immunology allergic disorders
Overview of Allergic and Atopic Disorders
Classification of Hypersensitivity Reactions
Hypersensitivity reactions are divided into 4 types (I through IV) by the Gell and Coombs classification. Hypersensitivity disorders often involve more than 1 type. Type I reactions (immediate hypersensitivity) are IgE-mediated. Antigen binds to IgE that is bound to tissue mast cells and blood basophils, triggering release of preformed mediators (eg, histamine, proteases, chemotactic factors) and synthesis of other mediators (eg, prostaglandins, leukotrienes, platelet-activating factor, cytokines). These mediators cause vasodilation, increased capillary permeability, mucus hypersecretion, smooth muscle spasm, and tissue infiltration with eosinophils, type 2 helper T (TH2) cells, and other inflammatory cells. Type I hypersensitivity reactions develop < 1 hour after exposure to antigen. Type I reactions underlie all atopic disorders (eg, Atopic Dermatitis (Eczema) , allergic Atopyis an exaggerated IgE-mediated immune response; all atopic disorders are type I hypersensitivity disorders. Allergyis any exaggerated immune response to a foreign antigen regardless of mechanism. Thus, all atopic disorders are considered allergic, but many allergic disorders (eg, Hypersensitivity Pneumonitis ) are not atopic. most commonly affect the nose, eyes, skin, and lungs. These disorders include Allergic Conjunctivitis , extrinsic Type II reactions (antibody-dependent cytotoxic hypersensitivity) result when antibody binds to cell surface antigens or to a molecule coupled to a cell surface. The surface-bound antigen-antibody structure (as opposed to the circulating antigen-antibody complex in type III hypersensitivity) activates cells that participate in antibody-dependent cell-mediated cytotoxicity (eg, natural killer cells, eosinophils, macrophages), complement, or both. The result is cell and tissue damage. Disorders involving type II reactions include Rejection of an organ transplant, Coombs-positive Type III reactions (immune complex disease) cause inflammation in response to circulating antigen-antibody immune complexes deposited in vessels or tissue. These complexes can activate the complement system or bind to and activate certain immune cells, resulting in release of inflammatory mediators. Consequences of immune complex formation depend in part on the relative proportions of antigen and antibody in the immune complex. Early in the immune response, there is excess antigen with small antigen-antibody complexes, which do not activate complement. Later, when antigen and antibody are more balanced, immune complexes are larger and tend to be deposited in various tissues (eg, glomeruli, blood vessels), causing systemic reactions. The isotype of induced antibodies changes during an immune response, and the isotype, glycosylation, size, and charge of the complex’s components contribute to the clinical response. Type III disorders include serum sickness, Systemic Lupus Erythematosus (SLE) , Type III reactions develop 4 to 10 days after exposure to antigen and, if exposure to the antigen continues, can become chronic. Type IV reactions (delayed hypersensitivity) do not involve antibodies but are mediated by T cells. T cells, sensitized after contact with a specific antigen, are activated by continued exposure or reexposure to the antigen; they damage tissue by direct toxic effects or through release of cytokines, which activate eosinophils, monocytes and macrophages, neutrophils, or natural killer cells. Disorders involving type IV reactions include Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) , Latex sensitivity is an exaggerated immune response to water-soluble proteins in latex products (eg, rubber gloves, dental dams, condoms, tubing for respiratory equipment, catheters, enema tips with inflatable latex cuffs). Beginning in the late 1980s, incidence increased among health care workers when emphasis on universal precautions resulted in routine use of latex gloves. Reactions to latex may be Acute (IgE-mediated) Delayed (cell-mediated) Acute reactions cause urticaria and anaphylaxis; delayed reactions cause dermatitis. After health care workers wear latex gloves, the skin often becomes irritated and crusted, but this reaction is usually chemical irritation, not latex allergy. Diagnosis of latex sensitivity is based primarily on history. Skin testing and assays for detecting IgE antilatex antibodies are available. Treatment is avoidance of latex. For the most part, health care institutions are now latex-free, and the incidence of latex allergy has dramatically decreased.* *SeeRaulf M: Current state of occupational latex allergy.Curr Opin Allergy Clin Immunol20 (2):112–116, 2020. 