In Graves' disease, TSH receptor antibodies (TRAb) cause hyperthyroidism by acting as Type II hypersensitivity antibodies. Their correct classification is:

• A Immune complex antibodies depositing in the thyroid parenchyma
• B T-cell cytotoxicity mediated by perforin-granzyme mechanism
• C Blocking antibodies causing hypothyroidism via receptor downregulation
• D Stimulatory antibodies acting as TSH-receptor agonists (not cytotoxic) ✓

Explanation

Graves' disease is a prototypic Type II hypersensitivity where antibodies directed against a surface receptor mimic the ligand and stimulate rather than destroy the target cell. TSH receptor-stimulating antibodies (TSAb) bind the TSHR, activating adenylyl cyclase-cAMP pathway, driving thyroid follicular cell growth and unregulated thyroid hormone synthesis independent of TSH. This is distinct from cytotoxic Type II mechanisms (e.g., autoimmune hemolytic anemia). Blocking TSHR antibodies (TBAb) cause hypothyroidism in some patients (atrophic thyroiditis). Immune complexes characterize SLE nephritis (Type III). Perforin-granzyme is the CD8+ CTL mechanism (Type IV).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.