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Allergic, hypersensitivity reactions are amplified immunologic responses triggered by allergen, or antigen stimulation in previously sensitized individuals. The sensitization occurs from the identical antigen that triggers future allergic reaction, or from a different antigen sharing similar molecular structures.
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Four main hypersensitivity reactions are classified by the immune system components involved:
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Type I reactions are anaphylactic or immediate-type hypersensitivity reactions. Antigens bind to and cross-link IgE antibodies, causing mast cells to release inflammatory mediators. Examples of Type I reactions include anaphylaxis, allergic rhinitis, and asthma.
Type II reactions involve the activation of the classic complement system by IgG or IgM antibodies, which causes lysis and destruction of cells. Examples include ABO incompatibility, drug-induced hemolytic anemia, and heparin-induced thrombocytopenia.
Type III reactions primarily involve immune complexes of antigens and antibodies bound together. Deposition of immune complexes in tissues activates neutrophils and triggers the complement system. An example of Type III reaction is serum sickness.
Type IV reactions, or delayed hypersensitivity reactions, are characterized by antigen-to-lymphocyte binding. They primarily result in proliferation of cytotoxic T lymphocytes with the purpose of extinguishing antigen-bearing triggering cell. These particular reactions occur within 24 hours, peak from 40-80 hours and resolve by 96 hours. Examples include graft-versus-host reactions, tuberculin immunity as well as contact dermatitis.
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ANAPHYLAXIS: PATHOPHYSIOLOGY
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Type I immediate hypersensitivity reactions begin when a susceptible individual is exposed to an antigen. During primary exposure, antigen is processed by the antigen-presenting cell (APC). APC then presents antigen’s processed peptide to CD4+ T cells, inducing CD4+ T cell production of IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These factors stimulate B cells to switch their immunoglobulin production to peptide-specific IgE. Newly produced IgE antibodies are released from B cells and bind to IgE receptors on mast cells and basophils in peripheral tissue and circulation. The IgE antibodies are fixated on the membrane of basophils and mast cells by the Fc receptors. Upon secondary exposure, the allergen binds to IgE, causes cross-linking, and stimulates the basophils and mast cells to degranulate and release their inflammatory vasoactive mediators—prostaglandins, leukotrienes, histamines, and tryptase. The sudden release of these mediators causes arteriolar vasodilatation with increased vascular permeability, bronchiolar smooth muscle constriction, and increased mucus secretions. The degree of immediate hypersensitivity responses varies from mild allergic rhinitis or atopic dermatitis to life-threatening angioedema and anaphylaxis.
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Anaphylaxis is a severe, unanticipated, Type I reaction with a variety of respiratory, cardiovascular, gastrointestinal, and cutaneous signs and symptoms (Table 105-1). These manifestations are driven by active mediators, including histamines, released by antigen-IgE stimulated basophils and mast cells, which cause smooth muscle contraction, vascular permeability, and leukocyte and platelet aggregation. Severe symptoms include cardiovascular collapse and pulmonary edema.
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