## Type II Hypersensitivity in Graves' Disease **Key Point:** Graves' disease is a unique Type II hypersensitivity reaction in which autoantibodies (IgG) against TSH receptors act as **agonists** rather than blocking antibodies, causing pathological activation of thyroid function. ### Pathophysiology 1. **Autoantibody Production:** IgG antibodies against TSH receptor (TSH-R) are generated 2. **Receptor Activation:** These antibodies bind to TSH-R and mimic TSH, causing **continuous stimulation** 3. **Thyroid Hyperfunction:** Results in: - Increased thyroid hormone synthesis (T3, T4) - Thyroid cell proliferation and hypertrophy - Thyroid enlargement (diffuse goiter) 4. **Clinical Manifestations:** Hyperthyroidism, exophthalmos, pretibial myxedema **High-Yield:** Graves' disease demonstrates **stimulating antibodies** (unlike most Type II reactions which are blocking). This is why TSH levels are suppressed despite high thyroid hormone levels. ### Type II Hypersensitivity Mechanisms | Mechanism | Example | Outcome | |-----------|---------|----------| | **Stimulating antibodies** | Graves' disease (anti-TSH-R) | Receptor activation → hyperfunction | | **Blocking antibodies** | Myasthenia gravis (anti-AChR) | Receptor blockade → loss of function | | **Cytotoxic antibodies** | Goodpasture syndrome (anti-GBM) | ADCC + complement → tissue destruction | | **Immune complex** | Type III reaction | Not Type II | **Clinical Pearl:** The presence of TSH receptor antibodies (TRAb or TSI) is diagnostic for Graves' disease and helps distinguish it from other causes of hyperthyroidism like thyroiditis or toxic nodule.
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.