause immediate reactions involving...

Triggering immune reaction against cancers

Antigen presentation, cytokine-mediated cell activation and receptor-ligand interactions are interactive pathways able to induce normal immune responses. Failure of the immune system to direct a therapeutically efficient immune reaction against tumor cells can be due to insufficient effector cell activation. Experimentation and clinical trials based on these concepts, alone or in combination, have been developed to induce antitumor responses by manipulating either tumor or effector cells (Table...

Cancer susceptibility

During the shortened lifetimes of AT homozygotes, 38 develop a malignancy, usually lymphoid. This represents a 61-fold and 184-fold increase in Euro-American and Afro-American patients, respectively. About half of the malignancies observed are lymphomas, usually of the B cell type. Leukemias account for another quarter of the malignancies. These are usually T cell leukemias. Young AT patients develop a less aggressive T cell leukemia than older patients, who develop a prolymphocyte-leukemia...

Insects

Allergic reactions to the venoms of social Hymenop-tera are relatively common. Estimates of the prevalence of stinging insect allergy by history range from 1 to 10 of the population. A random screen of industrial employees in the mid-Atlantic USA found that 26 exhibited evidence of sensitization by being either skin test or radioallergosorbent test (RAST or specific immunoglobulin E (IgE) antibody measurement) positive. Highly exposed populations have been found with over half of the subjects...

Pathological alterations of the classical pathway

The functioning of the classical pathway is disrupted in many circumstances. These include genetic deficiencies of single components complete deficiencies of Clq, Clr, Cls, C4, C2, C3, factors H and I have been reported. These are associated with susceptibility to infection and or inappropriate deposition of immune complexes. Low concentrations of MBL are associated with poor opsonization of yeast and some bacteria, and with recurrent infection in infants. Diminished synthesis of Cl-inh, or...

Antigenic variation in lentiviruses

Antigenic variation in an individual host occurs with animal lentiviruses. The first report of antigenic drift was in equine infectious anemia virus (EIAV). Horses infected with EIAV develop sequential episodes of acute hemolytic crises during persistent infections. Sera taken at various times from an infected animal were able to neutralize isolates from previous clinical episodes, but failed to neutralize subsequent viral isolates. Visna virus in sheep also causes persistent infection,...

Atopic dermatitis

Atopic eczema, also known as atopic dermatitis, is a very common entity. One out of every 20 children will have an episode of atopic dermatitis during one or more periods of their lives. The disease is part of a syndrome known as atopy. It is genetically determined but the precise gene(s) responsible have not yet been identified. Other diseases that form part of atopy are extrinsic allergic asthma, rhinitis allergica, conjunctivitis allergica and certain forms of allergic food reactions....

Mercuryinduced immune systemrelated disease in humans

Allergic contact dermatitis is a well-established complication of mercury exposure. It may result from handling of metallic mercury and or topical administration of mercury-containing agents. Allergic contact dermatitis has also been described in persons exposed to mercury-containing antiseptic solutions, cosmetics or eye drops, or following inhalation of mercury vapour. Allergic contact dermatitis to mercury appears to be one of several causes of the so-called baboon syndrome. Low amounts of...

Diagnosis and mechanisms

The major foods responsible for allergic reactions may be related to age as well as specific ethnic and local practices. Food allergens in infants are usually limited to cow's milk, eggs, fish, cereal and soya. In older children the diet is more or less the same as that of their parents it therefore includes a larger variety of potential allergens. Some of the major criteria used for the diagnosis of food allergy are presented in Table 1. One of the major steps toward a correct diagnosis is the...

Structure specificity and cellular distribution of complement receptors

CR1 (CD35) binds to C3b, and with lower affinity to C4b and iC3b. Proteolysis of iC3b into C3dg destroys CR1 activity. Several cell types express CR1, including erythrocytes, phagocytic cells, lymphocytes (B cells and some T cells), kidney podocytes and peripheral nerves. CR1 along with CR3, CR4 and immunoglobulin G (IgG) Fc receptors are the major opsonin receptors on phagocytic cells. The CR1 of erythrocytes has two important functions in the clearance of circulating immune complexes. First,...

