Hypersensitivity reactions are excessive or inappropriate immune responses causing tissue damage. Type I (immediate, IgE-mediated, mast cells/basophils) manifests as allergies and anaphylaxis within minutes. Type II (cytotoxic, antibody-mediated) targets cell-surface antigens. Type III (immune complex) deposits complexes in tissues. Type IV (delayed, T cell-mediated) occurs without antibodies.
From your study of adaptive immunity, you know that antibodies and T cells are powerful weapons against pathogens. But what happens when these same weapons are aimed at harmless substances, or when the immune response is disproportionate to the threat? Hypersensitivity reactions are immune responses that cause tissue damage to the host — the immune system working correctly in mechanism but incorrectly in target or magnitude. The Gell and Coombs classification divides these into four types based on the immune effector involved and the timing of the response.
Type I (immediate) hypersensitivity is what most people call "allergies." On first exposure to an allergen (pollen, peanut protein, bee venom), B cells produce IgE antibodies that bind to high-affinity FcεRI receptors on mast cells and basophils, priming them. On re-exposure, the allergen crosslinks adjacent IgE molecules on the mast cell surface, triggering rapid degranulation — the explosive release of preformed mediators like histamine, along with newly synthesized leukotrienes and prostaglandins. These mediators cause vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion — the sneezing, swelling, and itching of allergic rhinitis, or in severe cases, the life-threatening systemic vasodilation and bronchospasm of anaphylaxis. The "immediate" label reflects the speed: symptoms appear within minutes because the mediators are preformed and ready to release.
Type II (cytotoxic) hypersensitivity involves IgG or IgM antibodies directed against antigens on the surface of the host's own cells. The antibody binds the cell surface and triggers destruction through complement activation, opsonization and phagocytosis, or antibody-dependent cellular cytotoxicity (ADCC). Classic examples include hemolytic disease of the newborn (maternal anti-Rh antibodies attacking fetal red blood cells), transfusion reactions from ABO blood group mismatch, and autoimmune hemolytic anemia. Type III (immune complex) hypersensitivity occurs when antigen-antibody complexes form in the blood and deposit in tissues — particularly blood vessel walls, kidney glomeruli, and joint spaces. These deposited complexes activate complement locally, recruiting neutrophils that release enzymes and reactive oxygen species, causing vasculitis, glomerulonephritis, or arthritis. Serum sickness and systemic lupus erythematosus involve Type III mechanisms.
Type IV (delayed-type) hypersensitivity is fundamentally different: it involves T cells rather than antibodies, and symptoms take 24–72 hours to develop because they require T cell activation, proliferation, and migration to the site. The tuberculin skin test (PPD test) is the classic example: injected mycobacterial antigens are recognized by memory T cells from prior exposure, which recruit macrophages and cause localized induration and swelling over 48–72 hours. Contact dermatitis (poison ivy, nickel allergy) is another Type IV response, where small chemical haptens modify skin proteins, creating neoantigens that activate T cells. Understanding which type of hypersensitivity underlies a clinical condition determines the treatment strategy — antihistamines for Type I, plasmapheresis or immunosuppression for Types II and III, and corticosteroids or T cell-targeted therapy for Type IV.