Cellular and humoral mechanisms of protection of the oral cavity. Effective protection of the oral mucosa

Nonspecific factors protecting the oral cavity from cariogenic and other bacteria include the antimicrobial properties of saliva and the barrier function of the cells of the mucous membrane and submucosal layer. Saliva is a liquid secretion produced by paired parotid, sublingual and submandibular glands, as well as small glands of the mucous membrane of the cheeks, tongue and lips. The composition of saliva varies from person to person and may vary depending on age, nutrition, state of the nervous system and other factors. It has a neutral or slightly alkaline reaction, rich in inorganic salts (chlorides, phosphates, bicarbonates and others) and organic protein substances (mucin, amylase, lysozyme and others). Per day, the salivary glands produce from 0.5 to 2.0 liters of saliva, which has pronounced bacteriostatic and bactericidal properties due to the humoral factors it contains: lysozyme, lactoferrin, lactoperoxidase, components of the complement system, immunoglobulins. Lysozyme- a mucolytic enzyme whose producers are mainly mononuclear phagocytes. Lysozyme is present in humans and animals in saliva and tear fluid. lymphoid tissue, breast milk and other secretions. It has a bacteriolytic effect on gram-positive bacteria due to the cleavage of glycosidic bonds of polymeric N-glucosamines that are part of bacterial cell walls. The culture of Micrococcus lysodellrticus is used as a test bacteria when studying the activity of lysozyme. Lysozyme consists of a polypeptide chain consisting of 129 amino acids, of which the C-terminal is leucine and the N-terminal is lysine. Its molecular weight is about 14,000 D. In the secretion of the parotid gland, the content of lysozyme is about 0.5 mg per 100 ml. Lysozyme can enter saliva, as well as blood serum and other liquids, either as a result of active secretion by mononuclear phagocytes, or as a result of the destruction of polymorphonuclear leukocytes depositing this enzyme. The pronounced antimicrobial activity of lysozyme ensures its participation in nonspecific protection. The important role of lysozyme in local immunity may be evidenced by an increase in infectious and inflammatory processes developing in the oral cavity with a decrease in its activity in saliva. In addition, lysozyme enhances phagocytosis and potentiates the lytic activity of the sIgA complex with the C3 fraction of complement against gram-negative bacteria (E. coli), Lactoferrin- an iron-containing transport protein, the bacteriostatic effect of which is associated with its ability to compete with bacteria for iron. Synergism between lactoferrin and antibodies has been noted. Its role in the local immunity of the oral cavity is most demonstrative in breastfeeding conditions, when newborns receive high concentrations of this protein in combination with secretory immunoglobulins (sIgA) with mother's milk. Lactoferrin is synthesized in granulocytes. Lactoperoxidase- a thermostable enzyme that, in combination with thiocyanate and hydrogen peroxide, exhibits a bactericidal effect. It is resistant to the action of digestive enzymes, active in a wide pH range from 3.0 to 7.0, and blocks the adhesion of S.mutans in the oral cavity. Lactoperoxidase has been detected in the saliva of children already in the first months of life. Fraction C3 The complement system has been detected in the salivary glands. It is synthesized and secreted by macrophages. Conditions for activation of the lytic action of the complement system on the mucous membranes of the oral cavity are less favorable than in the bloodstream. Aggregated sIgA can be activated and add complement via the alternative pathway via C3. IgG and IgM provide activation of complement along the classical pathway through the CIg - C3 - C5 - C9 membrane attack complex. Fraction C3 is involved in the implementation of the effector functions of the activated complement system. Saliva contains the tetrapeptide sialin. It contains glycyl - glycyl-lysine - arginine. Sialin is able to neutralize acidic products that are formed as a result of the vital activity of the microflora of dental plaques and, due to this, has a strong anti-caries effect. In the saliva of healthy people, polymorphonuclear leukocytes, monocytes, lymphocytes are always found, which enter it from the gingival pockets. In the local immunity of the oral cavity, connective tissue cells of the mucous membrane play an important role. The bulk of these cells are fibroblasts and tissue macrophages, which easily migrate to the site of inflammation. Phagocytosis on the surface of the mucous membrane and in the submucosa is carried out by phagocytic cells (granulocytes and macrophages). They help cleanse the outbreak from pathogenic bacteria. In addition, mast cells are located between the collagen fibers and around the vessels - potential participants in allergic reactions of the anaphylactic type. Plasma cells of connective tissue provide local synthesis of antibodies, mainly immunoglobulins of the sIgA class.