Glucocorticoids

Patients with IgG-induced immune hemolytic anemia usually respond to glucocorticoid therapy in dosages equivalent to 40-120 mg of prednisone a day. Glucocorticoids work in IgG-induced hemolytic anemia by three primary mechanisms. First, they decrease the production of the abnormal IgG antibody. This is the most common effect and produces a gradual increase in hemoglobin within 2-6 weeks. Second, glucocorticoids have in several cases been demonstrated to cause the elution of IgG antibody from...

Peripheral nerve disease

Experimental autoimmune encephalomyelitis is a demyelinating disease of the CNS. In 1955, Waks-man and Adams described an autoimmune disease of the peripheral nervous system, experimental autoimmune neuritis (EAN), which they induced in rabbits immunized with sciatic nerve tissue in adjuvant EAN serves as a model for Guillain-Barre syndrome. Animals with EAN develop cellular immunity and antibodies to the P2 protein, an autoantigcn found in peripheral nerve myelin. P2 is a basic protein...

Heterogeneity of CAH

It was realized in the early 1970s that 'chronic active hepatitis' was a generic term for a liver disease with a variable expression and etiology. The hepatitis B surface antigen (HBsAg) had been identified as a marker of infection with hepatitis B virus (HBV), so that some cases of CAH could be characterized as HBV-associated CAH, in addition to autoimmunity and other causes. Several categories of CAH can now be listed, as follows 1) The archetypic CAH described in the 1950s as lupoid...

Type I hypersensitivity

The central mechanism of atopic allergy is type I hypersensitivity (Figure 1). Mucosal contact with allergen results in uptake by an antigen-presenting cell (APC) and presentation in the form of an allergenic peptide held in the groove of the major histocompatibility complex (MHC) class II molecule to a helper T lymphocyte. This then provides help for a previously committed B cell, which is capable of recognizing the antigen, to make IgE antibody. Factors determining IgE rather than IgG...

IgE Antibodies against nonhuman antigens

In patients who are allergic to an allergen, an allergic reaction occurs if the donor plasma contains the allergen. This may particularly occur if it concerns food allergens, which may be present in the donor plasma after consumption of the food involved. The patient develops urticaria. The reactions can be prevented, in the case of red cell concentrates, by washing the cells three times. Very rarely a similar reaction is induced by donor IgE antibodies against an allergen which at the time of...

Expression and biologic activity of recombinant allergens

Traditional methods of allergy diagnosis and treatment have relied on the use of heterogeneous allergen extracts. The problems with these extracts are that the absolute potency is difficult to define and some patients give adverse reactions when the extracts are injected (during immunotherapy), which can be life threatening. While there has been significant progress in the standardization of allergen extracts the use of purified recombinant allergens expressed in bacteria, yeast or insect cells...

Drugs Allergy To

Timothy J Sullivan, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA Pharmacologically active agents administered to humans for diagnostic or therapeutic purposes can cause a wide range of immunologically mediated diseases. Drugs can act as immunogens that induce immune responses and then elicit immunopathologic reactions. In addition, a variety of agents used in human medicine can activate immune effector systems through pharmacologic rather than immunologic...

Physiological role of CSF

Physiologically, the CSFs can be regarded as part of a larger family of peptide regulatory factors or cytokines that play a major role in regulating the body's response to infection or injury. A general characteristic of the CSFs is that they stimulate not only the growth of progenitor cells leading to production of various differentiated progeny, but also the effector functions of the mature differentiated cells. Thus GM-CSF can prime for a respiratory burst in neutrophils, and GM-CSF and IL-3...

Source function and chemical nature of eosinophil chemotactic factors

There are two main sources of eosinophil chemotactic factors 1) blood and tissue fluid and 2) a diverse number of cells. The main eosinophil chemotactic factors in the fluid compartment are the complement-derived anaphylatoxins C3a and C5a, and to a lesser extent the latter's cleavage product C5a-desarg (Table 1). Whereas both are highly potent chemota.x-ins for eosinophils, C5a also activates several other mononuclear cell types. Most eosinophil chemotactic factors derive from resident tissue...

Idiotype Network

Constantin A Bona, Department of Microbiology, Mount Sinai Medical School, New York, USA Copyright 1998 Elsevier Ltd. All Rights Reserved. The idiotype network theory formulated by Jerne views the immune system as being interconnected by idiotopes which are the antigenic determinants of variable regions of a lymphocytic receptor. Each receptor has several idiotopes which are collectively designated as its idiotype. The immune system is composed of lymphocytic clones that are able to recognize...

