Role of normal microflora
The normal intestinal microbiota is a crucial component of the innate immunity of the gastrointestinal tract. It provides colonization resistance, preventing pathogenic and putrefactive bacteria from establishing themselves in the gut through pronounced antagonism and high competitiveness.
The protective action of the microflora is realized through the production of specific substances:
- Lactic and acetic acids.
- Antibiotics and bacteriocins.
In addition, the microflora continuously keeps the immune system in a primed state. The main stimulators are short-chain fatty acids of bacterial origin, as well as muramyl di- and muramyl tripeptides (products of bacterial peptidoglycan cleavage by lysozyme).
Mechanisms of mucosal defense
The GI mucosa forms a reliable barrier against infections. The inner mucin layer creates a physical obstacle preventing direct contact between bacteria and epithelial cells.
Antimicrobial peptides and antibodies block the attachment (adhesion) of pathogens to epithelial cells. The main protective antibody is secretory IgA (sIgA). Upon passing through epithelial cells, a secretory component is attached to the IgA molecule, which protects the antibody from degradation by digestive enzymes. In infants, an additional protective factor is lactoferrin found in breast milk.
Oral tolerance and immune cells
A vital property of GI immunity is the phenomenon of oral tolerance. This is the absence of an inflammatory response to food components and normal microflora (commensals), despite their high antigenic activity. Tolerance is maintained by regulatory T cells ($T_{Reg}$) and the blockade of signaling receptors for endogenous microbiota antigens. Disruption of this mechanism leads to pathologies such as Crohn's disease, chronic gastritis, and ulcerative colitis.
A variety of immune cells operate within the intestinal mucosa: macrophages, dendritic cells, NK cells, mast cells, and various subpopulations of T lymphocytes ($T_H1$, $T_H2$, $T_H17$, $T_{Reg}$, $\gamma\delta$ T cells). They maintain the physiological balance and suppress inflammation. In Peyer's patches, B lymphocytes differentiate into plasma cells that produce IgA and IgE.
Immune response in the small intestine
The initiation of an immune reaction in the small intestine begins with the interaction of pathogens (especially Gram-negative bacteria) with dendritic cells and epithelial cells.
- Activated dendritic cells secrete the cytokine IL-23.
- IL-23 stimulates NK cells, NKT cells, $\gamma\delta$ T cells, and type 17 T helper cells ($T_H17$).
- These cells begin to produce protective interleukins — IL-17 and IL-22, which act on the intestinal epithelium.
- As a result, the epithelium secretes chemokines (CXC, G-CSF) to recruit neutrophils and synthesizes antimicrobial peptides: lipocalin-2, $\beta$-defensins, calprotectin, and Reg3 lectin.
Briefly: answers to topical questions
What humoral factors of non-specific defense are present in saliva and gastric juice?
Saliva and gastric juice contain the following humoral factors of non-specific defense:
- Lysozyme — exhibits bactericidal activity by destroying the cell wall of bacteria in the oral cavity.
- Mucin — a glycoprotein that gives saliva its viscosity and forms a protective mucous component.
- Hydrochloric acid (HCl) — provides the bactericidal action of gastric juice by creating a low pH, which is detrimental to most microorganisms.
- Pepsinogen — together with hydrochloric acid, participates in creating an unfavorable environment for bacteria in the stomach, which functions as a "sterilization chamber".
Class and exam questions
What is the essence of colonization resistance?
This is the ability of the normal microflora to compete for habitat and prevent the colonization of the intestine by pathogenic and putrefactive bacteria.
Why does the secretory component attach to the IgA molecule?
The secretory component protects the antibody molecule from digestion by gastrointestinal enzymes, allowing sIgA to function effectively on the mucosal surface.
What role does IL-23 play in the intestine?
IL-23, secreted by activated dendritic cells, stimulates various populations of T lymphocytes and NK cells to produce the protective cytokines IL-17 and IL-22.
What else to study on this topic
- Mechanisms of formation and maintenance of oral tolerance
- The process of B lymphocyte differentiation in Peyer's patches
- The effect of short-chain fatty acids on the immune system
- Properties and functions of GI epithelial antimicrobial peptides
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