L3 Intro to Inflammation

• Inflammation


  The response of vascularised living tissue to injury or irritation

  
• Causes of inflammation


  • Ischaemia
  • Trauma
  • Toxins
  • Infection
  • Extreme temperatures
  • Ionising radiation
• Steps of the stereotypical inflammatory response

  1. Recognition of the injurious agent

  2. Recruitment of leukocytes

  3. Removal of the agent

  4. Regulation (control) of the response

  5. Repair (resolution)

  
• Acute inflammation


  • Lasts minutes-days
  • Innate Immune system
• Chronic inflammation


  • Lasts days-weeks/longer
  • Adaptive immune system
• Acute inflammation


  The immediate and early response of living vascularised tissue to injury

  
• Acute inflammation


  • Relatively stereotyped
  • Delivers white blood cells to site of damage
  • Leads to healing
• Components of acute inflammation

  • Vascular
  • Cellular
• Inflammatory exudate


  Vascular (vasodilation, increased vascular permeability) + Cellular (emigration of WBCs)
• Recognition in acute inflammation

  1. Sentinel cells such as macrophages, dendritic cells and mast cells detect damage or microbes with receptors for conserved patterns associated with damaged tissues or bacterial products

  2. Recognition of injury/ pathogen results in the release of mediators (amines, cytokines) which have local effects on blood vessels

  
• Vascular response in acute inflammation

  1. Vasodilation of arterioles- mediated predominantly by local histamine release from pre-formed granules in mast cells and synthesis of prostaglandin

  2. Increased permeability – also via histamine and synthesis of bradykinin and leukotrienes

  3. Congestion and Stasis – facilitates leukocyte recruitment into tissues

  
• Prostaglandins


  Involved in pain, fever and inflammation. Inhibition of prostaglandin synthesis reduces vasodilation & WBC recruitment, has analgesic effect through reduced nerve sensitisation, and has antipyretic effects in the hypothalamus of the brain

  
• Vascular permeability


  Increases, leading to transudate giving way to exudate (protein-rich fluid), increasing interstitial osmotic pressure and decreasing intravascular osmotic pressure, contributing to oedema
• Types of inflammatory exudate

  • Serous
  • Fibrinous
  • Purulent (suppurative)
• Cytokines in acute inflammation

  • TNF, interleukin (IL)-1 and IL-6 have local and systemic effects that coordinate the inflammatory response

  
• Cytokines in acute inflammation

  Locally they enable endothelial activation and attract/activate recruited leukocytes. Systemically they induce fever, acute phase reactants, and increased leukocyte production

  
• Neutrophils


  • Characterise acute inflammation, dominating between 6-24 hours
  • Short-lived in tissues (2-3 days)
  • Nucleus gains constrictions as it matures (2-5 lobes)
• Leukocyte recruitment in acute inflammation

  1. Congestion and stasis results in leukocyte margination

  2. Rolling: Integrins on leukocytes interact with selectins on activated endothelial cells

  3. Stable adhesion occurs through interactions with adhesion molecules

  4. Transmigration or diapedesis through inter-endothelial gaps

  5. Chemoattractants facilitate migration via chemotactic gradient

  
• Neutrophils can control microbes through phagocytosis, secretion of lysosomal enzymes, and NETosis (release of nuclear chromatin/material which traps microbes)
• Abscess


  Localised accumulation of pus which contains neutrophils, bacteria and necrotic debris
• Concentrated accumulations of neutrophils (often walled off) which liquify surrounding tissue are called abscesses, these are less responsive to antibiotics and will likely require drainage