Lecture: Barrier Surfaces in the Innate Immune System

Overview

• Focus on structural, chemical, and biological barriers protecting internal tissues from external pathogens.
• Common features of barrier surfaces:
  • Epithelial Cells: Connected by tight junctions to prevent pathogen entry.
  • Distinct Microbiome: Composed of commensals (bacteria, viruses, and fungi) that prevent pathogen colonization and aid in various bodily functions like digestion and immune training.
  • Chemical and Protein Defense: Production of antimicrobial enzymes and peptides targeting pathogens.

Antimicrobial Peptides (AMPs)

• Defensins: Short peptides that disrupt pathogen membranes.
• Cathelicidins: Pro-peptides activated by cleavage; similar function to defensins.
• Histatins: Found in saliva, effective against pathogenic fungi.

Key Barrier Surfaces

Skin

• Largest organ with a large surface area requiring protection.
• Microbiome: Predominantly Gram-positive bacteria (Corynebacterium, Staphylococcus, Propionibacterium).
• Structure:
  • Stratum Corneum: Outermost dead cell layer, provides a harsh chemical environment.
  • Chemical Defenses: Includes urea, lactate, amino acids, fatty acids, and beta-defensins.
  • Langerhans Cells: Dendritic cells involved in immune response and tolerance to skin microbiome.

Respiratory Tract

• Large surface area inhaling a significant volume of air daily.
• Mucus Lining: Traps pathogens; "mucociliary escalator" moves them out of airways.
• Microbiome: Includes Moraxella, Dolosigranulum, Haemophilus, Streptococcus.
• Immune Cells: Alveolar macrophages and other resident cells manage homeostasis and infection.

Gastrointestinal Tract

• Begins with defenses in the mouth (saliva) and extends through the stomach and intestines.
• Mechanisms:
  • Peristalsis: Moves contents and prevents pathogen colonization.
  • Mucus Layer: Barrier and nutrient source for gut commensals.
• Microbiome Functions: Digestion, nutrient synthesis, immune system priming.
• Immune Defense: Rapid epithelial turnover and specialized cells (e.g., Paneth cells, M cells) for pathogen defense and immune activation.

Female Reproductive Tract

• Cervical Mucus: Traps pathogens.
• Vaginal Microbiome:
  • Dominated by Lactobacillus, which acidifies the environment.
  • Produces hydrogen peroxide to inhibit pathogenic growth.

Summary

• Barrier surfaces utilize:

  • Commensal Bacteria: Protective microbial layers.
  • Epithelial Barriers: Tight junctions and AMP production.
  • Chemical Defenses: Varied arsenal to inhibit pathogen entry.

• Next topic: The Complement System.