Uag

Figure 1 The genetic organization of hepatitis B virus. The HBV virion contains a circular, partially double-stranded DNA genome which contains four overlapping open reading frames. Gene C encodes the two nucleocapsid antigens, HBcAg and HBeAg, gene S encodes the small, middle and large surface antigen proteins, region P the viral polymerase and region X the X protein. The largest open reading frame encodes for a bifunctional protein which has DNA polymerase and reverse transcriptase functions....

Further reading

Estey EH (1994) Use of colony-stimulating factors in the treatment of acute myeloid leukemia. Blood 83 2015-2019. Freifeld A and Pizzo P (1995) Colony-stimulating factors and neutropenia intersection of data and clinical relevance. Journal of the National Cancer Institute 87 781-782. Hamilton JA (1993) Colony stimulating factors, cytokines and monocyte-macrophages - some controversies. Immunology Today 14 18-24. Metcalf D (1995) The granulocyte-macrophage regulators reappraisal by gene...

Infections characterized by an eosinophilic IgEmediated immunologic response

Certain skin infections provoke an immunologic response in which eosinophils, mast cells, basophils and IgE antibody-mediated reactions play prominent roles. Such responses are often orchestrated by activated T cells and the production of interleukins such as IL-4 and IL-5. Involvement of the skin by the microfilarial stage of Onchocerca volvulus results in such a response. Onchocerciasis is caused by the filarial nematode O. volvulus. Infective larval stages of the worm are inoculated into...

Immune response of the host

Sera from animals or humans with a history of infection generally react with papillomavirus capsid proteins. Antibodies to the E7 protein of HPV16 and HPV18 are frequently found in sera of patients with cervical cancer. Similarly, antibody titers against the E2, E6 and E7 proteins have been detected in patients' sera. Infection with the common papillomaviruses of the skin and mucosa often results in a chronic infection. This chronic infection occurs in the immunocompetent host, suggesting that...

Parvovirus B19 biology

B19 belongs to the Parvoviridae family, which has been divided into the subfamilies of insect parvoviruses (Densovirinae) and vertebrate parvoviruses (Parvovirinae). The Parvovirinae are further divided into three genera, of which one (Dependovirus) requires coinfection of target cells with a herpes virus, whereas the other two (Parvovirus and Erytbrovirus) replicate autonomously. B19 and the recently discovered simian parvovirus (SPV) belong to the newly formed genus Erytbrovirus. B19 is a...

Editorial Advisory Board

Basten, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No. 6, Newtown NSW2042, Australia C. A. Bona, Department of Microbiology, Mount Sinai Medical School, 1 Gustave Levy Place, New York, NY 10029-6574, USA J. Brostoff, Centre for Allergy Research, Department of Immunology, University College London Medical School, Windeyer Building, 46 Cleveland Street, London W1P 6DB, UK B. Cinader, Department of Immunology, Medical Sciences Building, University of Toronto, 1 King's...

Cytokines and vascular endothelium

Endothelial cells and leukocytes interact closely in the activation and expression of immunity as well as in inflammatory reactions and hemostasis. Cytokines are important mediators of this interaction, endothelial cells being both a source and target for the action of polypeptide mediators. Effects of cytokines on endothelial cells Cytokines produced by activated lymphoid cells and mononuclear phagocytes elicit a complex spectrum of responses in vascular cells. These can be grouped into...

Historical background

In 1952 Colonel Ogden C Bruton reported the case of an 8-year-old boy with a 4 year history of recurrent bacterial sepsis, osteomyelitis and otitis. This child failed to make antibodies to pneumococcus after repeated antigenic challenge. In a seminal observation, Bruton noted that the patient's serum lacked the gamma globulin fraction by electrophor-etic analysis but was otherwise normal. This was the first case in which an abnormal result in a laboratory study explained the clinical problems...

Nomenclature and general properties

Atopic individuals become sensitized to allergens through exposure by inhalation (e.g. pollen grains, mite feces, animal danders, cockroach secretions, and fungal spores), by ingestion (e.g. milk, egg, peanut, fish), and by injection (e.g. insect venoms and parenterally administered drugs, such as penicillin). In general use, the term allergen can refer to these sources, to aqueous extracts prepared from the source materials, or to highly purified or cloned allergen proteins. The systematic...

