Kuliah 5

• Inflammation


  A response of vascularized tissues to infections and tissue damage that brings cells and molecules of host defense from the circulation to the sites where they are needed, to eliminate the offending agents
• Inflammation is a protective response that is essential for survival and part of innate immunity
• Classification of inflammation


  • Acute
  • Chronic
• Acute inflammation


  • Fast onset: minutes or hours
  • Mainly neutrophils
  • Usually mild and self-limited
• Chronic inflammation


  • Slow onset: days
  • Monocytes/macrophages and lymphocytes
  • May be severe and progressive
• Cardinal signs of acute inflammation

  • Heat (calor)
  • Redness (rubor)
  • Swelling (tumor)
  • Pain (dolor)
  • Loss of function (functio laesa)
• Heat (calor)


  Caused by vasodilation
• Redness (rubor)


  Caused by vasodilation
• Swelling (tumor)


  Caused by increased vascular permeability and edema
• Pain (dolor)


  Caused by physical and chemical stimulation of nociceptors
• Loss of function (functio laesa)

  Caused by pain, reflex muscle inhibition, and disruption of tissue structure
• Causes of inflammation


  • Infections (bacterial, viral, fungal, parasitic) and microbial toxins
  • Tissue necrosis (e.g., ischemia, trauma)
  • Foreign bodies (splinters, dirt, sutures)
  • Immune reactions (also called hypersensitivity)
• Inflammatory reaction


  1. Recognition of the injurious agent

  2. Recruitment of leukocytes

  3. Removal of the agent

  4. Regulation (control) of the response

  5. Resolution (repair)
• Acute inflammation: Vascular events

  • Vasodilation
  • Increased vascular permeability
• Vasodilation


  Caused by the primary mediator histamine released from mast cells
• Increased vascular permeability


  Caused by retraction of endothelial cells, induced by histamine and other mediators
• Acute inflammation: Cellular events

  • Leukocyte recruitment (rolling, integrin activation, stable adhesion, migration through endothelium)
  • Leukocyte activation (recognition, cytoskeletal changes, signal transduction, production of mediators, phagocytosis)
  • Phagocytosis (recognition and attachment, engulfment, killing and degradation)
• Acute inflammation: Mediators


  • Vasoactive amines (histamine, serotonin)
  • Arachidonic acid metabolites (prostaglandins, leukotrienes)
  • Cytokines (TNF, IL-1, IL-6, IL-17)
  • Chemokines
  • Complement system
  • Kinins (bradykinin)
  • Platelet-activating factor
• Mediators initiate and regulate inflammatory reactions
• Phagocytosis


  1. Recognition and attachment

  2. Engulfment

  3. Killing and degradation
• Phagocytic receptor


  Microbes bind to this on the phagocyte
• Phagosome


  Microbe ingested in this
• Lysosome


  Contains enzymes that fuse with phagosome
• Phagolysosome


  Phagosome fused with lysosome, where microbes are degraded
• Acute Inflammation: Mediators


  • Histamine
  • Prostaglandins
  • Leukotrienes
  • Cytokines (TNF, IL-1, IL-6, IL-17)
  • Chemokines
  • Platelet-activating factor
  • Complement
  • Kinins
• Vasoactive amines


  Histamine, serotonin
• Arachidonic acid metabolites


  Prostaglandins, leukotrienes
• Cytokines


  TNF, IL-1, IL-6
• Chemokines


  Attract and activate leukocytes
• Complement system


  Collection of soluble proteins and their membrane receptors that function in host defense and inflammation
• Kinins


  Bradykinin
• Histamine release


  From IgE-primed mast cells in response to an allergen
• Arachidonic acid


  • 20-carbon polyunsaturated fatty acid, most incorporated into membrane phospholipids
  • Mechanical, chemical, physical stimuli, other mediators trigger its release from membranes by activating cellular phospholipases, mainly phospholipase A2
  • Converted to bioactive mediators (eicosanoids)
• Cyclooxygenases


  Enzymes that convert arachidonic acid to prostaglandins
• Lipoxygenases


  Enzymes that convert arachidonic acid to leukotrienes and lipoxins
• Eicosanoids


  • Prostaglandins (PGI2, PGE, PGE2, PGD2)
  • Thromboxane A, leukotrienes C, D, E
  • Leukotriene B4
  • Prostaglandins PGC4, PGD4, PGE4
• COX-1 and COX-2


  Enzymes that catalyze prostaglandin synthesis
• Lipoxygenase


  Enzyme that catalyzes leukotriene synthesis
• Principal sources of cytokines

  • Macrophages, mast cells, T lymphocytes
  • Endothelial cells, blood vessels
  • Liver
• TNF


  Stimulates expression of endothelial adhesion molecules and secretion of other cytokines; has systemic effects