47 Specific factors for protecting the oral cavity
The last decade has been characterized by the rapid development of a new field of clinical immunology - oral immunology. This section is developed on the basis of the doctrine of local immunity of the mucous membranes of the mouth.
And the first theory of local immunity was formulated and theoretically substantiated by A. M. Bezredka in 1925. In his works, A. M. Bezredka emphasized the independence of local immunity from systemic immunity and the importance of local
immune mechanisms in the body's resistance to infection that enters the mucous membrane. However, for a long time it was continued to be believed that mucosal antibodies appear as a result of transudation of serum antibodies. And only in the 70s, works appeared in which it was shown that the so-called immunity of the mucous membranes is not a simple reflection of general immunity, but is due to the function of an independent system that has an important impact on the formation of general immunity and the course of the disease in the oral cavity.
Specific immunity is the ability of a macroorganism to selectively respond to incoming
his antigens. The main factor of specific antimicrobial protection is immune gamma globulins (immunoglobulins).
Immunoglobulins are protective proteins of blood serum or secretions that have the function of antibodies and belong to the globulin fraction. There are six classes of immunoglobulins: A, G, M, E, D, U. Of these classes, IgA, IgG, IgM are most widely represented in the oral cavity. It should be noted that the ratio of immunoglobulins in the oral cavity is different than in blood serum and exudates. If human serum contains mainly IgG, and IgM is contained in small quantities, then in saliva the level of IgA can be 100 times higher than the concentration of IgG. These data suggest that the main role in specific protection in saliva belongs to class A immunoglobulins. IgA is presented in the body in two varieties: serum and secretory. Serum IgA is not much different in structure from IgG and consists of two pairs of polypeptide chains connected by disulfide bonds. Secretory IgA is resistant to the action of various proteolytic enzymes. There is an assumption that enzyme-sensitive peptide bonds in secretory IgA molecules are closed due to the attachment of the secretory component. This resistance to proteolysis has important biological significance.
In the origin of secretory immunoglobulins, local synthesis plays a significant role. The correctness of this conclusion is confirmed by the differences in the structure and properties of serum and secretory IgA, the lack of correlation between the level of serum immunoglobulins and their content in secretions. In addition, isolated cases have been described when, when the production of serum IgA was impaired (for example, a sharp increase in its level in A-myeloma, disseminated lupus erythematosus), the level of IgA in the secretions remained normal.
Class A immunoglobulin is synthesized in plasma cells of the lamina propria and in the salivary glands. Of other immunoglobulins synthesized locally, IgM predominates over IgG (in serum the ratio is the opposite). There is a mechanism for selective transport of IgM across the epithelial barrier, therefore, with a deficiency of secretory IgA, the level of IgM in saliva increases. The level of IgG in saliva is low and does not change depending on the degree of IgA or IgM deficiency. In elucidating the question of the mechanism of secretory synthesis, studies using luminescent antisera were important. They made it possible to establish that IgA and the secretory component are synthesized in different cells: IgA - in the plasma cells of the lamina propria of the oral mucosa and other cavities of the body, and the secretory component - in epithelial cells. To enter secretions, IgA must overcome the dense epithelial layer lining the mucous membranes. Experiments with luminescent antiglobulin sera made it possible to trace the process of immunoglobulin secretion. It turned out that the IgA molecule can travel this path both through the intercellular spaces and through the cytoplasm of epithelial cells. Secretory IgA has pronounced bactericidal, antiviral and antitoxic properties, activates complement, stimulates phagocytosis, and plays a decisive role in the implementation of resistance to infection.
One of the important mechanisms of antibacterial protection of the oral cavity consists of preventing, with the help of IgA, the adhesion of bacteria to the surface of cells of the mucous membranes and tooth enamel. The justification for this assumption is that in the experiment, the addition of antiserum to S. mutans in a medium with sucrose prevented their fixation on a smooth surface. IgA was detected on the surface of bacteria using immunofluorescence. It follows from this that inhibition of bacterial fixation on the smooth surface of the tooth and the oral mucosa can be an important function of secretory IgA antibodies that prevent the occurrence of a pathological process (dental caries). Thus, secretory IgA protects the internal environment of the body from various agents that enter the mucous membranes.
Another way for immunoglobulins to appear in secretions is through their entry from blood serum: IgA enters saliva from serum as a result of transudation through an inflamed or damaged mucous membrane. The squamous epithelium lining the oral mucosa acts as a passive molecular sieve, particularly conducive to the penetration of IgG. Normally, this route of entry is limited. It has been established that serum IgM is least able to penetrate into saliva.
Factors that increase the entry of serum immunoglobulins into secretions are inflammatory processes of the oral mucosa, its trauma, local allergic reactions that occur when IgE antibodies (reagins) interact with the corresponding antigens. In such situations, the supply of a large amount of serum antibodies to the site of action of the antigen is a biologically appropriate mechanism for enhancing local immunity.

