Inf 2

• Types of leukocyte defects

  • Defect in adhesion
  • Defect in chemotaxis or phagocytosis
  • Defect in microbicidal activity
• Leukocyte adhesion defect-1


  Due to defect in integrin
• Leukocyte adhesion defect-2


  Due to defect in sialyl-Lewis X
• Chediak-Higashi syndrome


  Autosomal recessive disorder characterized by easy bruising, decreased phagocytosis and predisposition to recurrent bacterial infection
• Chronic granulomatous disease


  Defect in microbicidal activity
• Vascular changes in inflammation

  • Change in caliber
  • Increase permeability
• Arteriolar vasoconstriction


  Initial vascular change
• Arteriolar vasodilatation


  Subsequent vascular change
• Increased vascular permeability


  Hallmark of acute inflammation, results in exudate formation and increased blood viscosity
• Mechanisms of increased vascular permeability

  • Endothelial cell contraction
  • Cytoskeletal reorganization, Junctional retraction
  • Direct endothelial injury
  • Leukocyte-mediated endothelial injury
  • Increased transcytosis
  • Leakage from new blood vessels

  
• Edema


  Excess fluid in interstitial tissue or body cavities
• Transudate


  Extra vascular fluid with low protein content and specific gravity <1.012, essentially an ultrafiltrate of blood plasma
• Exudate


  Fluid rich in plasma proteins, fibrin, cells (neutrophils, macrophages, eosinophils, lymphocytes, RBCs) and debris, due to increased vascular permeability

  
• Functions of exudate


  • Dilutes toxins
  • Contains fibrin which localizes infection
  • Carries oxygen, nutrients to inflammatory cells
  • Carries drugs, antibodies against bacteria
• Leukocyte activation


  Series of WBC responses following binding of chemotactic factors to cell membrane, including secretion of mediators, degranulation, oxidative burst, arachidonic acid metabolism, increased adhesion molecules, and chemotaxis
• Leukocyte cellular events in acute inflammation


  • Margination (pavement) & rolling
  • Adhesion & transmigration
  • Chemotaxis & activation
  • Phagocytosis & degranulation
  • Release of leukocyte products
• Chemotaxis


  WBC locomotion towards site of injury along a chemical gradient due to action of chemotaxins
• Types of chemotaxins


  • Exogenous: bacterial products
  • Endogenous: C5a, LTB4, IL-8, PAF
• Steps of phagocytosis


  • Recognition & attachment
  • Engulfment
  • Killing or degradation
• Leukocyte products released


  • Lysosomal enzymes (protease)
  • Oxygen-derived active metabolites (free radicals)
  • Products of arachidonic acid metabolism
• Chemical mediators of inflammation

  Substances that play a role in genesis and modulation of inflammatory reaction, responsible for vasodilatation, increased permeability, and leukocyte emigration
• Types of chemical mediators

  • Vasoactive amines (histamine, serotonin)
  • Arachidonic acid metabolites (prostaglandins, leukotrienes)
  • Platelet-activating factor
  • Cytokines (IL-1, TNF, IL-6, IL-8)
  • Nitric oxide
  • Lysosomal constituents
  • Oxygen free radicals
  • Plasma proteases (complement, kinin, clotting, fibrinolytic systems)
• Microscopic appearance of acute inflammation includes congestion of blood vessels, exudation of fluid, and exudation of inflammatory cells mainly neutrophils
• Acute inflammation


  Initial reaction of vascularized tissue to injury, with neutrophils predominating in early stages and monocytes/macrophages in later stages
• Types of acute inflammation


  • Catarrhal
  • Serous
  • Suppurative (Purulent)
  • Fibrinous
• Morphologic patterns of acute inflammation


  • Serous inflammation
  • Fibrinous inflammation
  • Suppurative or purulent inflammation
• PAF means:


  Paroxysmal atrial fibrillation