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...

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...

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...

Characteristics of the organism and its antigens

Infections due to organisms in the genus Candida are relatively common, with a variety of different manifestations of disease in both humans and animals. These organisms all grow as yeast and most of the individual species also have filamentous forms, which are either pseudohyphae or true hyphae. There are over 150 species of Candida, but only 10 are significant pathogens for humans. These species include C. albicans, C. glabrata (formerly Torul-opsis glabrata), C. parapsilosis, C. krusei, C....

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...

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...

Evasive strategies by the organism

Adhesion is an important initial step in infection of epithelial or mucosal sites. In this regard, Candida organisms have been shown to express three types of adhesion molecules. After adhesion of the organisms, other potentially important virulence factors of Candida which may assist in promoting invasive disease include lytic enzymes, hyphal formation, and contact sensing. One lytic enzyme, an aspartyl proteinase, may assist penetration into the stratum corneum. Another enzyme, a keratinase,...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

Specificity and characterization of T cells

Since the generation of pathogenic anti-RBC autoantibodies is CD4 T lymphocyte dependent, it would be predicted that NZB mice harbor helper T cells responsive to RBC autoantigens. Splenic T cells from NZB mice, but not other H-2ci strains such as BALB c or DBA2 mice, do indeed proliferate in vitro in response to band 3. The majority of the responding cells express CD4 and the response is major histocompatibility complex class II restricted. Thus the T cells which help the production of the band...

Specific immunity Antibody

Although it is difficult to draw definite conclusions, for most of the mycoses there is little evidence to suggest that specific antibodies are critical to host defense. In marked contrast to patients with impaired cell-mediated immunity, those with hypogammaglobulinemia are not particularly predisposed to the development of invasive fungal infections. The principal role of antibody may be to enhance binding of fungi to phagocytic cells via Fc receptors. In the case of crytococcosis, specific...

Inheritance

Three pieces of evidence converge to suggest that there is a genetic predisposition to pernicious anemia the high prevalence of pernicious anemia in some racial groups, the high frequency of pernicious anemia in families within those racial groups, and the association of particular genetic markers among patients with pernicious anemia. Pernicious anemia is predominantly a disease of people of Northern European origin, it is rare among Southern Europeans, Asians, Latin-Americans, and African and...

Systemic sclerosis scleroderma and related disorders

Systemic sclerosis (SSc) is a diffuse connective tissue disease of unknown etiology which is characterized by fibrosis of skin and internal organs with associated autoantibodies and microvascular pathology. The peak ages of incidence are in the fifth and sixth decades of life, females, particularly women of child-bearing years, are affected more commonly than males. Related disorders include CREST syndrome, mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease...

Disorders associated with food allergens

The variety of intolerance reactions due to foods is great. In infancy and early childhood, cow's milk and soya are the major causes of allergic reactions, followed by cereals, eggs and fish. The age of onset is highly variable, from the first days of life (cow's milk) to the age of 2 years. In 90 of cases, clinical intolerance disappears after the age of 3 years. The most common clinical picture is of vomiting, diarrhea and abdominal pain, usually appearing within minutes, or at the most 1-2...

Apoptosis in immunity

In the immune system, apoptosis is used as a means to dispose of unwanted cells time and again. In many cases the CD95 molecule (Fas APO-1), a member of the TNF NGF receptor family, is used to transduce the death signal. Some of the situations where Phenotypic changes characteristic of apoptosis Figure 5 Molecular events in apoptosis. Members of the cas-pase (ICE CED-3) protease family are depicted as being at a point just below the convergence point for diverse proapoptotic stimuli. Activation...

Clinical presentation

Asthma may present acutely or as a chronic pulmonary disease. Symptoms of acute asthma include shortness of breath, chest tightness, wheezing and cough, often productive of clear or slightly colored sputum. When present, chest pain is usually musculoskeletal in origin. Audible wheezing may not be present in mild asthma, but may be elicited by forced expiratory maneuvers. Increased diurnal variations in pulmonary function are often associated with nocturnal exacerbations. Triggers for worsening...

Creactive Protein

Mark B Pepys, Immunological Medicine Unit, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK C-reactive protein (CRP) is a member of the pen-traxin family of plasma proteins, which are unrelated to other known proteins but which are themselves stably conserved in vertebrate evolution. There is even a homologous CRP-like protein which is a major constituent of the blood of the so-called horseshoe crab, the arachnid Limulus polyphemus. The other pentraxin...

