Type I Hypersensitivity

Overview
  • Type I Hypersensitivity is one of the basic mechanisms by which immune-mediated injury to host tissues can occur. The reaction occurs due to inappropriate secretion of potent vasoactive, bronchoactive, and inflammatory mediators by the anti-parasitic leukocytes (Mast Cells, Basophils, and Eosinophils) in response to environmental antigens. When activation is localized, Type I Hypersensitivity is not serious; however, catastrophic activation of anti-parasitic cells can be life-threatening.
Pathogenesis
  • Overview
    • Inappropriate activation of anti-parasitic cells occurs when environmental antigens cross-link pre-formed antigen-specific IgE bound to Fc Receptors on the cells' surface. Development of antigen-specific IgE requires an initial exposure to the environmental antigen during which no clinical consequences arise. Only upon later re-exposure to the environmental antigen, when antigen-specific IgE has been formed and deposited on the cell surface, are anti-parasitic leukocytes activated and thus cause clinical consequences. The time between initial and re-exposure can be weeks, months, or years and only depends on how long antigen-specific IgE remains. In general, this is a lifetime.
  • Initial Exposure
    • Before a Type I reaction can occur, IgE specific to the environmental antigen must be produced and deposited on the membrane of mast cells and basophils. Initial encounter with the environmental antigen results in the proliferation of antigen-specific B-cells and their isotype switching to IgE as described in Humoral Immunity. The antigen-specific IgE secreted by the B-cells then enters circulation and binds to Fc Receptors on basophils and mast cells. The end-result of this initial phase is a population of anti-parasitic leukocytes which possess membrane-bound IgE specific to the environmental antigen. Re-exposure to the environmental antigen will cause cross-linking of this surface IgE, inducing activation of these cells and thus release of potent vasoactive and inflammatory mediators.
  • Re-exposure
    • Cross-linking of membrane-bound IgE on the anti-parasitic cells causes release of vasoactive and inflammatory mediators in two phases. The first, early phase which lasts less than an hour, is associated with release of pre-formed granules which contain vasoactive, bronchoactive, and inflammatory molecules the most important of which is Histamine. These molecules cause vasodilation and increase vascular permeability along with bronchoconstriction. The second, late phase which can last days, is associated with de novo production of cytokineswhich primarily recruit eosinophils to the tissue. Recruited eosinophils then cause a variety of tissue damage.
Clinical Consequences
  • Overview
    • The clinical consequences of a Type I Hypersensitivity reaction largely depend on the route and severity of antigen exposure.
  • Systemic Exposure
    • Systemic exposure to a large dose of antigen can cause catastrophic and systemic release of vasoactive, bronchoactive, and inflammatory mediators which manifests as Anaphylactic Shock.
  • Local Exposure
    • Local exposure to antigen usually causes a localized release of vasoactive, bronchoactive, and inflammatory mediators which can manifest differently depending on the exposed organ.
    • Epidermal Exposure: Urticaria
    • Inhalation: Extrinsic Asthma
    • Ingestion: Diarrhea