Innate Immune Responses of Oral Cavity

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Innate Immune Responses of Oral Cavity

  • Primary cellular reactions of innate anti-bacterial immunity are generally based on phagocytosis and activity of phagocytic cells within the oral cavity.
  • The latter comprise the members of the mononuclear phagocyte system (blood monocytes and resident tissue macrophages) and granulocyte system (polymorphonuclear leukocytes – neutrophils, basophils, eosinophils).
  • The saliva of healthy individuals steadily contains cellular elements usually moved from gingival crevices and pockets.
  • Approximately 90% of the cells within gingival crevice pertain to polymorphonuclear leukocytes, 10% are mononuclear cells.
  • Mononuclear leukocytes encompass 60% of B cells, 20-30% of T cells and for about 10-15% of macrophages.
  • Granulocytes and macrophages of oral cavity engulf and then destroy the invaded bacterial pathogens.
  • Phagocytes migrate and accumulate within inflammatory focus under the action of versatile groups of chemokines both of host or microbial origin (IL 8 and other cytokines, С3а and С5а complement fragments or anaphylatoxins, bacterial peptidoglycan, teichoic acids, and many others).
  • Microbial killing depends on the vast number of bactericidal reactions generated by phagocytes.
  • The most potent microbicidal mechanism is known as respiratory burst resulting in large amounts of reactive oxygen species (ROS).
  • The main ROS agents are superoxide anion (O2-), hydroxyl radical (•OH) and hypochlorite (OCl-) that break down biopolymers of bacterial cells within phagosomes.
  • Digestion of bacteria is also supported by numerous antimicrobial peptides (defensins) and hydrolytic enzymes (cathepsins, elastase, lysozyme, and many others) produced by phagocytes.
  • In parallel to microbial digestion, macrophages and dendritic cells activate antigenic presentation and enhance secretion of pro-inflammatory cytokines (IL-1, IL-12, IL-18, α-TNF, etc.). This stimulates the differentiation of naive Th0 cells into Th1 generating a local inflammatory response in the oral cavity.
  • The inflammatory state can be profoundly aggravated in case of infection spread from primary oral site to regional lymph nodes and further to the bloodstream (systemic inflammatory response).
  • It is followed by macrophage stimulation with bacterial LPS (or bacterial endotoxin) via its binding to membrane CD14 receptor molecule. This leads to massive overproduction of pro-inflammatory cytokines resulting in fever, hypotension, and if not treated – to multiple organ dysfunction and toxic shock.
  • Viral infections of the oral cavity are controlled by another powerful mechanism of innate immunity – activation of natural killers or NK cells.
  • It is a rather small cell population containing the great number of granules in the cytoplasm. NK cells exert the lysis of virus-infected target cells regardless of their antigenic specificity (so-called non-immune cytolysis). In addition, natural killers can destroy some bacteria.
  • NK cells release a great variety of cytotoxic substances – perforin, β-tumour necrosis factor or lymphotoxin, some special cytotoxic enzymes, or granzymes that activate apoptosis. Also, they induce cell death activating apoptosis of target cells via CD95-Fas ligand interaction.
  • Overall, non-specific reactions of the innate immune response can efficiently eliminate most of the microbial invaders. But in situations of progressive oral infections, antigen-specific acquired immunity should be stimulated.

References

  1. https://pubmed.ncbi.nlm.nih.gov/12697091/
  2. https://www.immunology.org/public-information/bitesized-immunology/organs-and-tissues/immunity-in-the-oral-cavity