Neutrophil cytoplasmic antigens

Antineutrophil cytoplasmic autoantibodies (ANCAs) have recently become an important diagnostic tool for vasculitis associated with Wegener's granuloma tosis and certain other microscopic vasculitis and glomerulonephritis disorders. The antibodies are detected primarily by IIF on isolated human neutrophils as substrate. Differences in fixation of the cells can separate the antibodies into two distinct groups with different specificities C-ANCA and P-ANCA. Ethanol fixation causes a redistribution...

Common Variable Immunodeficiency

Thomas A Selvaggi, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Bethesda, Maryland, USA Michael C Sneller, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Common variable immunodeficiency (CVI) is a heterogeneous syndrome characterized by hypogammaglobulinemia and recurrent bacterial infections. This rare syndrome has an...

Allergic contact dermatitis

An important characteristic of skin is that it is continuously exposed to environmental influences, such as ultraviolet irradiation. Numerous microorganisms and their degradation products, organic and inorganic chemicals, and natural and artificial compounds are continuously challenging the skin's epidermal barrier. This barrier is formed by the horny layer, which is composed of corneocytes (keratinocytes that entered a programmed cell death pathway leading to cellular structures filled with...

Mediators and nasal allergy

Mediator release after nasal airway challenge with allergen has now been extensively investigated. Nasal lavage for the recovery of secretions on the surface of the nasal mucosa has made it possible to identify a postallergen challenge increase in a vast number of putative mediators of inflammation in humans. As well as experimental provocation tests, the inflammatory response of the nasal mucosa to natural exposure to pollen can also be measured. Much can be learned about the immediate (early)...

Phospholipid antigens

Antiphospholipid autoantibodies are a heterogeneous group of antibodies with specificity to a phospholipid-protein complex. The protein associated with cardiolipin has been identified as a -glycoprotein ( 32-GPI). Some investigators suggest that this is the relevant autoantigen in patients with antiphospholipid syndrome, although the relative importance of these two molecules has not yet been fully clarified. The most sensitive test used is an ELISA using cardiolipin or other phospholipids to...

Antigen uptake by mucosal surfaces

The structure of mucosal surfaces (epithelium with tight junctions and a mucous layer) itself is an important determinant of antigen exclusion. Macro-molecules are shown to transgress this barrier by endocytosis. Granulocytes, macrophages and plasma cells in the lamina propria interact with these absorbed antigens, thus forming a secondary barrier of defense against penetration of antigens into the circulation. Certain diseases or altered states (e.g. malnutrition, vitamin A deficiency,...

Clinical reactions to drugs

Immune responses to drugs are necessary but not sufficient for clinical allergic reactions to drugs. If the fluid phase has an excess of univalent haptenated carriers over multivalent carriers, many immunopathologic reactions will not occur. Cross-linking of IgF and activation of mast cells will not occur. Immune complexes cannot form in univalent hapten excess. Direct cytotoxic reactions are inhibited by fluid phase determinants. The affinity and isorype arrays of the immunoglobulins expressed...

Inflammatory Bowel Disease

Robert D Fusunyan and Ian R Sanderson, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts and Lahey Hitchcock Clinic, Burlington, Massachusetts, USA Inflammatory bowel disease (IBD) consists of two major illnesses, ulcerative colitis and Crohn's disease, which are chronic disorders of the intestine of unknown origin. Both diseases exhibit chronic inflammatory changes consisting of an intense infiltration of macrophages and...

Transgenic mice

Honjo and his colleagues generated transgenic mice expressing one of the pathogenic IgM monoclonal antibodies derived from NZB mice. In these mice conventional (B-2) B cells were deleted, presumably after contact with RBCs, but normal numbers of CD5 B-l cells were present in the peritoneal cavity and lamina propria. About 50 of these mice developed AIHA in a conventional environment but not if maintained in isolators. Oral administration of LPS induced AIHA in asymptomatic anti-RBC transgenic...

