Inflammatory Response Lecture Notes

Definition of Inflammation

• Inflammation: A response to tissue damage that initiates vascular and cellular events for cleaning cellular debris and initiating repair.
  • Causes of inflammation include:
    • Physical trauma
    • Chemical trauma
    • Infectious microorganisms
    • Sunlight/burns

Case Study: Gram-Negative Bacteria

• Gram-negative bacteria: Characterized by a lipopolysaccharide layer which includes lipid A (endotoxin).
• Antigens: Molecules that are immunogenic (activate immune cells) and reactive (initiate antibody production).
  • Types of antigens: sugars, proteins, glycoproteins.
  • Incomplete antigens: Haptens (e.g., poison ivy) that become complete antigens upon binding to skin proteins.

Mechanism of Inflammation Initiation

1. Endotoxins released from bacteria damage tissue cells.
2. Mast cells in the area are activated:
   • Release substances (e.g., histamines, leukotrienes, prostaglandins).
   • Histamines increase vascular permeability and cause inflammation symptoms.
3. Phospholipase A2 converts damaged cell membrane phospholipids into arachidonic acid, leading to the production of leukotrienes and prostaglandins.

Cellular Events in Inflammation

• Increased vascular permeability leads to:
  • Edema (swelling) from fluid leakage.
• Signs of inflammation:
  • Swelling
  • Pain (due to pressure on nociceptors and bradykinins)
  • Heat
  • Redness
  • Joint immobility (in severe cases)

Vascular Responses

• Vasodilation: Blood vessel enlargement increases blood flow, causing heat and redness.
• Selectins: Molecules expressed on endothelial cells interact with circulating white blood cells (WBCs) for adhesion and movement toward infection sites.
  • Margination: WBCs slow down and roll along the endothelium due to selectin interactions.
  • Diapedesis: WBCs squeeze through endothelial cells to reach the site of infection.
  • Chemotaxis: WBCs follow chemical signals (e.g., cytokines) to the site of infection.

White Blood Cell Activity

• Macrophages and other WBCs arrive at the site to combat infection.
  • Secrete interleukin-1 and Tumor Necrosis Factor Alpha (TNF-α) which:
    • Activate endothelial cells to produce E-selectins (later in the inflammatory response).
    • Induce fever via effects on the hypothalamus.
    • Stimulate production of acute-phase reactant proteins (e.g., C-reactive protein).

Fever and its Effects

• Interleukin-1 and TNF-α lead to fever by acting on the hypothalamus:
  • Increases body temperature, inhibiting microorganism survival and enhancing metabolism for healing.
  • C-reactive protein: Used as a diagnostic marker for inflammation.

Leukocytosis

• Leukocytosis: Increase in WBC production in bone marrow initiated by interleukin-1 and TNF-α to respond to infection.

Summary of Inflammatory Response Events

1. Bacterial endotoxins damage tissue and activate mast cells.
2. Histamines and other mediators increase vascular permeability.
3. WBCs marginate, undergo diapedesis, and follow chemotactic signals to the infection site.
4. Macrophages release cytokines, inducing further inflammatory responses including fever and acute-phase proteins.

Conclusion

• Understanding the inflammatory response provides insight into how the body reacts to infection and injury.
• Next lecture will focus on phagocytosis and the role of white blood cells in this process.