Immunologic and Inflammatory Mechanisms

The inflammatory response is a complex, coordinated cascade initiated by tissue injury or pathogen recognition, involving vascular changes, cellular recruitment, and chemical mediators. Pattern recognition receptors (PRRs) on innate immune cells — particularly Toll-like receptors (TLRs) — recognize pathogen-associated molecular patterns (PAMPs) from microbes and damage-associated molecular patterns (DAMPs) from injured host cells. TLR activation triggers intracellular signaling through NF-kB and MAPK pathways, inducing transcription of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6), chemokines (IL-8/CXCL8), and inflammatory enzymes (COX-2, iNOS). The arachidonic acid pathway is central to inflammation: phospholipase A2 releases arachidonic acid from cell membrane phospholipids; cyclooxygenase (COX-1 constitutive, COX-2 inducible) converts it to prostaglandins (PGE2 — pain, fever, vasodilation) and thromboxane A2 (platelet aggregation, vasoconstriction); lipoxygenase converts it to leukotrienes (LTB4 — neutrophil chemotaxis; LTC4/D4/E4 — bronchoconstriction, vascular permeability — targets of montelukast). Corticosteroids inhibit phospholipase A2 (blocking both COX and LOX pathways), while NSAIDs inhibit only COX. The complement system activates via classical (antibody-mediated), alternative (spontaneous C3 hydrolysis), and lectin (mannose-binding lectin) pathways, all converging on C3 convertase and generating C3a/C5a (anaphylatoxins — mast cell degranulation, vasodilation), C3b (opsonization),...