Non-Specific Barriers

(1) Skin is the first line of defense, a rugged impermeable barrier shown as a blue solid line. (See Epidermis Function)

(2) The circulatory system flushes the muscular and organelle tissue.

(3) Mucosal membranes regulate material transfers into and out of the body. These barriers are specialized to separate physiological functions, and are continuously flushed clean with mucopolysaccharides; noted purple.

(4) Barrier membranes incorporate tight junctions to rigorously regulate the select material transfers to provide tissue-specific protection, shown as green.

[These barriers are composed of epithelium and demarcated zones of immunity; for instance, inside vs. outside, mucosal vs. interstitial, exocrine (salivary and sebaceous glands), urogenital and kidney, respiratory region, synovia of articulating joints, blood-brain barrier, eye, germ line, and placenta. ]

1. Stratum corneum.
2. Tight junctions.
   1. Composed of epithelial proteins, occludins, claudins, and junctional adhesion molecules.
   2. Provides a tight seal at the blood-brain barrier.
   3. Provides a route for Langerhans cells to capture antigen.
   4. Intraepithelial T lymphocytes release IFN-δ, IL-4, and IL-10 to disrupt the junction.
   5. Antigen-driven tight junction diseases include:
      1. Skin: Pemphigus vulgaris, Pemphigus foliaceus
      2. GI/Mucosal: Inflammatory bowel disease, celiac disease, autoimmune bullous disease of oral mucosa, Crohn's disease and ulcerative colitis
   6. Mucous layer:
      1. Demarcation between tissues and systemic environment.
      2. Dynamic protection using viscous fluid flow mixed with a highly enriched mat of micro flora; for example, oral or enteric bacteria.
      3. Mucosal surface area: intestine approximately 300 m2, lung 70 m2, and total 400 m2.
      4. The acid mantle is a thin barrier to the penetration by bacteria and virus. Drastic pH alters the luminal environment from saliva pH of 6.2 to 7.4, Stomach pH of 1.5 to 3.5, small intestine at pH 6 for duodenum gradually increasing to pH 7.4 in the ileum, and large intestine ranging from 5.7 in caecum to pH 6.7 in the rectum.
      5. Intestinal mucosa is colonized by <1014 luminal bacteria from more than 500 species.
      6. The largest pool of macrophages located in the intestinal wall accompanied by NKT cells to manage bacterial stasis to the intestinal lumina.
      7. Approximately 70% of all lymphocytes are located within the lamina propria.

 

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