Paper I
Question
Write the Cellular events of acute inflammation
Answer
Cellular events of acute inflammation
1. Margination
- As blood flow slows (stasis) due to vasodilatation, leucocytes shift from the central axial column to the periphery, along the endothelial surface
2. Rolling
- Leucocytes loosely and transiently adhere to and roll along the endothelium, mediated by selectins:
- P-selectin (rapidly mobilized from endothelial Weibel-Palade bodies) and E-selectin (induced by cytokines) on endothelium
- L-selectin on leucocytes
- These bind sialylated carbohydrate ligands (e.g., sialyl-Lewis X) on the opposing cell
3. Activation and firm adhesion
- Chemokines displayed on the endothelial surface activate leucocyte integrins (LFA-1, VLA-4), increasing their affinity for endothelial ligands (ICAM-1, VCAM-1)
- This produces firm, stationary adhesion of the leucocyte to the endothelium
4. Transmigration (diapedesis)
- Leucocytes squeeze between endothelial cells at intercellular junctions, mediated by PECAM-1 (CD31) present on both leucocytes and endothelial junctions
- The leucocyte then penetrates the basement membrane using secreted collagenases
5. Chemotaxis
- Leucocytes migrate through the interstitial tissue toward the site of injury, guided by a concentration gradient of chemoattractants (bacterial products, C5a, LTB4, chemokines), via actin-based pseudopod formation
6. Phagocytosis
- Recognition and attachment: Facilitated by opsonins (IgG, C3b) coating the target, recognized by leucocyte Fc and complement receptors
- Engulfment: Cytoplasmic pseudopods extend around the particle, fusing to enclose it within a phagosome, which then fuses with a lysosome to form a phagolysosome
- Killing and degradation: Via reactive oxygen species (respiratory burst, NADPH oxidase), reactive nitrogen species (nitric oxide), and lysosomal enzymes
7. Leucocyte-mediated tissue injury
- Released lysosomal enzymes, reactive oxygen species, and inflammatory mediators can also cause collateral damage to normal host tissue, contributing to some of the pathology seen in various inflammatory diseases