MECHANISMS OF ORAL IMMUNITY

1. The oral cavity is the “entry gate” for pathogens.

Along with food, breathing, and talking, a rich microflora enters the oral cavity, which may contain microorganisms of various pathogenicity. Thus, the oral cavity is the “gate of entry,” and its mucosa is one of the external barriers through which pathogenic agents can enter the body. Being an entry gate for many antigens and allergens, it is an arena for humoral and cellular immune reactions. These reactions entail primary and secondary damage. The most important property of this barrier is its structural integrity. Diseases of the oral mucosa occur much less frequently than might be expected. This is due, on the one hand, to the structural features of the mucous membrane: abundant blood supply, rich innervation. On the other hand, powerful mechanisms operate in the oral cavity that prevent the development of the inflammatory process. The oral cavity constantly contains substances of animal, plant and bacterial origin. They can be adsorbed on various parts of the mucosa and bind to specific antigens of the macroorganism, causing isoimmunization. Specific antigens are found in saliva, dental tissues, dental plaques, epithelium of the tongue and cheeks; blood group antigens ABO - in the epithelium of the cheeks, tongue, esophagus. The antigenic spectrum of normal oral mucosa is complex. It includes a set of species and organ-specific antigens. Significant differences have been identified in the antigenic structure of different parts of the oral mucosa: antigens are present in the soft palate, but absent in the mucous membrane of the hard palate, cheeks, tongue, and gums. The antigenic spectrum of normal oral mucosa is complex. It includes a set of species and organ-specific antigens. Significant differences have been identified in the antigenic structure of different parts of the oral mucosa: antigens are present in the soft palate, absent in the mucous membrane of the hard palate, cheeks, tongue, gums

2. Local immunity, its importance in maintaining internal homeostasis.

Local immunity (colonization resistance) is a complex set of protective devices of various natures, formed in the process of evolutionary development and providing protection for the mucous membranes of those organs that directly communicate with the external environment. Its main function is to maintain homeostasis of the internal environment of the macroorganism, i.e. it is the first barrier to the path of a microorganism and any antigen. The local protective system of the oral mucosa is composed of nonspecific protection factors and specific immune mechanisms; antibodies and T lymphocytes directed against a specific antigen.

