In Type II hypersensitivity reactions, which of the following mechanisms is responsible for cell lysis in Graves' disease?

Explanation

## Type II Hypersensitivity: Antibody-Mediated Cytotoxicity **Key Point:** Type II hypersensitivity is mediated by **IgG antibodies** binding to cell-surface or tissue-bound antigens, leading to cell destruction via two primary mechanisms: **ADCC** and **complement activation**. ### Graves' Disease Pathophysiology In Graves' disease (autoimmune thyroiditis): - IgG autoantibodies bind to **TSH receptors** on thyroid follicular cells - This triggers: 1. **Complement-dependent cytotoxicity (CDC):** Classical complement pathway activation → C3b/C4b deposition → MAC formation → cell lysis 2. **Antibody-dependent cellular cytotoxicity (ADCC):** IgG Fc region binds to Fc receptors on NK cells, macrophages, and neutrophils → release of cytotoxic granules (perforin, granzyme) → target cell apoptosis ### Type II Hypersensitivity Mechanisms | Mechanism | Effector | Outcome | Examples | |-----------|---------|---------|----------| | ADCC | NK cells, macrophages, neutrophils | Cell lysis via granule release | Graves' disease, Goodpasture syndrome | | CDC | Complement system (C1q → MAC) | Membrane perforation, cell lysis | Graves' disease, autoimmune hemolytic anemia | | Opsonization | Macrophages, neutrophils | Phagocytosis of antibody-coated cells | Hemolytic disease of newborn | | Receptor blockade | IgG antibodies | Functional inhibition (no cell death) | Myasthenia gravis | **High-Yield:** Graves' disease involves **both ADCC and CDC**, making it a classic example of Type II hypersensitivity with **cytotoxic and stimulatory** components (TSH receptor agonism also occurs, but cell lysis is via ADCC/CDC). **Clinical Pearl:** The presence of **TSH receptor antibodies (TRAb)** in Graves' disease can be detected clinically; high titers correlate with disease severity and risk of neonatal thyroiditis. **Mnemonic:** **Type II = Antibodies + Cells = ADCC & CDC**. Think: IgG on cell surface → NK cells attack (ADCC) or complement attacks (CDC).