Second Line of Defense in Innate/Internal Defense System

Key Components

• Cells and Chemicals: The second line of defense predominantly involves cells and chemicals such as:
  • Phagocytic cells
  • Natural killer (NK) cells
  • Antimicrobial proteins
  • Fever
  • Inflammation

Pattern Recognition Receptors (PRRs)

• Toll-like Receptors (TLRs): Important in triggering immune response.
  • Recognize and bind to structures on microbes, disarming them before they cause harm.
  • Present not only on immune cells but also on epithelial cells.

Phagocytes

• Neutrophils:
  • Most abundant phagocytes.
  • Destroy themselves while fighting infection.
• Macrophages:
  • Develop from monocytes which leave bloodstream and enter tissues.
  • Classified into free (wander through tissues) and fixed macrophages (reside in specific organs).

Phagocytosis Process

1. Recognition and Adherence: Pathogens are recognized via their carbohydrate signatures.
2. Engulfment: Pathogen is engulfed into a phagosome.
3. Fusion with Lysosome: Phagosome fuses with lysosome, forming phagolysosome, digesting the pathogen.
4. Exocytosis: Indigestible material is exocytosed from the cell.

Natural Killer (NK) Cells

• Functions:
  • Large lymphocytes that patrol the blood and lymph.
  • Attack cells lacking "self" cell surface receptors.
  • Kill by inducing apoptosis (programmed cell death).
  • Secrete chemicals to enhance inflammation.

Inflammation

• Triggered by: Injury, heat, chemicals, infections.
• Benefits:
  • Prevents spread of damaging agents.
  • Disposes of debris/pathogens.
  • Alerts adaptive immune system.
  • Sets the stage for repair.
• Signs: Redness, heat, swelling, pain, and sometimes impaired function.

Stages of Inflammation

1. Chemical Release: Injured tissues release inflammatory chemicals (e.g., histamine).
2. Vasodilation and Increased Permeability: Causes local hyperemia (redness and heat) and exudate formation.
3. Phagocyte Mobilization:
   • Leukocytosis: Neutrophils released from bone marrow.
   • Margination: Neutrophils cling to capillary walls.
   • Diapedesis: Neutrophils squeeze through capillary walls.
   • Chemotaxis: Neutrophils follow chemical trail to site of injury.

Antimicrobial Proteins

• Interferons (IFNs):

  • Released by virus-infected cells.
  • Warn neighboring cells to block viral reproduction.
  • Types A and B activate NK cells; type G activates macrophages.

• Complement System:

  • Group of blood proteins that enhance immune response.
  • Pathways:
    1. Classical: Activated by antibodies.
    2. Lectin: Activated by lectins.
    3. Alternative: Activated spontaneously.
  • Functions: Enhance inflammation, promote phagocytosis, cause cell lysis.
  • C3 Split: Produces C3a (enhances inflammation) and C3b (opsonization and cell lysis).

Fever

• Caused by: Pyrogens acting on the hypothalamus.
• Benefits:
  • Increases metabolic rate.
  • Inhibits bacterial growth by sequestering iron and zinc.