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Type I hypersensitivity (IgE-mediated, immediate) causes mast cell degranulation and acute symptoms. Type II (cytotoxic, antibody-mediated) involves IgG/IgM against cell-surface antigens. Type III (immune complex) deposits antigen-antibody complexes in tissues. Type IV (cell-mediated, delayed) involves Th1 cells and CTLs.
Classify reactions by mechanism and timeline. Study examples: Type I (anaphylaxis, urticaria), Type II (hemolytic anemia, Graves' disease), Type III (serum sickness, post-streptococcal GN), Type IV (contact dermatitis, TB skin test).
Not all allergic reactions are Type I—some involve IgG (Type II or III). Type IV reactions require prior sensitization and take 24–72 hours to develop; they are not 'immediate' hypersensitivity.
The Gell and Coombs classification organizes hypersensitivity reactions by mechanism, not by severity or speed alone. You already know Type I from your prerequisite study. The unifying feature of Types I–III is that they are all antibody-mediated; the distinction is which antibody class is involved and where the damage occurs. Type IV stands apart as entirely cell-mediated, with no antibodies involved. Understanding this mechanistic framework lets you predict clinical timing and tissue pathology rather than memorizing lists of diseases.
Type I (IgE-mediated, immediate hypersensitivity) begins at prior sensitization: antigen drives B cells to class-switch to IgE, which binds the high-affinity FcεRI receptor on mast cells and basophils. On re-exposure, antigen cross-links IgE on mast cell surfaces, triggering degranulation within minutes. Pre-formed mediators (histamine, tryptase) cause the immediate wheal-and-flare; newly synthesized mediators (prostaglandins, leukotrienes) drive the late-phase reaction hours later. Type I is the mechanism of anaphylaxis, allergic asthma, hay fever, and food allergy. Timing is minutes to hours.
Type II (antibody-mediated cytotoxicity) involves IgG or IgM directed against cell-surface antigens. The antibody-coated cell is destroyed by three mechanisms: complement activation (the classical pathway produces MAC and opsonins), antibody-dependent cellular cytotoxicity (NK cells bind IgG via FcγRIII and kill the target), and phagocytosis by Fc-receptor-bearing macrophages. Examples: hemolytic disease of the newborn (anti-Rh IgG crosses the placenta), autoimmune hemolytic anemia, and Graves' disease — where anti-TSH-receptor IgG stimulates rather than destroys, showing that Type II can activate as well as destroy. Timing is hours.
Type III (immune complex–mediated) occurs when antigen-antibody complexes form in excess and deposit in vessel walls, glomeruli, or joints, where they activate complement and recruit neutrophils. It is not the antibody attacking a specific cell; it is the physical deposition of large immune complexes in tissues. The classic example is serum sickness: repeated foreign protein injection generates IgG, complexes form, deposit in kidney glomeruli and vessel walls, and complement activation drives inflammation 1–2 weeks after exposure. Post-streptococcal glomerulonephritis follows the same logic. Timing is days to 2 weeks.
Type IV (delayed, cell-mediated) is mechanistically different: no antibodies are involved. Sensitized Th1 cells recognize antigen presented on MHC II by antigen-presenting cells and release IFN-γ, which activates macrophages and drives granuloma formation. Cytotoxic T lymphocytes (CTLs) kill target cells directly. Because this depends on T cell trafficking and macrophage activation rather than preformed antibody, the reaction peaks at 48–72 hours — hence "delayed." Contact dermatitis (poison ivy, nickel), the tuberculin skin test (PPD), and transplant rejection are canonical Type IV reactions. The PPD test is a deliberate diagnostic application: prior TB exposure generates sensitized Th1 cells that cause an induration at the injection site read at 48–72 hours.