Granulocyte and macrophage function

Peripheral blood granulocytes and monocytes isolated and radiolabeled with indium-11 1 in vitro and reinjected into patients, migrate to inflamed areas of the intestine. In one study, more than 90 of radiolabeled phagocytes accumulated rapidly in the inflamed intestine of 91 (20 of 22) of Crohn's disease patients. A further study on 15 patients with ulcerative colitis showed enhanced migration of similar cells into areas of inflamed bowel. The migration of leukocytes from the vascular lumen...

Adenoviruses as vectors for the delivery of foreign genes

Ads have been developed as vectors for the delivery of foreign antigens for immunization against other (non-Ad) infectious agents and for gene therapy. Ads are good vectors for the delivery of foreign DNA in that viral replication is not dependent upon host cell replication, they can be molecularly engineered to enter host cells and express foreign proteins without infectious viral progeny, and they are extremely safe immunogens that have already been administered to many people. For gene...

Toxins that act on noncellularextracellular elements

Pseudomonas aeruginosa elastase and one (only) of at least six proteases of Legionella pneumophila both induce fibrinopurulent exudation (influx of fibroblasts and leukocytes) in the rat lung (a model for P. aeruginosa-induced pneumonia in human cystic fibrosis) and the guinea pig lung (a model for legionnaires' disease) respectively. These characteristic pathological features almost certainly arise from the release of oligopeptides (from extracellular matrix substances) which are chemotactic...

The HIV vaccine challenge

The principle of vaccination is straightforward the inoculation of a safe antigen to induce an immune response against the etiological agent of an infectious disease and in doing so confer protection to subsequent infection. Successful vaccines currently available against virus-induced diseases include live attenuated strains that produce infection without inducing disease, such as the Sabin polio vaccine. Such strategies are not practically applicable to HiV-1 because the safety of attenuated...

Bacillus species and diseases

That the etiological agent of anthrax is a Bacillus species, namely B. anthracis, was mentioned at the outset. The pathogenic potential of ASB other than B. anthracis has become increasingly recognized in the past three decades with a proliferation of reports implicating Bacillus species, particularly B. cereus, in distinct emetic and diarrheal types of food poisoning and in infections of immunocompromised or otherwise debilitated hosts (e.g. alcoholics, diabetics), in mixed or secondary...

Immunogenetics and disease association

Adrenal autoimmunity may be a heterogeneous condition, as suggested by reports that Addisons disease is inherited in at least three different fashions autosomal recessive, autosomal dominant with decreased penetrance and X-linked recessive. Inherited susceptibility to autoimmune Addisons disease is linked to HLA-DR3 and or DR4, except when the disease occurs as part of type 1 autoimmune polyglandular syndrome. A high prevalence of other autoimmune diseases (ovarian failure, Graves disease,...

Environmental factors

Susceptibility to IDDM is determined by genetic factors however, the concordance rate for IDDM between monozygotic twins approaches only about 35 , suggesting that as well as genetic factors, non-genetic environmental factors influence the clinical expression of this disease. Viruses, toxins, diet and stress have all been implicated as possible environmental determinants of IDDM. There are at least two different mechanisms by which viruses cause IDDM. One mechanism involves the direct infection...

Humanmouse hematopoietic chimeras

Successful xenogeneic bone marrow transplants between close species such as rat and mouse have in the past been demonstrated. Could human bone marrow cells be engrafted in lethally irradiated mice This question is of particular relevance to acquired immune deficiency syndrome (AIDS) research, as human immunodeficiency virus (HIV) does not cause AIDS in any other species except in humans, and it is believed that the presence of human CD4 helper T cells is a reprequisite to infection. If such...

Detecting immune complexes in bodily fluids and tissues

Detection of immune complexes in clinical samples is of interest in a number of human and animal diseases. Furthermore, in countless test systems, immune complexes are the in vitro reaction product of laboratory diagnostic tests for detection of either specific antibodies or antigens. For demonstration of in vivo formed immune complexes in serum or other body fluids, where the antigen involved is unknown, two approaches may be pursued 1) quantitative estimation of immune complexes with...

Diagnosis of drug allergy

Allergic reactions to drugs must be distinguished from similar clinical phenomena of different causes. Two forms of immunologic diagnosis then must be made identification of the specific cause of the reaction, and identification of the immunopathologic Table 1 Clinical classification of allergic reactions to drugs Serum sickness-like reactions Vasculitis syndromes Drug-induced lupus erythematosus and other autoimmune syndromes Pseudolymphoma reactions Pseudoallergie reactions Cutaneous...