3. Functions of oral secretion and its composition. Oral fluid (mixed saliva) consists of secretions secreted by the salivary glands and crevicular (cleft) gingival fluid, which makes up up to 0.5% of the volume of mixed saliva. This percentage may increase in patients with gingivitis. The protective factors of saliva are formed during active processes that occur locally. Mixed saliva has a whole range of functions: digestive, protective, trophic, buffer. Saliva has bacteriostatic and bactericidal properties due to the presence of various factors: lysozyme, lactoferrin, peroxidase, etc. The protective functions of saliva are determined by nonspecific factors and some indicators of specific immunity.

5. The importance of complement, kallikrein and leukocytes in maintaining colonization resistance of the oral cavity.

Complement is a complex multicomponent protein system, including 9 fractions. Only the S3 fraction of the complement system is found in saliva in small quantities. The rest are absent or detected in trace quantities. Its activation occurs only in the presence of inflammatory processes in the mucous membranes.

A very significant component of saliva are leukocytes, which come in large quantities from the gingival crevices and tonsils; moreover, 80% of their composition is represented by polymorphonuclear neutrophils and monocytes. Some of them, entering the oral cavity, die, releasing lysosomal enzymes (lysozyme, peroxidase, etc.), which help neutralize pathogenic and conditionally pathogenic flora. The remaining leukocytes in the mucosa, having phagocytic activity, create a powerful protective barrier against the development of the infectious process. Minor phagocytic activity is necessary and sufficient to capture food particles remaining in the oral cavity and microorganisms that have entered with them and thereby cleanse the oral cavity. At the same time, when foci of inflammation occur in the oral cavity, the local activity of salivary leukocytes can increase significantly, thus exerting a protective effect directed directly against the pathogen. Thus, it is known that phagocytes and the complement system are involved in protective mechanisms in diseases such as pulpitis and periodontitis.

Thromboplastin, identical to tissue, an antiheparin substance, factors included in the prothrombin complex, fibrinase, etc. were found in saliva. They play an important role in providing local

homeostasis, participating in the development of inflammatory and regenerative processes. In case of injuries, local allergic and inflammatory reactions, various classes of immunoglobulins are supplied from the serum, which supports local immunity.

6. Specific protective factors of saliva and mucous membrane.

A specific factor of antibacterial and antiviral protection are antibodies - immunoglobulins. The most significant in the specific immunity of the oral cavity from the known five classes of immunoglobulins (IgA, IgM, IgG, IgD, IgE) are class A antibodies, and in the secretory form (slgA). Secretory IgA, unlike serum IgA, is a dimer. It has two IgA monomer molecules connected by a J-chain and a glycoprotein SC (secretory component), which ensures slgA resistance to salivary proteolytic enzymes, as it blocks their points of application, shielding vulnerable areas. The leading role in the formation of sIgA is played by submucosal accumulations of lymphoid cells such as Peyer's patches, covered with a special cuboidal epithelium. It has been shown that sIgA and SC are present in the saliva of children from birth. The concentration of sIgA clearly increases in the early postnatal period. By 6-7 days of life, the level of sIgA in saliva increases almost 7 times. A normal level of sIgA synthesis is one of the conditions for sufficient resistance of children in the first months of life to infections affecting the oral mucosa. Factors that can stimulate the synthesis of slgA include lysozyme, vitamin A, and a complete balanced diet (vitamins, microelements, etc.).

IgG and IgA, penetrating from the bloodstream into the secretions of the oral cavity, are quickly inactivated by salivary proteases and, thus, are not able to perform their protective function, and antibodies of classes M, E and D are detected in small quantities. The IgE level reflects the allergic mood of the body, increasing mainly in allergic diseases.

