## Type 1 Lepra Reaction: Immunopathogenesis **Key Point:** Type 1 lepra reaction (reversal reaction) is a delayed-type hypersensitivity (Type IV) reaction mediated by Th1 cells and TNF-α. ### Mechanism 1. Occurs in borderline forms of leprosy (BT, BL, LL) 2. Results from delayed-type hypersensitivity to *Mycobacterium leprae* antigens 3. TNF-α is the primary pro-inflammatory cytokine driving inflammation 4. Leads to inflammation in existing lesions and nerves ### Role of TNF-α - Activates macrophages and endothelial cells - Increases vascular permeability - Recruits inflammatory cells to lesions - Causes edema and inflammation in skin and nerves **High-Yield:** TNF-α is the hallmark cytokine of Type 1 reaction; IL-4 and IL-10 are anti-inflammatory and associated with Type 2 reaction (erythema nodosum leprosum). **Clinical Pearl:** Type 1 reaction can occur before, during, or after treatment, and is managed with corticosteroids to suppress TNF-α-mediated inflammation. 
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