Gammaglobulin for prophylaxis and disease prevention

The use of intramuscular gammaglobulin as a prophylaxis against infectious disease in persons exposed to hepatitis A ha established therapeutic benefit. Intramuscular immunoglobulin is also recommended for nonimmune women exposed to rubella in early pregnancy, and for infants or immunosuppressed persons exposed to measles. Specific high-titered preparations of gammaglobulin are also available for prevention of disease following exposure to chicken pox (for immunosuppressed individuals) or...

Liverspecific autoantigen

A liver-specific autoantigen as the target for immune-mediated damage in autoimmune hepatitis has not yet been identified. Crude preparations of liver cells and liver cell membrane preparations have been examined in various ways for reactivity with serum or peripheral blood T cells from patients with autoimmune hepatitis with promising but not unequivocal results. No liver-specific autoantigen has yet been identified by techniques applied successfully in other autoimmune disease, namely...

Clinical tests for allergy

These are the most common tests in atopy and they are characterized by an itchy wheal and erythema at the introduction of an antigen into the skin in an allergen-sensitized individual. The reaction site is small, allowing a great number of tests to be done at once. The skin prick test consists of a biphasic reaction. The immediate phase lasts about 1 h, and is caused by the release of histamine from degranu-latory mast cells. This is often followed by a late reaction, lasting several hours,...

Safety of gammaglobulin

A major concern surrounding the infusion of blood and blood products is the potential for the transmission of viruses. Although there was previously a risk of infection with hepatitis C for patients who received factor VIII and factor IX concentrates, human immunoglobulin concentrates have not historically been noted for the transmission of hepatitis. However, there have been a few cases of hepatitis on record that were traceable to injections of intramuscular immunoglobulins, and there have...

Hepatitis E virus

Hepatatis E virus (HEV) is a member of the Calicivir-idae family. Hepatitis E (HE) is a self-limiting disease, similar to hepatitis A, with no known tendency for chronicity. Hepatitis E occurs as large scale epidemics in developing countries, and also as sporadic cases. Outbreaks have been reported and confirmed either serologically or with the reverse transcriptase polymerase chain reaction (RT-PCR) in over 30 countries throughout the world. The primary source of infection is usually drinking...

Idiopathic inflammatory myopathy

The idiopathic inflammatory myopathies, which include polymyositis, dermatomyositis and inclusion body myositis, are inflammatory diseases of muscle which cause weakness, and less frequently pain, of the large proximal muscles of the trunk and limbs. The inflammatory lesion with primarily lymphocytes results in damage and subsequent attempts at repair of the muscles with release of the muscle enzymes creatine kinase, aldolase, aspartate aminotransferase and lactate dehydrogenase. The muscle...

Clinical aspects in human medicine

Immune complexes are found in the circulation and or other biological fluids of patients with a large spectrum of diseases not resembling each other, such as autoimmune, infectious and neoplastic disorders. This proves that elimination of antigens in the stage of immune complexes is a common feature to many diseases, and symptoms may nor necessarily result from their presence. In fact, in many circumstances, it is not possible to differentiate between a role for immune complexes in...

Hepatitis A Virus Infection And Immunity

Ian D Gust, CSL Ltd, Parkville, Victoria, Australia Hepatitis A is an acute, self-limiting infection of the liver, caused by an enterically transmitted picorna-virus. As the virus is not cytolytic, liver cell damage is assumed to be immunologically mediated. While frequently asymptomatic, especially in the young, infection occasionally results in fulminant hepatitis and death. Recovery from the disease is accompanied by lifelong protection against reinfection. Protection is mediated by...

Historical perspective

In 1899, Caesar Boeck described a patient with lym-phadenopathy and multiple skin nodules with characteristic epithelioid granulomas on histologic examination he proposed the term 'multiple benign sarkoids' for this condition. The view that sarcoidosis is a multisystem disease was first clearly expressed by Jorgan Schaumann in 1914. Thirty years later, Sven Lofgren observed that sarcoidosis frequently presents with asymptomatic bilateral hilar adenopathy or with erythema nodosum. For many...

A final common immunocytotoxic pathway in CAH

The occurrence of autoantibody to various liver cell constituents, together with histological appearances of CAH in diseases that are not primarily attributable to an autoimmune process, has led to the idea that an immune-mediated attack on liver cells can supervene as a 'final common immunocytotoxic pathway' in liver diseases with different initiating causes. Whilst this may indeed occur, the features of this postulated 'secondary' autoimmune hepatitis do not really simulate those of the...

Mechanisms of hepatocellular damage

The mechanisms of hepatocellular damage in chronic active hepatitis will vary according to the particular cause. In CAH-B there are two likely processes, a specific immune deficiency to critical antigens of the virus, probably the surface antigen, that allows a state of tolerated infection to occur, and a nonelimin-ative attack by cytotoxic T cells on epitopes of the core antigen (HBcAg) expressed with class I major histocompatibility complex (MHC) molecules on the liver cell membrane. In...

