## Type 1 Lepra Reaction: Immunopathology **Key Point:** Type 1 lepra reaction (reversal reaction) is a delayed-type hypersensitivity reaction (Type IV) driven by Th1 cytokines, primarily **IFN-γ and TNF-α**. ### Mechanism Type 1 reaction occurs due to: 1. Delayed-type hypersensitivity to Mycobacterium leprae antigens 2. Th1-mediated immune response with elevated IFN-γ and TNF-α 3. Activation of macrophages and CD8+ T cells 4. Inflammation at pre-existing lesion sites ### Cytokine Profile Comparison | Reaction Type | Primary Cytokines | Mechanism | Timing | |---|---|---|---| | **Type 1 (Reversal)** | IFN-γ, TNF-α | Th1 (Cell-mediated) | During or after treatment | | **Type 2 (ENL)** | IL-10, TGF-β, IL-6 | Immune complex (Type III) | During treatment (BL/LL) | **High-Yield:** IFN-γ is the hallmark Th1 cytokine; TNF-α amplifies the inflammatory cascade in Type 1 reaction. This Th1 dominance explains the delayed-type hypersensitivity pattern and the clinical presentation of inflammation at existing lesion sites. **Clinical Pearl:** Type 1 reactions occur in **borderline forms** (BT, BL) of leprosy and reflect upgrading or downgrading of immunity during treatment. 
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