Inflammation 2: Leukocyte Recruitment

Inflammation 2

• Leukocyte Recruitment and Activation

  • The series of events for leukocyte recruitment to extravascular space includes margination and rolling along vessel walls, firm adhesion to the endothelium, transmigration between endothelial cells, and migration through interstitial tissues toward a chemotactic stimulus
  • Adhesion is mediated by integrins interacting with their ligands on endothelial cells.
  • Specific ligands on endothelial cells are activated by TNF and IL-1
  • Integrins are low-affinity until activated, then cytoskeleton changes allow firm attachment

• Margination

  • The accumulation of leukocytes at the periphery of blood vessels
  • Rolling: Leukocytes weakly bind and detach from the endothelium, tumbling on the endothelial surface

• Rolling

  • Weak and transient interactions mediated by selectins (a family of adhesion molecules)
  • Types of selectins: E-selectin (on endothelial cells), P-selectin (on platelets and endothelium), and L-selectin (on leukocytes)

• Transmigration

  • Leukocytes migrate through the vessel wall by squeezing between cells at intercellular junctions (also called diapedesis)
  • Leukocyte migration is driven by chemokines, molecules produced in extravascular tissues.
  • Leukocytes secrete collagenases to pass through the vascular basement membrane

• Chemotaxis

  • Leukocytes move towards infection or injury sites along a chemical gradient
  • Chemotactic agents include bacterial products, pathogenic organisms, cytokines (especially chemokines), and complement system components (e.g., C5a) and leukotrienes from neutrophils

• Types of Emigrating Leukocytes

  • Cocci attract PMNLs
  • Bacilli attract monocytes
  • Viruses attract lymphocytes
  • Parasites and hypersensitivity attract eosinophils

• Phagocytosis and Clearance

  • Ingestion of particulate material by cells
  • Three steps: recognition and attachment of the particle, engulfment of the particle to form a phagocytic vacuole, and killing/degradation of the ingested particle
  • The most important phagocytes are neutrophils (microphages) and macrophages
  • Opsonization enhances phagocytosis

• Intracellular Destruction

  • Reactive oxygen species (ROS), Reactive nitrogen species (derived from nitric oxide), and Lysosomal enzymes (acid hydrolases and elastase)

• Neutrophil Extracellular Traps (NETs)

  • Extracellular fibrillar networks produced by neutrophils in response to infectious pathogens, inflammatory mediators

• NET Role

  • Traps provide high concentrations of antimicrobial substances at infection sites
  • Prevents spread of microbes by trapping them in fibrils
  • Formation involves nuclear chromatin and granule proteins, such as antimicrobial peptides and enzymes
  • Associated with sepsis

• Types of Acute Inflammation

  • Suppurative (Localized/Diffuse)
    • Abscess: Localized area of suppurative inflammation
    • Furuncle (boil) : Localized suppuration in hair follicle or sebaceous gland
    • Carbuncle (localized) : Suppuration in subcutaneous tissue, with multiple loculi and openings
    • Cellulitis (diffuse): Diffuse suppurative inflammation of subcutaneous tissue, often caused by strep infection.

• Types of Acute Inflammation(Continued)

  • Non-suppurative
    • Catarrhal: Mild inflammation of mucous membranes, characterized by exudate rich in mucus
    • Pseudo-membranous: Severe inflammation causing a membrane-like structure on mucous surfaces, often due to bacterial toxins
    • Serous: Inflammation characterized by exudation of watery fluid, rich in protein (e.g., pleural effusion, blisters)
    • Fibrinous: Inflammation marked by fibrin accumulation, often in body cavities (e.g., pericardium)
    • Hemorrhagic: Inflammation featuring blood in the exudate, often due to blood vessel damage
    • Allergic: Inflammation triggered by antigen-antibody reactions, characterized by exudate containing eosinophils (e.g., urticaria)

• Fate of Abscess

  • Rupture at point of least mechanical resistance if not drained
  • Healing by granulation tissue after evacuation/drainage

• Complications of Abscess

  • Ulcers, fistulas, and sinuses

• Spread of Infection

  • Lymphatic spread (lymphangitis, lymphadenitis)
  • Blood spread (toxemia, septicemia, pyaemia)

• Chronic Abscess

  • Failure of complete drainage