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Asriani M. Chiu 14
Atopy is a result of a complex interaction between multiple genes and environmental factors. It implies specific IgE-mediated diseases, including allergic rhinitis, asthma, and atopic dermatitis. An allergen is an antigen that triggers an IgE response in genetically predisposed individuals.
Hypersensitivity disorders of the immune system are classified into four groups, based on the mechanism that leadsto tissue inflammation (Table 77-1). Type I reactions are triggered by the binding of antigen to high-affinity IgE receptors on the surface of tissue mast cells, circulating basophils,or both, causing the release of preformed chemical mediators, such as histamine and tryptase, and newly generatedmediators, such as leukotrienes, prostaglandins, and platelet-activating factor. These mediators contribute to the development of allergic symptoms, with anaphylaxis as the mostprofound symptom. Several hours after the initial response, a late-phase reaction may develop with an influx of other inflammatory cells such as basophils, eosinophils, monocytes, lymphocytes, and neutrophils, and their inflammatorymediators. Recruitment of these cells leads to more persistentand chronic symptoms.
Type II (antibody cytotoxicity) reactions involve IgM, IgG, or IgA antibodies binding to the cell surface and activating the entire complement pathway resulting in lysis of the cell or release of anaphylatoxins, such as C3a, C4a, and C5a (see Chapter 75). These anaphylatoxins trigger mast cell degranulation, resulting in inflammatory mediator release. The target can be cell surface membrane antigens, such as red blood cells (hemolytic anemia); platelet cell surface molecules (thrombocytopenia); basement membrane molecules in the kidney (Goodpasture syndrome); the alpha chain of the acetylcholine receptor at the neuromuscular junction (myasthenia gravis); and thyroid-stimulating hormone receptor on thyroid cells (Graves disease).
Type III (immune complex) reactions involve the formation of antigen-antibody or immune complexes that enter into the circulation and are deposited in tissues such as blood vessels and filtering organs (i.e., liver, spleen, and kidney). These complexes initiate tissue injury by activating the complement cascade and recruiting neutrophils that release their toxic mediators. Local reactions caused by the injection of antigen
I—Anaphylactic <30 min IgE Pollens, food, Histamine, tryptase, Anaphylaxis, immediate late 2–12 h venom, drugs leukotrienes, urticaria, allergic phase prostaglandins, platelet-rhinitis, allergic activating factor asthma
CSF, Cerebrospinal fluid; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-γ, interferon-γ; TB, tuberculosis; TNF-α, tumor necrosis factor-α.
into tissue are called Arthus reactions. The administration of large amounts of antigen leads to serum sickness, a classic example of a type III reaction. Other type III–mediated reactions include hypersensitivity pneumonitis and some vasculitic syndromes.