The Gell-Coombs classification categorizes immune-mediated hypersensitivity reactions into four types based on mechanism. Type I (Immediate/Anaphylactic): IgE-mediated; antigen cross-links IgE bound to mast cell/basophil FcεRI receptors, causing degranulation and release of histamine, leukotrienes, prostaglandins, and tryptase. Onset within minutes. Clinical examples: anaphylaxis, allergic rhinitis, asthma (allergic), urticaria, food allergy, drug allergy (penicillin anaphylaxis). Treatment: epinephrine (first-line for anaphylaxis), antihistamines, corticosteroids. Type II (Cytotoxic/Antibody-Mediated): IgG or IgM antibodies bind cell-surface antigens, activating complement and/or recruiting NK cells (ADCC), leading to cell destruction. Examples: autoimmune hemolytic anemia (warm = IgG, cold = IgM), hemolytic transfusion reaction, hemolytic disease of the newborn (Rh incompatibility), Goodpasture syndrome (anti-GBM antibodies), myasthenia gravis (anti-AChR antibodies — antibodies block receptor function), Graves disease (TSI antibodies stimulate TSH receptor). Type III (Immune Complex): antigen-antibody complexes (IgG/IgM) deposit in tissues, activate complement, and recruit neutrophils causing tissue damage. Examples: serum sickness, lupus nephritis (SLE), post-streptococcal glomerulonephritis, polyarteritis nodosa, Arthus reaction (localized), hypersensitivity pneumonitis. Type IV (Delayed/Cell-Mediated): T-cell mediated (no antibody involvement); sensitized T cells release cytokines upon re-exposure to antigen, recruiting macrophages and causing tissue damage. Onset 24-72 hours....