Notes on Innate Immunity

The Concept of Immunity

• Pathogens cause disease by:
  • Gaining access to the body
  • Attaching to host cells
  • Evading the immune system long enough to cause harm

Innate Immunity

• Defenses present from birth
• Always ready and rapidly responds
• Detects and eliminates pathogens without memory
• Divided into:
  • First line of defense
  • Second line of defense

First Line of Defense

• Physical Factors:
  • Barriers and processes to remove microbes
• Chemical Factors:
  • Substances that inhibit or kill microbes

Physical Factors

• Skin:
  • Two layers: epidermis (dry, keratinized, multiple packed layers, shedding removes microbes) and dermis (collagen for abrasion resistance)
  • Epidermal dendritic cells: Phagocytize pathogens
• Mucous Membranes:
  • Lines body cavities open to the environment; mucus traps microbes
  • Ciliary escalator: Transports trapped microbes away
• Other examples include tears, saliva, urine, and secretions that help remove microbes.

Chemical Factors

• Perspiration:
  • Salt inhibits pathogen growth
  • Contains antimicrobial peptides and lysozyme (destroys bacterial cell walls)
• Sebum:
  • Keeps skin pliable and lowers skin pH, inhibiting bacteria
• Other Secretions:
  • Low pH of gastric juices and vaginal secretions inhibit microbes.

Second Line of Defense

• Activated when pathogens penetrate barriers
• Composed of cells and antimicrobial chemicals
• Defense Components of Blood:
  • Plasma: Water with electrolytes, nutrients, proteins, & antibodies
  • Formed elements: Erythrocytes (carry gases), leukocytes (defense), and platelets (clotting).
  • Leukocytes:
    • Granulocytes (neutrophils, basophils, eosinophils)
    • Agranulocytes (lymphocytes, macrophages)

Toll-Like Receptors (TLRs)

• Found on white blood cells responding to pathogens
• Recognizes PAMPs (e.g., LPS, flagella)
• Activation triggers cytokine release that regulates immunity

Inflammation

• Triggered by chemicals, microbes, or injury
• Functions:
  • Destroy infectious agents
  • Confinement of infectious agents
  • Repair of damaged tissues
• Classic signs: redness, swelling, pain, heat

Phagocytosis

• Process performed by phagocytes to ingest microbes
• Steps include:
  1. Chemotaxis
  2. Adherence
  3. Ingestion
  4. Digestion (using toxic species & enzymes)
  5. Elimination (retaining antigens for adaptive response)

Fever

• Body temperature set at 37°C (hypothalamus)
• Pyrogens (endotoxins) cause increase in hypothalamic set point
• Effects of fever: Enhance immune response, inhibit growth of pathogens

Complement System

• Serum proteins that enhance immune response via lysis of foreign cells
• Activated via three pathways:
  • Classical (antibodies), Alternative (pathogen products), Lectin (microbial polysaccharides).

Interferons (IFNs)

• Released by infected cells to inhibit viral spread
• Type I (IFN-alpha, IFN-beta): Activate antiviral proteins in neighboring cells
• Type II (IFN-gamma): Enhance phagocytosis

Iron-Binding Mechanisms

• Transferrins bind serum iron, limiting its availability to pathogens
• Involves lactoferrin, ferritin, and hemoglobin in the body's defense against iron-dependent microorganisms.