Non-Specific Defensive Factors of Oral Cavity

Non-Specific Defensive Factors of Oral Cavity

  • The decisive role in the protection of oral tissues from harmful microbial activities is played by saliva and epithelial cells of mucous membranes with their barrier function.

Non-Specific Defensive Factors of Oral Cavity

  • Continuous salivary flow washes out carbohydrates from dental surfaces. Salivary glands produce 0.5 to 3 litres of saliva per day. Saliva efficiently controls the supragingival environment and the same way prevents microbial entry into subgingival space.
  • The most powerful salivary bicarbonate buffer maintains the pH of the oral cavity within the range of 6.7-7.3. However, the diffusion of salivary components through dental plaque is slow; that’s why pH in the central part of dental plaque falls down to 5.0 or even less.
  • Oxidation-reduction or redox potential substantially influences the growth and reproduction of microbial populations and the rates of enzyme reactions in the oral cavity.
  • The levels of redox potential depend strongly on local concentrations of molecular oxygen.
  • Positive values of redox potential indicate aerobic conditions, negative – anaerobic ones. Saliva, tongue body, mucous epithelium of cheeks and palate have positive redox potential (+158-540 mВ), dental crevices and approximal dental surfaces display negative potential with its value about (–300 mВ).
  • The process of dental plaque maturation reduces local redox potential from about (+290 мВ) to (–140 мВ). This leads to the successful propagation of anaerobic bacteria.
  • Powerful innate immunity of the oral cavity is maintained by multiple humoral and cellular non-specific immune reactions.
  • The system of humoral non-specific defence factors encompasses mucins, glycoproteins, lactoferrin, lysozyme, peroxidase, short-chain basic defensive proteins histatins and cystatins. They are present in saliva and crevicular fluid in relatively large amounts.

Mucins

  • These are highly polymeric viscous glycoproteins secreted predominantly by submandibular and sublingual salivary glands. There are 2 major mucin glycoproteins in saliva – MG1 and MG2.
  • MG1 has a molecular weight of more than 1 mln Da. It tightly covers mucous membranes of the oral cavity. MG2 of molecular weight for about 125 kDa hinders aggregation and adhesion of oral streptococci.
  • Viscous mucin layer captures dental microflora thereby preventing bacterial penetration. Mucins also reduce acidic demineralization of hard dental tissues.
  • Likewise, other salivary glycoproteins block microbial adhesion to underlying oral mucous membranes.
  • Small cationic enzyme lysozyme (or muramidase) hydrolyses glycosidic bonds between N-acetyl-glucosamine and N-acetyl-muramic acid within bacterial cell wall peptidoglycan (or murein). It exerts easy lysis of bacterial cells.
  • Furthermore, lysozyme binds to monovalent anions, e.g., perchlorates, iodides, bromides, fluorides, thiocyanates, and some others, and at the same time, it binds to salivary proteases. This complex destabilizes the envelope of bacterial cells thus activating bacterial autolysins with subsequent cell lysis.

Lactoferrin

  • It is the iron-binding salivary glycoprotein that is synthesized by intercalated duct cells and granulocytes. Antimicrobial action of lactoferrin depends on its specific iron-binding capacity.
  • Under binding, it makes ferric ions unavailable for bacterial cells. Iron-deprived bacteria stop their growth and reproduction.
  • Iron-free lactoferrin or apolactoferrin demonstrates direct antibacterial effect agglutinating microorganisms that stimulate progression of caries and periodontitis (S. mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans).

Salivary peroxidase

  • It is secreted by acinar cells. It is a thermostable enzyme active in a broad pH range (3.0 to 7.0) and resistant to proteolysis.
  • It inactivates hydrogen peroxide generated by oral microflora and diminishes acid accumulation within dental plaque.
  • Peroxidase retains stability being absorbed on hard dental tissues, e.g., enamel. As a result, this enzyme slows down the progression of dental plaque, caries and periodontal diseases.

Histatins

  • These are low molecular weight (3 to 5 kDa) antimicrobial salivary peptides. They comprise the group of small basic peptides secreted by acinar cells, which are enriched with histidine.
  • Histatins block the growth of common oral pathogens (S. mutans, C. Albicans), aggregation of porphyromonads and streptococci.

Cystatins

  • It pertains to one more family of salivary antimicrobial peptides. They diffuse to saliva from gingival crevicular fluid.
  • Cystatins work as the inhibitors of bacterial thiol proteases thereby impairing normal microbial metabolism.
  • A substantial part of salivary antimicrobial defence is related to the complement system. Complement proteins leak from gingival capillaries into crevicular epithelial cells and reach gingival crevice. Then in smaller amounts, they may spread to saliva. This gradual overflow strongly accelerates in case of oral inflammation.

Complement proteins

  • It renders the variety of defensive reactions against the invaded pathogens: lysis of target cells (for instance, bacterial or viral-infected); production of chemoattractants and mediators that participate in inflammation and allergy, opsonization of bacteria and immune complexes for clearance by phagocytosis.
  • As in any body compartment, complement activation can take one of three pathways. The first is the classical pathway, which is initiated by specific antigen-antibody complexes. Lectin pathway closely resembles classical one except for the primary step: lectin pathway is stimulated by the reaction of host carbohydrate-binding proteins or lectins (e.g., human mannose-binding lectin) with bacterial polysaccharides.
  • The third route of complement activation is the alternative pathway that can be triggered by the components of bacterial cells, their endotoxins, host IgA molecules, some chemical substances, etc. Complement activation via this pathway is the most common in the oral cavity.
  • In all three pathways of complement activation, the resulting membrane-attack complex or MAC exerts the lysis of microbial cells. Nevertheless, general conditions for complement activation in the oral cavity are not so beneficial as in the bloodstream.