Micro 1

Natural Defense of the Gastrointestinal Tract

  • The GI tract has a remarkable surface area of 400 m², which is 200 times that of the skin (only 2 m²).

  • Healthy large intestines host thousands of species of bacteria, known as commensal microorganisms or microbiome.

  • Symbiosis: A long-term association between different species, where at least one benefits.

Key Concepts

  • The GI tract needs constant protection from infectious and non-infectious threats introduced by food and water intake.

  • GI Disorders: Diarrheal diseases from enteric pathogens are a leading cause of childhood mortality and morbidity.

  • The gut's mucosal immune system must coexist with the microbiome while ensuring the epithelial layer is intact to prevent breaches.

Natural Defenses

1. Anatomical & Physiological Barriers

  • Skin (epithelium)

  • Oral mucosa

  • Intestinal epithelium: Cells joined by tight adhesion junctions and lined with a mucous membrane.

2. Chemical Barriers

  • Stomach acidity: Harsh for most microbes.

  • Complement and antimicrobial proteins:

    • Antibacterial enzymes (e.g. lysozymes, secretory phospholipase A2 from Paneth cells).

    • Antimicrobial peptides (e.g. defensins, cathelicidins, histatins).

    • Saliva enzymes support innate immunity.

    • Secretory IgA: The predominant antibody produced locally by plasma cells in mucosal walls, aids in immune responses.

Defense Mechanisms Against Pathogens

  1. First Line: Epithelium covering surfaces; can be breached and supplemented by mucosal immune defenses.

  2. Second Line: Various chemical systems (including the complement system) act as immediate antimicrobial barriers near the epithelium.

  3. If Breached: Innate lymphoid cells respond, followed by a slower response from adaptive immunity.

Immune Activation

  • Inflammatory inducers indicate pathogen presence or tissue damage:

    • PAMPs (Pathogen Associated Molecular Patterns) signal infections.

    • DAMPS (Damage Associated Molecular Patterns) signal tissue damage.

  • Sensor Cells: Express pattern recognition receptors (PRRs) to detect inducers, producing immune mediators.

Mucosal Immune System

  • The epithelial barrier: Most enzymatic food breakdown occurs in the small intestine.

  • Villi: Finger-like projections increase nutrient absorption area; covered by enterocytes (IEC).

  • Crypts of Lieberkuhn: House stem cells and secrete antimicrobial substances.

Peyer’s Patches

  • Located within the intestines: Contain microfold (M) cells for antigen presentation, increasing vulnerability to pathogens.

  • Intraepithelial Lymphocytes (IELs): Primarily T cells, involved in immune responses within the intestine.

Mucosal Immune System Interaction with Pathogens

  • The mucosa differentiates from systemic immunity, encountering various pathogens.

  • Mucosal surfaces protect through specialized structures and play an essential role in first-line defense against pathogens.

Gut-Associated Lymphoid Tissue (GALT)

  • GALT: Refers to gut-associated lymphoid tissues like tonsils, appendix, and Peyer’s patches that involve immune responses.

  • Mesenteric Lymph Nodes: Largest lymph nodes draining the gut, facilitating T and B cell antigen presentation for intestinal immune responses.

The Role of Mucus

  • Mucus creates a protective layer separating bacteria from epithelial cells, inhibiting inflammation and infection.

  • Goblet Cells: Secrete mucins and trap microbes and antibodies, vital for maintaining gut health.

Antigen Uptake and Presentation

  • M Cells: Transport antigens from the intestinal lumen to antigen-presenting cells (APCs).

  • Transcytosis: The process where antigens are carried across epithelial cells.

The Microbiome

  • Microbiome: Comprises bacteria, viruses, eukaryotes, and fungi that have a symbiotic relationship with the host.

  • Contains 10 trillion human cells and 100 trillion bacteria, predominantly found in the gut with varied species (Firmicutes, Bacteroides, etc.).

Functions of the Microbiota

  1. Microbial Antagonism: Competes for space and nutrients; produces inhibitory substances affecting pathogenic growth.

  2. Nutritional Benefits: Produces vitamins and aids food digestion.

  3. Enhancing Host Defenses: Essential for developing a healthy immune system.

Harmful Effects of Microbiota

  • Can become pathogenic if they move to sterile body parts or when the host becomes immunocompromised.

  • Dysbiosis: Microbial imbalance increases disease susceptibility, and antibiotic usage can lead to severe imbalances.

Hygiene Theory

  • Lack of microbial exposure in childhood leads to allergic diseases as the immune system fails to develop properly.

  • Increased instances of diseases like Crohn’s, asthma, and type 1 diabetes correlate with hygiene practices.

Conclusion and Quiz

  • Understanding the microbiome and its interface with our immune system is crucial for maintaining health and addressing diseases.

  • Final takeaway: The complexity and importance of the microbiota underscore its essential role in health and disease dynamics.