Acute Inflammation: Vascular and Cellular Events
Concept Name
Acute Inflammation
Genetic Loci
IL1B (2q14.1) encodes IL‑1β; NLRP3 (1q44) encodes the inflammasome sensor – mutations cause cryopyrin‑associated periodic syndromes (CAPS). SELE (1q24.2) encodes E‑selectin for neutrophil rolling.
Intracellular Cascade
Tissue injury → mast cell degranulation (histamine, serotonin) → vasodilation and increased permeability. TLR activation → NF‑κB → pro‑inflammatory cytokines (TNF‑α, IL‑1). Endothelial activation → selectin upregulation → neutrophil rolling, adhesion, and transmigration. Chemotaxis via IL‑8, C5a, LTB4.
Required Cofactors
Iron is required for myeloperoxidase in neutrophil granules. Copper is required for lysyl oxidase in wound healing.
Histology Stains
H&E shows neutrophilic infiltrate, edema, and fibrin. Immunohistochemistry for myeloperoxidase (MPO) identifies neutrophils. CD68 stains macrophages in chronic inflammation.
EM Findings
Neutrophils contain characteristic segmented nuclei and cytoplasmic granules (primary/azurophilic, secondary/specific). Phagolysosomes contain ingested bacteria or debris.
Knockout Phenotype
Knockout of IL‑1R1 in mice impairs acute inflammatory response and increases susceptibility to bacterial infections. NLRP3 knockout mice are protected from gout (MSU crystal‑induced inflammation).
Specific Toxins
Colchicine inhibits microtubule polymerization, blocking neutrophil migration and NLRP3 inflammasome activation. NSAIDs inhibit cyclooxygenase, reducing prostaglandin synthesis.