Paper I
Question
Chemotaxis
Answer
Chemotaxis is the locomotion of leucocytes along a chemical concentration gradient toward the site of tissue injury or infection, guided by chemoattractant molecules.
Chemoattractants
- Exogenous: Bacterial products, particularly N-formylmethionine-containing peptides
- Endogenous:
- Complement component C5a
- Leukotriene B4 (LTB4)
- Chemokines (e.g., IL-8) — a family of small proteins that act as chemoattractants for specific leucocyte types
Mechanism
- Chemoattractants bind to specific seven-transmembrane G-protein-coupled receptors on the leucocyte surface
- This triggers activation of small GTPases (Rac, Rho, Cdc42), which regulate actin polymerization at the leading edge of the cell
- The cell extends pseudopods (filopodia) by actin polymerization at the front, and contracts at the rear (via actin-myosin interaction), allowing directional crawling movement toward the higher chemoattractant concentration
- Integrins on the leucocyte surface engage with the extracellular matrix, providing traction for movement
Biological significance
- Neutrophils and monocytes migrate to sites of infection/injury within hours, guided by this process, which is central to the effectiveness of the acute inflammatory response
- Both neutrophils and macrophages respond to similar chemotactic agents, though the kinetics differ (neutrophils respond earlier, macrophages later and more sustained)