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The essential functions of saliva are both enabling and protective. Saliva enables mastication and speech as it lubricates the oral structures during function. It also protects enamel from demineralizing and enables a stable ecology of oral organisms to live as commensals while excluding more overtly pathogenic bacteria.

Lubrication: Lubrication is provided by mucins (glycoproteins) which are selectively adsorbed to mucosa and enamel. On mucosa, they protect the tissues against drying, irritants, and bacterial enzymes. Together with the water content of saliva, glycoproteins provide lubrication for speech and mastication and preparation of a food bolus which can be readily swallowed. It appears to be the carbohydrate part of the glycoproteins, which is important for lubrication. (see Chapter 6.2 Glycoproteins)

Mechanical cleansing: The flow of saliva and subsequent intermittent swallowing provide a flushing system which removes food particles, bacteria, and desquamated cells from the mouth. The rate at which this removal occurs is referred to as the clearance rate. The more complete the fluid eliminated at each swallow, the more rapid will be the clearance of a substance from the mouth. Clearance will also depend on the flow rate of saliva; it is thus dramatically reduced during sleep (see Chapter 4.2.3 Rate of Flow of Saliva). The clinical importance of clearance lies in the rate of elimination of sucrose and fluorides from the oral cavity. A high rate of salivary clearance in individuals has been associated with a reduction in caries prevalence.

Fig. 4.2 Oral habitats sheltered from salivary flow become readily colonized by oral organisms. An SEM image of a buccal/lingual section of a maxillary premolar. A pit in the center of the central fissure is a secluded habitat for bacteria. The proximity of the base of the pit to the dentin is an important factor in the progress of dental caries (magnification × 500). D, dentin; E, enamel.

Fig. 4.3 SEM images of the surface of keratinized oral epithelium, the impact of a restoration. (a) The superficial squamous cells of the healthy epithelium of the hard palate have a pitted surface into which projections from the overlying cells interlock. The epithelial cells provide a habitat for oral organisms (arrows). (b) The palate of a complete denture was covering these epithelial cells. The surface microstructure has become altered, and there are large numbers and variety of oral organisms which have colonized this surface (magnification × 10,000).

Buffering capacity: Calcium apatite crystals on the enamel surface may become ionized and dissolve into the saliva, if the fluid environment drops below a pH of 5.3. Saliva contains buffers which tend to restore the pH to neutral or at least safer levels of acidity. The primary sources of the buffering capacity of saliva are bicarbonate ions (HCO₃⁻). The products of the acid–bicarbonate reaction are water and carbon dioxide. Phosphates, protein, and urea are buffers of lesser importance. Organisms which are able to metabolize urea may form ammonia (NH₃⁺) as an end product. This will raise the pH and tend to neutralize acids. The buffering capacity of saliva becomes greater as the flow of saliva increases.

Antisolubility: Calcium and phosphate ions in the saliva are supersaturated due to the presence of certain calcium-binding proteins (see Appendix D.1 Saturated Solutions). There is therefore little tendency for calcium ions from the enamel to leave the surface and enter an already saturated environment (▶ Fig. 4.5). The majority of salivary proteins (50–70%) are characterized by the frequency of the amino acid proline in their chain structure. Proline has a particular affinity for binding calcium. This accounts for the ability of PRPs to maintain a supersaturated solution of calcium in saliva. It also accounts for their ability to bind chemically onto the calcium in the hydroxyapatite of enamel during the formation of pellicle. The attachment of PRPs to enamel not only protects it from being dissolved by acids in the mouth, but in addition, it prevents the deposition of apatite crystal onto enamel. Without this function “secondary” crystal deposits would grow onto tooth surfaces. Crystal growth on enamel is not calculus, which is calcified plaque. The PRPs also bind selectively to microorganisms providing a chain which forms a link between organisms and tooth surfaces via the salivary pellicle. The PRPs cannot bind to organisms before they have been absorbed onto the hydroxyapatite of the enamel. Only then is a special sequence of amino acids revealed to which organisms can attach. The PRPs also bind onto some food proteins, in particular tannins, which would be otherwise be toxic.

Fig. 4.4 A diagrammatic representation of the role of salivary pellicle in adhesion of oral organisms. Calcium-binding phosphoproteins (yellow) bind onto calcium atoms of enamel. Larger glycoproteins bind to the smaller phosphoproteins to form a layer of salivary pellicle. Bacteria bind selectively to certain larger proline-rich proteins in pellicle.

