Role of the Normal Microbiota
The normal intestinal microbiota is a crucial component of the innate immune system 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 microbiota is mediated through the production of specific substances:
- Lactic and acetic acids.
- Antibiotics and bacteriocins.
In addition, the microbiota constantly primes the immune system. The main stimulators include bacterial short-chain fatty acids, as well as muramyl dipeptides and muramyl tripeptides (products of bacterial peptidoglycan cleavage by lysozyme).
Mucosal Defense Mechanisms
The GI mucosa forms a robust barrier against infections. The inner mucin layer creates a physical obstacle preventing direct contact between bacteria and epithelial cells.
Antimicrobial peptides and antibodies block pathogen adhesion to epithelial cells. The primary protective antibody is secretory IgA (sIgA). As it passes through epithelial cells, a secretory component is attached to the IgA molecule, protecting the antibody from degradation by digestive enzymes. In infants, lactoferrin found in breast milk serves as an additional protective factor.
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 dietary components and commensal microbiota, despite their high antigenic activity. Tolerance is maintained by regulatory T cells ($T_{Reg}$) and the blockade of signaling receptors specific for self-microbiota antigens. Breakdown 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 T-lymphocyte subpopulations ($T_H1$, $T_H2$, $T_H17$, $T_{Reg}$, and $\gamma\delta$ T cells). They maintain 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 immune reaction in the small intestine is triggered by the interaction of pathogens (especially gram-negative bacteria) with dendritic cells and epithelial cells.
- Activated dendritic cells release the cytokine IL-23.
- IL-23 stimulates NK cells, NKT cells, $\gamma\delta$ T cells, and T helper 17 ($T_H17$) cells.
- These cells begin producing 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.