Paper I
Question
Biologic mechanism of Type II hypersensitivity reaction. Give examples of four diseases with type II hypersensitivity as the mechanism of pathologic injury
Answer
Biologic mechanism of Type II hypersensitivity
- Antibody-mediated cytotoxic hypersensitivity, in which IgG or IgM antibodies are directed against antigens present on the cell surface or extracellular matrix
- Tissue/cell injury occurs through:
- Complement-dependent reactions: Antibody binding activates the complement cascade, causing direct cell lysis (membrane attack complex) or opsonization (C3b-mediated) leading to phagocytosis
- Antibody-dependent cell-mediated cytotoxicity (ADCC): Antibody-coated cells are killed by NK cells, macrophages, or eosinophils bearing Fc receptors, without complement or phagocytosis
- Antibody-mediated cellular dysfunction: Antibodies bind to cell-surface receptors and either stimulate or block normal receptor function, without causing cell injury/death
Four diseases with Type II hypersensitivity mechanism
- Autoimmune haemolytic anaemia — antibodies against red cell membrane antigens
- Goodpasture syndrome — antibodies against basement membrane collagen (glomerular and alveolar)
- Myasthenia gravis — antibodies against acetylcholine receptors, blocking neuromuscular transmission (cellular dysfunction mechanism)
- Graves’ disease — antibodies against TSH receptor, causing receptor stimulation (cellular dysfunction mechanism)
- (Others: Pemphigus vulgaris — antibodies against desmoglein; Hemolytic disease of the newborn — Rh incompatibility)