type II hypersensitivity

Type II hypersensitivity reactions occur when IgG or IgM antibodies target antigens present on the surface of cells or within the extracellular matrix (as opposed to soluble antigens forming immune complexes, as in type III). There are three main mechanisms of tissue damage: (1) Complement-dependent cytotoxicity — antibody binding activates the classical complement pathway, leading to formation of the membrane attack complex (MAC) and cell lysis (e.g., autoimmune hemolytic anemia, transfusion reactions, hyperacute transplant rejection). (2) Antibody-dependent cell-mediated cytotoxicity (ADCC) — NK cells and other effector cells recognize the Fc portion of bound antibodies and destroy the target cell without phagocytosis. (3) Antibody-mediated cellular dysfunction — antibodies bind to cell surface receptors and either stimulate or inhibit normal receptor function without necessarily destroying the cell (e.g., Graves disease, where anti-TSH receptor antibodies stimulate thyroid hormone production; myasthenia gravis, where antibodies block acetylcholine receptors at the neuromuscular junction).

Clinically important examples include: Goodpasture syndrome (anti-glomerular basement membrane antibodies causing pulmonary hemorrhage and glomerulonephritis), Autoimmune hemolytic anemia and thrombocytopenia (antibodies against RBC or platelet antigens), Pemphigus vulgaris (anti-desmoglein antibodies causing skin blistering), Rheumatic fever (antibodies against streptococcal M protein cross-reacting with cardiac tissue — molecular mimicry), Hemolytic disease of the newborn (Rh incompatibility), and Graves disease/Myasthenia gravis (receptor-mediated, sometimes classified separately as 'type V').

Diagnosis often involves direct or indirect Coombs test to detect antibody or complement bound to red blood cells, useful in autoimmune hemolytic anemia and hemolytic transfusion reactions. Understanding the distinction between the four classic Gell and Coombs hypersensitivity types (I: IgE-mediated immediate, II: cytotoxic antibody, III: immune complex, IV: T cell-mediated delayed) is essential for the USMLE, as many autoimmune and transfusion-related diseases are tested through this lens.