Mediators of the hypothalamicpituitaryadrenal axis

Hypothalamic dysfunction, hypophysectomy (removal of the pituitary gland) and adrenalectomy, separately or in combination, have dramatic and long-lasting effects on circulating immunocompetent cells. The absence of the pituitary gland eliminates the major source of various neuroendocrine hormones and neuropeptides, including luteinizing hormone, follicle-stimulating hormone, ACTH, prolactin, and growth hormone. The effect of hypophysectomy on the immune response is to alter the numbers of...

Diagnosis

Autoimmune diseases are usually diagnosed according to the functional deficits that ensue in affected organs, rather than by their immunological features per se. This applies to autoimmune disease affecting the thyroid gland, adrenal gland, pancreatic islets, stomach, liver, kidney, muscles, neural transmitters, etc. However, testing for the disease-relevant autoantibody will in many instances provide specific and decisive diagnostic information, exemplified by testing for the antiglobulin...

The question of efficacy

In insect venom immunotherapy, protection is achieved in well over 90 of subjects following a short (usually several day) course of injections. Efficacy is commonly tested by deliberate administration of an insect sting challenge in the presence of a physician, yielding clear-cut evidence of success or failure. In contrast, the efficacy of immunotherapy for inhalant allergens, used in therapy of allergic rhinitis or allergic asthma, remains controversial. Proponents argue that allergen...

Etiology

The cause(s) of autoimmune Addisons disease is(are) still unknown. Expression of MHC class 11 antigens, suggested as a key event in the initiation and or maintenance of organ-specific autoimmunity, occurs in normal adrenals and, therefore, is unlikely to be the primary etiologic event of Addisons disease. Defects in HLA-DQ(3 chain, found in IDDM, have not been reported in patients with Addisons disease. On the other hand, a deficiency of T suppressor cell activity was noted by some authors. To...

Immunotherapy Of Allergic Diseases

Kent T HayGlass, Department of Immunology, University of Manitoba, Winnipeg, Canada Allergen immunotherapy represents the dominant immunologic, as opposed to environmental or pharmacologic, approach to management of allergic diseases such as allergic rhinitis, conjunctivitis and asthma. It was developed empirically, coincident with the modern-day discovery of allergy by Portier, Richer and von Pirquet. In essence, it involves identification of the allergen(s) to which a patient exhibits...

Special considerations Occupational asthma

Approximately 2 of all asthma is related to occupational exposures. A large and growing list of agents may precipitate this syndrome, including vegetable materials, chemicals, animal materials, metals and pharmaceuticals. While the high molecular weight compounds are complete antigens that elicit IgE synthesis, many of the low molecular weight compounds are haptens, creating a complete antigen only when bound to carrier proteins. There is often a latency period between the onset of exposure and...

Asthma

David M Essayan and Lawrence M Lichtenstein, Division of Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Asthma is a disease of the lungs affecting both children and adults and characterized by 1) airway obstruction that is partially or completely reversible, 2) airway inflammation, and 3) airway hyperres-ponsiveness. A persistent rise in disease prevalence, hospitalizations due to disease exacerbation, and disease mortality...

Biological effects in vivo

Transgenic technology has provided additional information regarding the biology of GM-CSF. Over-expression of GM-CSF in transgenic mice led to the accumulation of macrophages in the eye, resulting in blindness, and infiltration of macrophages into striated muscle. This demonstrated that high concentrations of GM-CSF during development may have pathologic consequences and sounded some warnings for clinical trials. Targeted disruption of the GM-CSF gene has resulted in homozygous mice with no...

Immunosuppressive agents

Several chemotherapeutic agents with known immunosuppressive effects have been used to treat immune hemolytic anemia. The drugs most commonly used include the thiopurines (6-mercaptopur-ine, azathioprine and thioguanine) and alkylating agents (cyclophosphamide and chlorambucil). Immunosuppressive therapy may be effective for treating patients with IgG-induced immune hemolytic anemia when patients are refractory to steroids or splenectomy. Immunosuppressive agents work by decreasing the...

Host resistance to UTI

The urine flow is a major host defense mechanism as shown by the drastically increased frequency of UTI in patients with catheters or other mechanical defects. Individuals prone to UTI have an increased tendency to carry uropathogenic E. coli in the intestinal flora and introital area. Epithelial cells from these sites have a higher density of receptors than cells from healthy controls. The establishment of bacteria in the urinary tract is also thought to be influenced by the host expression of...

