Acute Inflammation: Cellular Events

Leukocyte Extravasation - Cells on the Move

Leukocytes exit vessels to reach injured tissue.

• Steps: Margination → Rolling → Adhesion → Transmigration (Diapedesis).
• Rolling: 📌 Selectins ('S'low down)
  • Endothelial: E-selectin, P-selectin.
  • Leukocyte: L-selectin.
  • Bind Sialyl-Lewis X on leukocytes.
• Adhesion: 📌 Integrins ('I'ntegrate/stop)
  • LFA-1 (leukocytes) binds ICAM-1 (endothelium).
  • VLA-4 (leukocytes) binds VCAM-1 (endothelium).
  • Upregulated by TNF, IL-1.
• Transmigration:
  • PECAM-1 (CD31) at intercellular junctions.
  • Collagenases degrade basement membrane.
• Chemotaxis: Movement towards C5a, LTB4, IL-8.

⭐ PECAM-1 (CD31) is crucial for the transmigration of leukocytes through endothelial intercellular junctions.

Chemotaxis & Activation - Follow the Scent!

• Chemotaxis: Unidirectional leukocyte migration along a chemical gradient towards the site of injury.
• Key Chemoattractants:
  • Exogenous: Bacterial products (e.g., N-formyl-methionine peptides).
  • Endogenous: Complement system (C5a), Arachidonic acid metabolites (Leukotriene B4 - LTB4), Cytokines (Chemokines like IL-8/CXCL8).
  • 📌 Mnemonic: C5a, LTB4, IL-8, Bacterial products - 'Calling Leukocytes In Bacteria'.
• Mechanism: Leukocytes move via pseudopods. Chemoattractants bind to specific G-protein coupled receptors (GPCRs) or Toll-like receptors (TLRs) on leukocytes.
• Leukocyte Activation: Binding of chemoattractants also triggers:
  • Production of arachidonic acid metabolites.
  • Degranulation and secretion of lysosomal enzymes.
  • Oxidative burst.
  • Modulation of adhesion molecule avidity.

⭐ IL-8 (CXCL8) is a potent chemokine primarily responsible for neutrophil chemotaxis and activation.

Phagocytosis - Engulf & Destroy

Crucial process where phagocytes (neutrophils, macrophages) engulf and destroy microbes & cellular debris.

• 1. Recognition & Attachment: (Opsonization)
  • Microbes bind phagocyte receptors.
  • Opsonins (e.g., IgG antibodies, C3b complement) coat targets, enhancing binding. 📌 IgG & C3b Grab Critters.
• 2. Engulfment: (Ingestion)
  • Pseudopods extend, forming phagosome (internalized vesicle).
• 3. Killing & Degradation: (Digestion)
  • Phagosome fuses with lysosome → phagolysosome.
  • Oxygen-Dependent (Respiratory Burst): Most potent.
    • NADPH oxidase: $O_2 + e^- \rightarrow O_2^{\cdot-}$ (Superoxide)
    • Superoxide Dismutase (SOD): $O_2^{\cdot-} + 2H^+ + e^- \rightarrow H_2O_2$ (Hydrogen Peroxide)
    • Myeloperoxidase (MPO): $H_2O_2 + Cl^- \rightarrow HOCl$ (Hypochlorite - bleach)

    ⭐ The microbicidal activity of the hydrogen peroxide-MPO-halide system is the most efficient bactericidal mechanism of neutrophils.

  • Oxygen-Independent:
    • Enzymes: Lysozyme, hydrolases.
    • Proteins: Lactoferrin, defensins.

, Engulfment (phagosome), Killing (phagolysosome, ROS, MPO))

Leukocyte Injury & Defects - When Cells Harm

• Activated leukocytes damage host tissues via:
  • Lysosomal enzymes
  • Reactive Oxygen Species (ROS)
  • Arachidonic Acid metabolites
• Contexts: Prolonged/inappropriate inflammation (autoimmunity), hypersensitivity.

Defects in Leukocyte Function

High‑Yield Points - ⚡ Biggest Takeaways

• Neutrophils are the primary cells in early acute inflammation.
• Extravasation steps: margination, rolling (selectins), firm adhesion (integrins like LFA-1/ICAM-1).
• Transmigration (diapedesis) across endothelium is mediated by PECAM-1 (CD31).
• Major chemotaxins: C5a, LTB4, IL-8 (CXCL8), and bacterial products.
• Phagocytosis includes opsonization (IgG, C3b), engulfment, and killing via ROS/lysosomal enzymes.
• Leukocyte Adhesion Deficiency (LAD) is due to defective integrins (CD18).
• Chédiak-Higashi syndrome shows impaired phagolysosome formation.