The vast majority of plasma cells of the mucous membranes and all exocrine glands produce IgA, since T-helper cells predominate in the mucosal cells, which receive information for B lymphocytes intended for the synthesis of slgA. SC-glycoprotein is synthesized in the Golgi apparatus of epithelial cells of the mucous membrane of organs communicating with the external environment. On the basement membrane of these cells, the SC component binds to two IgA molecules. The J chain initiates the process of further migration, and the glycoprotein promotes the transport of antibodies through the layer of epithelial cells and the subsequent secretion of slgA to the mucosal surface. Secretory immunoglobulin A in the secretions of the oral cavity can be in free form (binds antigen with a Fab fragment) or be fixed

Secretory IgA has the following protective functions:

1) binds antigens and causes their lysis;

2) inhibits the adhesion of bacteria and viruses to the cells of the oral mucosa, which prevents the occurrence of the inflammatory process, as well as their adhesion to tooth enamel (i.e., it has an anti-caries effect)

3) prevents the penetration of allergens through the mucous membrane. slgA, associated with the mucosa, form immune complexes with the antigen, which are eliminated with the participation of macrophages.

Thanks to these functions, sIgA are the leading factors in the body's first line of defense against infectious and other foreign agents. Antibodies of this class prevent the occurrence of pathological processes on the mucous membrane without causing trauma to it.

The protective functions of sIgA imply that methods for creating local passive immunity, including against caries, are promising.

1.Physico-chemical: barrier function of the intact oral mucosa, washing function of saliva, cleansing the oral cavity during chewing, etc.

2. Proteins and peptides of saliva that have nonspecific protective properties (humoral factors). Their list is given below.

Lysozyme– a low-molecular protein, an enzyme that cleaves the b-1,4-glycosidic bond in glycosaminoglycans and polysaccharides of the cell membranes of microorganisms. In addition, it stimulates the phagocytic activity of leukocytes and participates in regeneration. Lysozyme is found not only in saliva, but also in other secretory fluids.

Salivary nucleases– RNase and DNase cause degradation of nucleic acids of viruses and bacteria, which plays a significant role in protecting the body from the penetration of infectious factors through the oral cavity.

Lactoferrin is a glycoprotein contained not only in saliva, but also in other secretions: colostrum, tears, etc. It binds the iron of bacteria and thereby disrupts the flow of redox processes in them, providing a bacteriostatic effect.

Hisstatins– polypeptides rich in histidine, 12 types of them are known. Hisstatins have antiviral, antibacterial and antifungal effects, and also participate in the formation of acquired dental pellicle.

Complement system proteins, which are present not only in saliva, but also in other biological fluids, activating phagocytosis, participate in the lysis of microbes and virus-infected cells.

salivary a-amylase not only participates in the digestion of food carbohydrates in the oral cavity, but is also capable of hydrolyzing polysaccharides in the cell membranes of some bacteria.

Proteinase inhibitors, found in saliva, also belong to nonspecific antimicrobial protection factors. In particular, a1-proteinase inhibitor, a2-macroglobulin, cystatins. a1-proteinase inhibitor is synthesized in the liver, enters saliva from blood serum, inhibits elastase, collagenase, plasmin, kallikrein, as well as microbial serine proteinases. a2-macroglobulin is also synthesized in the liver, enters saliva from blood plasma, forming inactive complexes with proteinases, and can also be in a free state. Cystatins are synthesized and secreted by the parotid and submandibular salivary glands. These are low-molecular acidic proteins that inhibit the activity of cysteine ​​proteinases, which include cathepsins D, B, H, L and others containing cysteine ​​SH groups in the active center. Cystatins also have adhesive properties, as they are similar to the primary structure of fibronectin and laminin. Cystatins and other proteinase inhibitors protect proteins of saliva and oral mucosa from breakdown by proteinases and have antimicrobial and antiviral effects. Kinins formed under the influence of salivary kallikrein have pronounced chemotactic activity. In addition to activating the migration of leukocytes to the site of inflammation, kinins also promote the migration of leukocytes by increasing the vascular permeability of oral tissues. Nonspecific antibacterial protection of the oral cavity is provided by enzymes released by migrated leukocytes and secreted by the salivary glands: lysozyme, RNase, DNAse, myeloperoxidase and others.