Fig. 4.5 A diagrammatic representation of the effect of acidity on the degree of saturation of saliva and the dynamics of mineralization and demineralization. Saliva is a saturated solution of calcium and phosphate ions at a normal pH. If the solution becomes acid, the saliva is no longer saturated and hydroxyapatite ions dissolve (demineralize) and enter solution from the crystal. If the solution becomes alkali, saliva becomes saturated and ions precipitate (remineralize) back onto the crystal.

Antimicrobial peptides and proteins: Oral fluid has several components (about 45) which are antibacterial to a varying degree. Some of the proteins such as immunoglobulins (Igs), lactoferrin, and lysozyme are thought to have a role in defense although studies have not shown a correlation between the levels of salivary proteins and dental caries. The smaller peptides on the other hand do appear to have a more predictable defensive action on oral bacteria. These are collectively called antimicrobial peptides (AMP). They include defensins (alpha and beta), cathelicidin, and histatins. All are found in salivary gland and duct cells and in gingival crevicular fluid. Their sources in crevicular fluid are the neutrophils that migrate into the oral cavity. One of the AMPs, alpha defensin was found to be significantly lower in children with caries. This finding may lead to a useful measure of caries risk in children. The defensins and cathelicidins are broadly effective against oral microorganisms including Streptococcus mutans and Porphyromonas gingivalis, but it is difficult to generalize their antibacterial function. It is likely that they act synergistically with other antimicrobials. They also stimulate the acquired immune system and could enhance IgA production.

Lysozyme: Lysozyme is an enzyme present in saliva and tears. Its antibacterial effect is due to the splitting of a bond in the peptide chain of the cell wall of certain gram-positive organisms. The normal flora of the mouth seems to be little affected by lysozyme; it may be more important as a defense against exogenous (“foreign”) organisms.

Peroxidaze: Peroxidaze catalyzes the peroxidation of thiocyanate (SCN) to hypothiocyanite (OSCN) which inhibits bacteria metabolism. Peroxidaze is effective in even low concentrations when the pH of plaque decreases.

Lactoferrin: Lactoferrin is an iron-binding protein which inhibits the metabolism of some bacteria.

Immunoglobulins: A secretory component is added to immunoglobulins in the salivary glands, which activate its potential to neutralize bacteria in the oral cavity. These secretory immunoglobulin A (sIgA) do not operate as humeral antibodies, as they are not in a tissue fluid environment. They therefore cannot make a direct attack on an antigen causing agglutination, precipitation, neutralization, or lysis. Neither they can produce any amplification of the complement or anaphylactic system. Immunoglobulins appear to operate in the following ways:

• sIgA neutralizes viruses, and toxins, or enzymes produced by microorganisms. For example, sIgA is able to neutralize the enzyme glycosyltransferase which is necessary for S. mutans to synthesis extracellular polysaccharides.

• sIgA blocks the attachment sites for adhesion of bacteria to the mucosal surface. This blocking occurs in two ways: by covering the specific attachment sites on epithelial cells and by covering the part of the bacterial cell wall which is the active site for attachment. Some species of bacteria are more susceptible than others to the blocking effect of sIgA (▶ Fig. 4.6).

• sIgA also cause bacteria to clump together (agglutinate) which facilitates clearance.

• sIgA may bind to the active sites of food antigens thereby reducing the risk of developing an excessive immune response and allergy to certain foods.

The defense mechanism of sIgA is not as effective as might be expected. Certain bacteria (Streptococcus, Bacteroides, and Capnocytophaga species) produce proteases which split the dimer of sIgA into two ineffective parts. These IgA proteases do in turn elicit antibody production, but they are so weakly antigenic that the response is not effective. This may explain why Streptococcus sanguis and Streptococcus mitior are able to remain constant members of the oral cavity throughout life. If a patient is treated with immunosuppressive drugs (e.g., used in bone marrow transplants), the secretion of sIgA is reduced, and the oral flora may become invaded with organisms from the gut. The presence of large numbers of gut organisms in the oral cavity causes a mucositis which is difficult to control. This mucositis suggests a wider protective role of sIgA. sIgA may be most effective in controlling the population of exogenous organisms in the mouth (see Chapter 4.7.3 Antigen Tolerance).

Fig. 4.6 Diagrammatic representation of the action of sIgA on salivary organisms. (1) some organisms are unaffected by sIgA and adhere selectively to salivary pellicle, while others (2) adhere to oral mucosal surfaces. IgA causes clumping (3) of susceptible bacteria and blocks sites (4) of adhesion to other organisms. Some bacteria (5) are able to split the IgA dimer.