Animal models of inflammation induced by gene disruption

Dominant negative N-cadherin mutants Cadherins are transraembranous glycoproteins that mediate cell adhesion. The cytoplasmic domain of N-cadherin includes a 3-catenin which, in turn, binds an a-catenin. The catenin-cadherin complexes regulate a variety of cell functions, including proliferation, polarity and migration. Disruptions of these interactions result in the development of IBD that closely resembles Crohn's disease. Chimeric mice, generated from normal blastocysts and genetically...

Immunoglobulin synthesis and secretion

Intestinal mononuclear cells from healthy mucosa normally secrete large amounts of IgA. In IBD, IgG cells are increased relative to IgA cells and are present in deeper tissue layers. The mucosal immune system exhibits a markedly heightened IgG immune response because of defective or altered immuno-regulation. In IBD, intestinal and peripheral blood mononuclear cells secrete increased immunoglobulin, particularly of the IgG isotype. The greatest increase in spontaneous IgG secretion is seen in...

Preparadigmatic immunology

Protoimmunology from the ancients to the Enlightenment The scourges of infectious diseases have declined steadily and dramatically during the last century. During this period, modern immunology had its beginnings and immunologists, not surprisingly, tend to see a causal relation between these events. But the discipline of public health was developed before immunology and has almost certainly played a larger role in the control of infectious disease and the elevation of the lot of humankind. It...

Hladr3

Idiopathic adrenal insufficiency h hypoparathyroidism + chronic mucocutaneous candidiasis + gonadal failure Most commonly in childhood Males and females Unknown (very rare) No HLA-DR association P450 side-chain cleavage Idioopathic adrenal insufficiency + insulin-dependent diabetes mellitus + autoimmune thyroiditis All ages, but more commonly in patients HLA-DR3 and or DR4 Steroid 21 -hydroxylase P450 Figure 1 (A) Adrenal gland from patient with Addisons disease, showing atrophy of the cortex...

Chicken strains and genetic variability

Over a dozen highly inbred chicken strains, representing at least 10 of the approximately 30 characterized different MHC (B locus) haplotypes are available. Skin grafts between birds of the same inbred strain are permanently accepted, with the exception of female to male grafts, which are slowly rejected, hens being the heterogametic sex. MHC-congenic and recombinant haplotypes are available on some of the highly inbred backgrounds. Four p, chain, 10 7 chain and two light chain Ig allotypic...

Complement pathway activation

Activation of complement results in the generation of proinflammatory products which may ultimately lead to tissue destruction. Various studies have demonstrated the possible role of complement in tissue damage in ulcerative colitis. Monoclonal antibodies against a neoepitope exclusively expressed by activated C3b and the cytolytically active terminal complement complex have been used to identify potential complement-induced damage in tissue sections from inflamed IBD intestine. Eighty per cent...

Other endocrine organs

Autoimmunity also develops against other endocrine organs such as the adrenal gland, pancreas islet cells, parathyroid, pituitary and ovary. The autoantibodies are much less prevalent than with thyroid disease but, if present, help in diagnosis. The reactivities, assays and primary associated disorders are summarized in Table 1. These autoantibodies share certain characteristics. Antibodies bind to antigens associated with the cytoplasm of cells, usually to unidentified antigens. The antibodies...

Antiphospholipid syndrome

Antiphospholipid syndrome (APS) is a disorder of recurrent arterial and or venous thrombosis and thrombocytopenia associated with the presence of antiphospholipid antibodies (aPL). Although scattered case reports existed, the term APS was first used in 1985 with tentative criteria being proposed in 1987. Approximately 50 of these patients are considered to have the primary APS (PAPS) and 50 secondary APS (SAPS). SAPS seems to be clinically indistinguishable from PAPS except for an association...

Etiology and pathogenesis

Urine is an excellent culture medium and contains sufficient nutrients to support bacterial growth to a density of 107CFUml '. Ideal conditions, of urine pH 4-7 and concentration of 300-800 mosmol kg are common. Bacteria most commonly enter via the urethra (ascending infection) or may enter via the bloodstream. Ascending infections, which account for the great majority of cystitis and pyelonephritis, are mainly due to organisms of the normal bowel flora - principally Escherichia coli (75 or...