3. Cellular nonspecific factors of antimicrobial protection - cellular immunity , which includes leukocytes (granulocytes), in particular neutrophils or polymorphonuclear leukocytes (PMN), eosinophils and basophils, monocytes and their differentiation products - macrophages, NK cells (natural killer cells) - one of the types of lymphocytes, as well as mast cells. Neutrophils and macrophages can phagocytose bacteria and fungi. Mast cells participate in the development of the inflammatory response, releasing inflammatory mediators (histamine, serotonin, leukotrienes, etc.). Normal killer cells carry out immunological surveillance of tumor cells, detect them and destroy them.

Specific factors for protecting the oral cavity.

During its life, the body encounters many foreign agents, molecules and organisms. In response to this, the immune system creates specific (acquired) immunity - lymphocytic. It is characterized by the following fundamental properties: high specificity, the presence of immunological memory of the encountered agent, and the ability to distinguish “self” from “foreign.” Disturbances in the immunological system, leading to recognition of “one’s own” as “foreign”, can lead to the destruction of the body’s own molecules and the development of autoimmune diseases.

There are two types of specific immune response: humoral and cellular. Humoral is associated with the production of antibodies (immunoglobulins) - special proteins that circulate in the blood and other biological fluids of the body and are capable of specifically binding to foreign molecules. Immunoglobulins are synthesized by plasma cells, and information about the specificity of the synthesized immunoglobulin is obtained from the B lymphocyte. Binding with antibodies leads to inactivation of bacterial toxins and viruses, disruption of their ability to bind to receptors of target cells and exhibit their infectious and toxic effects. In addition, antibodies can interact with surface antigens of microorganisms, forming complexes with them, which then recognize and destroy phagocytes (immune phagocytosis). These complexes can also activate the complement system and other nonspecific defense factors that contribute to the destruction of microorganisms and infected cells.

There are 5 classes of immunoglobulins: A, D, E, G, M. Antibody molecules have the shape of the Latin letter Y with two antigen-binding sites. They consist of two light (L-chain) and two heavy (H-chain) polypeptide chains. H chains have a significantly higher molecular weight than L chains. All 4 polypeptide chains are connected by many non-covalent and four covalent (disulfide) bonds. Antibody molecules consist of two identical halves, each of which contains one light and one heavy polypeptide chain, the N-terminal sections of which form the antigen binding site.

Some immunoglobulin classes are divided into subclasses. In particular, the Ig A class is divided into Ig A 1 and Ig A 2 or secretory (IgA S). Ig A 1 enters saliva from blood serum. 90% of secretory immunoglobulin is produced by the parotid salivary glands, 10% by the submandibular glands. It protects the mucous membranes of the oral cavity from microbial and viral infection. Secretory immunoglobulin differs from other immunoglobulins in its higher molecular weight, which is due to the presence in its composition, in addition to the H- and L-polypeptide chains, of additional peptides: the Sp-secretory component, which is a glycoprotein, and the I-polypeptide chain. IgA S dimers are connected by an I-chain and an Sp-secretory component, which protect the secretory immunoglobulin from the destructive action of enzymes found in the secretions of the mucous membranes and saliva. Immunoglobulins D act as a receptor for antigen in the plasma membrane of the B lymphocyte.

Immunoglobulins G are the main class of immunoglobulins localized in the blood and saliva during the secondary immune response. Immunoglobulins E stimulate the release of histamine and serotonin by mast cells and basophils in the blood during inflammatory and allergic reactions.


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The oral mucosa is a “shock” organ, the site of antigen-antibody reactions that can cause primary and secondary damage to the mucosa. In the “external barrier” system, the oral mucosa represents the body’s first line of defense against a variety of pathogenic environmental factors.

