Type III hypersensitivity reactions are caused by the deposition of immune complexes in blood vessel walls and tissues. Repeated antigen exposure leads to sensitization with the production of an insoluble antigen-antibody complex. As these complexes are deposited in tissues, the complement system is activated, macrophages and leukocytes are attracted, and immune-mediated damage occurs. Common skin conditions in this category include allergic vasculitis and erythema nodosum. Pulmonary reactions include hypersensitivity pneumonitis, characterized best by farmer’s lung, which is a reaction to thermophilic actinomycetes found in moldy hay. Chemicals such as toluene diisocyanate, phthalic anhydride, and trimetallic anhydride can cause bathtub refinisher’s lung, epoxy resin lung, and plastic worker’s lung, respectively.

Farmer’s lung and the Arthus reaction (Fig. 1) are examples of local immune complex diseases. Poststreptococcal glomerulonephritis is an example of a circulating immune complex disease, as in systemic lupus erythematosus (SLE). Immune complexes are lattices of antigen and antibody that may be localized to the site of antigen production or may circulate in the blood. Immune complexes are produced as part of the normal immune response and are usually cleared by mechanisms involving complement. However, they cause disease in various situations. Failure to clear immune complexes can result from the saturation of mechanisms involving excessive ongoing production of immune complexes, as well as antigenemia caused by chronic infection.

Fig1. Arthus reaction.  In these two reactions of the skin of a  rabbit, the larger reaction has an extensive zone of erythema and  edema surrounding its necrotic center. (From Markell EK, Voge M: Medical parasitology, ed 5, Philadelphia, 1981, WB Saunders.)

The formation of immune complexes under normal conditions protects the host because they facilitate the clearance of various antigens and invading microorganisms by the mono nuclear phagocyte system. In immune complex reactions (disease), antigen-antibody complexes form in the soluble or fluid phase of tissues or in the blood and assume unique bio logical functions, such as interaction with complement and with cellular receptors.

Other type III (immune complex) reactions include serum sickness and certain aspects of autoimmune diseases (e.g., glomerulonephritis in SLE). Circulating soluble immune complexes are responsible for or associated with various human diseases in which exogenous and endogenous antigens can trigger a pathogenic immune response and result in immune complex disease (Table 1).

Table1. Diseases Associated With Immune Complexes

Mechanism of Tissue Injury

Type III reactions are caused by IgG, IgM, and possibly other antibody types. Immune complexes can exhibit a spectrum of biological activities, including suppression or augmentation of the immune response by interacting with B and T cells, inhibition of tumor cell destruction, and deposition in blood vessel walls, glomerular membranes, and other sites. These deposits interrupt normal physiologic processes because of tissue dam age secondary to the activation of complement and resulting activities such as mediating immune adherence and attracting leukocytes and macrophages to the sites of immune complex deposition. The release of enzymes and possibly other agents damages the tissues. There are three general anatomic sites of antigen-antibody interactions:

1. Antibody can react with soluble antigens in the circulation and form immune complexes that may disseminate and lodge in any tissue with a large filtration area and cause lesions of immune complex disease.

2. Antibody can react with antigen secreted or injected locally into the interstitial fluid. The classic example is the experimental Arthus reaction, the basic model of local immune complex disease (see Fig. 1).

3. Antibody can also react with structural antigens that form part of the cell surface membranes or with fixed intercellular structures such as the basement membranes. Systemic immune complex disease serum sickness is an example of soluble and tissue-fixed antigen involvement.

Clinical Manifestations

 The persistence of immune complexes in the blood circulation is not inherently harmful. Immune complex disease develops when these circulating complexes are not cleared from the circulation by phagocytosis and are subsequently deposited in certain tissues. Serum Sickness. Acute serum sickness develops within 1 to 2 weeks after initial exposure or repeated exposure by injection of heterologous serum protein. There is no preexisting antibody and the disease appears as antibody formation begins. The hall mark of serum sickness is the protracted interaction between antigen and antibody in the circulation, with the formation of antigen-antibody complexes in an environment of antigen excess. Chronic serum sickness can be experimentally induced if small amounts of antigen are given daily and represent just enough antigen to balance antibody production.

Autoimmune Disorders. SLE is an autoimmune disorder characterized by autoantibodies that form immune complexes with autoantigens, which are deposited in the renal glomeruli. As a consequence of this type III hypersensitivity reaction, glomerulonephritis (inflammation of capillary vessels in the glomeruli) develops.

Testing for Type III Hypersensitivity Reactions Specific autoimmune disorders, such as rheumatoid arthritis, have specific assays for detecting and monitoring the autoimmune disorder. Common assays use latex agglutination, nephelometry, and chemiluminescence techniques.

Fluorescent staining of tissue biopsy specimens can be used to observe the deposition of immune complexes in tissues. Staining patterns and affected tissues can assist in disease diagnosis and prognosis. Another laboratory assay used in assessment is the quantitation of complement (C3 and C4 components).

Treatment

 The most direct treatment is avoidance of the offending anti gen. Corticosteroids block some of the damage caused by effector cells. Cyclophosphamide is an alkylating agent that impairs DNA synthesis and prevents rapid proliferation of cells (e.g., lymphocytes reduce B cell proliferation).

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وفد العتبة العباسية المقدسة يهنئ الأمين العام للعتبة الكاظمية المقدسة بمناسبة تعيينه

العتبة العباسية المقدسة تنظم دورة في الإسعافات الأولية لعدد من ملاكاتها

في مستشفى الكفيل.. فريق طبي ينجح بمعالجة مسن يعاني من انسداد القناة الصفراوية

المجمع العلمي يقيم جلسةً قرآنية لتعليم أحكام التلاوة في النجف الأشرف

المزيد

الآخبار الصحية

الأطعمة الحارة.. "سر صغير" يغير صحة قلبك وعقلك

وباء صامت.. الملايين حول العالم مصابون بالسكري دون أن يعلموا !

لماذا ينصح بتناول تفاحة يوميا؟

8 فواكه طبيعية تمنحك نوما هنيئا.. وتخلصك من الأرق

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الآخبار التكنلوجية

ثلاث علامات على وجود مشاكل خطيرة في محرك السيارة ؟

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مركبة فضاء تعثر على دليل عن وجود حياة قديمة على المريخ

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المزيد

مواضيع ذات صلة

Influenza virus immunology

Type II Antibody-Dependent, Complement-Mediated Cytotoxic Reactions

Immunologic Manifestations of Rubella infection

Antigen presentation

Cytokines

Structure of MHC Molecule

MHC Genes and Their Products

Macrophage

B Lymphocytes

T Lymphocytes

Immunologic Manifestations of Infectious Mononucleosis

Peripheral Lymphoid Organs