Hypersensitivity

Hypersensitivity is the umbrella term for immune reactions that go too far or aim at the wrong target and so harm the host. The trigger may be a harmless environmental substance, a drug, a microbe or even a self antigen, as in autoimmune disease. The immune system usually has to be sensitized first, so the reaction appears on a second or later exposure. The scheme of Gell and Coombs, still taught everywhere, sorts these reactions into four types by mechanism.

Type I, or immediate, hypersensitivity is IgE-mediated allergy: the allergen cross-links IgE on mast cells, which release histamine within minutes, as in hay fever, food allergy and anaphylaxis. Type II, or cytotoxic, hypersensitivity occurs when IgG or IgM binds antigens on cells, which are then destroyed by complement or phagocytes, as in a mismatched blood transfusion or hemolytic disease of the newborn. Type III is caused by immune complexes, clumps of antibody and soluble antigen that lodge in vessel walls, kidneys and joints and spark inflammation, as in serum sickness and lupus. Type IV, the delayed type, is driven by T cells rather than antibodies and peaks one to three days after exposure, as in poison ivy rash, nickel allergy and a positive tuberculin skin test.

Knowing the type tells clinicians which tests and treatments make sense.