Immune gene translocations associated with DNA repair deficiency

The cutting and repasting of DNA segments during the process of legitimate immune gene rearrangements must surely involve some components of the normal DNA repair machinery. Increased frequency of chromosomal aberrations are indeed observed in normal cells following severe DNA damage and in lymphocytes of individuals with a DNA repair deficiency. Several DNA repair deficiencies are also characterized by an increased risk of malignancies. Patients with ataxia telangiectasia (AT), for example,...

Phenotypic expression due to multifactorial inheritance

Most human phenotypic traits and diseases are not determined by a single-gene effect rather they are caused by the interaction of genes and the environment, and are thus known as multifactorial conditions. The inheritance of multifactorial traits (also known as polygenic traits because of the involvement of multiple genes in determining a single trait) account for much of the normal variation (e.g. height, weight, skin color and intelligence), and many common diseases, including cardiovascular...

Nutritional regulation of immune function in low birth weight infants and in the elderly

There are many striking similarities between the two ends of the age spectrum. Both neonates and the elderly have suboptimal immune responses and are susceptible to infection. When nutritional deficiency complicates the picture, impairment of immuno-competence is more marked and longer-lasting. The immune system develops during fetal life and the first few months after birth. If an infant is born preterm or if he or she exhibits growth retardation as a result of a number of environmental...

Drugindependent autoimmune hemolytic anemias

In these cases the antibody reacts with the red cell in the absence of the drug. The anti-red cell autoantibodies seem to be serologically identical to those of 'idiopathic' warm-type autoimmune hemolytic anemia. The great majority of cases have followed the use of the anti-hypertension drug a-methyldopa (Aldomet). The red cells are coated with IgG and the serum contains autoantibodies which characteristically have Rh specificity. In patients receiving a-methyldopa the autoantibody is often...

Hepatitis C Virus Infection And Immunity

William L Irving, Department of Microbiology, University of Nottingham, Nottingham, UK Hepatitis C virus (HCV) was first characterized in 1989, following successful cloning from copy DNA extracted from infectious chimpanzee plasma. The natural route of infection is unknown, but HCV is blood borne, and therefore high-risk groups for infection include intravenous drug users and recipients of unscreened blood and blood products (e.g. hemophiliacs). Sexual transmission does not appear to be a major...

Fetalneonatal B cells exhibit a restricted antibody repertoire

It has been shown that the fetal neonatal repertoire of available antibody specificities is restricted. The development of antibody specificities during ontogeny proceeds in a temporally dependent and programmed manner. BALB c mice possess B cells capable of responding to the hapten dinitrophenyl and to the carbohydrate antigen (32,6-fructosan by day 1 after birth however, reproducibly, those B cells bearing the T15 idiotype and responsive to the antigen phosphorylcholine are only apparent at 1...

Lymphocyte Differentiation

John H Kehrl, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA B cell differentiation broadly construed encompasses both the generation of B lymphocytes from precursor or stem cells (i.e. B cell development), as well as their maturation into plasma or memory cells. B cell lymphopoiesis begins in the embryonic yolk sac, switches to the fetal liver, and shortly after birth becomes established in the bone...

Other polyendocrine autoimmunity syndromes

Rarely, diabetes mellitus results from a decreased biological response to a normal amount of insulin. In type A insulin resistance, the problem lies in the insulin receptor, which is quantitatively or qualitatively abnormal, but in the type B syndrome autoantibodies to the insulin receptor produce diabetes mellitus. In vitro, using short-term culture experiments, these antibodies mimic the action of insulin, which may account for the occurrence of hypoglycemia in some patients. More typically,...

The origin of mononuclear phagocytes

During ontogeny, the hematopoietic stem cell - a cell of mesenchymal origin - arises in the yolk sac. In a later stage of gestation, these cells migrate to the fetal liver, where immature mononuclear phagocytes develop hematopoiesis in the liver does not cease until term or the second week after birth, depending on the species. Soon after hematopoiesis begins in the fetal liver, monocytes appear in the circulation only after that does hematopoiesis commence in the bone marrow. Before...

Ontogenetic and phyiogenetic significance of the idiotype network

The rearrangement of DNA segments encoding the specificity of the variable region of the immune receptor of T and B lymphocytes occurs during the development of these lineages. The V region genes are clustered in families. The members of the same family show a high degree of DNA homology. The DNA homology can be observed among certain V gene families of various species. Because the rearrangement of some V genes occurs during ontogeny before the expression of antigen receptor, it appears that...