The resistance of anatomical structures and the oral mucosa to damaging factors of microbial origin depends on the state of the protective systems. According to the concept of local immunity, mucous membranes, as covers facing the external environment, protect the internal environment of the body and maintain the constancy of the internal environment through the close interaction of an evolutionarily developed complex of nonspecific and specific defense mechanisms. The insufficiency or perverted nature of protective reactions in combination with long-term persistence of microbial associations in the oral cavity, causing damage to its tissues, can lead to the development of many pathological processes: caries, gingivitis, stomatitis, periodontopathies and other diseases.

Specific antigens - substances of animal, plant and bacterial origin - are found in saliva, dental tissues, dental plaques, epithelium of the tongue and cheeks; blood group antigens ABO - in the epithelium of the cheeks, tongue, esophagus. The most significant part of antigens are structures of microorganism nature. Currently, hundreds of types of microorganisms (bacteria, viruses, fungi and protozoa) are known that form the normal microflora of the oral cavity, which is largely influenced by the composition of food: for example, an increased amount of sucrose leads to an increase in the proportion of streptococci and lactobacilli in it. The breakdown of food products contributes to the accumulation of carbohydrates, amino acids, vitamins and other substances in saliva and gingival fluid, which create favorable conditions for the life of microorganisms that use them as nutrient substrates. In inflammatory processes in the oral cavity (caries, gingivitis, stomatitis and others), mixed infections caused by associations of bacteria, spirochetes, fungi, and viruses are more common.

The effectiveness of local protection against infectious agents is ensured by specific and nonspecific mechanisms (one should remember that the definition of “nonspecific” in immunology is rather conventional), and the latter are more important in the oral cavity than in many other organs. Initially, local immunity meant a complex of cellular and secretory nonspecific and specific reactions, including the barrier functions of mucosal cells, phagocytic activity of neutrophils and macrophages, T-cell immunity, antibodies, antimicrobial proteins of external secretions, enzyme inhibitors. Local immunity was not identified with secretory immunity, but the B-cell response of the lymphoid tissue of the mucous membranes with the participation of the glandular epithelium, which supplies the secretory component, was considered as its central link. Later, the concept of local immunity expanded and currently includes the totality of the response of all lymphoid cells populating the mucous membranes, in cooperation with macrophages, neutrophilic and eosinophilic granulocytes, mast cells and other cells of connective tissue and epithelium.

Nonspecificprotectioncavitiesmouth from cariogenic and other bacteria is primarily due to the antimicrobial properties of saliva, which contains humoral (soluble) factors, and the barrier function of the cells of the mucous membrane and submucosal layer, as well as cellular elements that have migrated into saliva. During the day, the salivary glands produce up to 2.0 liters of saliva, which has pronounced bacteriostatic and bactericidal properties due to the large number of soluble components it contains; The most important of them are the following:

Lysozyme – an enzyme that dissolves the cell walls of infectious microorganisms; has bactericidal activity and is present in many cells, tissues and secretory fluids of the human body, for example in leukocytes, saliva and tear fluid. Together with other components of saliva (for example, secretory immunoglobulin A - sIgA), it helps to destroy microorganisms in the oral cavity, which helps limit their number. The important role of lysozyme in local immunity is evidenced by the increase in infectious and inflammatory processes developing in the oral cavity with a decrease in its activity in saliva.

Lactoferrin – an iron-containing transport protein that can bind iron and make it unavailable for bacterial metabolism. Due to competition with microorganisms for iron, their viability is limited, which is where the bacteriostatic activity of lactoferrin manifests itself. It is found in gingival crevicular secretions and is secreted locally by polymorphonuclear neutrophils. Synergism in the protective effect of lactoferrin with antibodies was noted. Its role in the local immunity of the oral cavity is clearly demonstrated during breastfeeding, when newborns receive high concentrations of this protein in their mother’s milk.

Possesses similar protective properties transferrin, also belonging to the group of siderophilins. It, like lactoferrin, limits the availability of iron to bacteria by firmly binding this trace element. Therefore, these two compounds of the siderophilin group represent an independent system of natural immunity that reduces the virulence of pathogens by binding the iron necessary for microorganisms to synthesize cytochromes and other vital compounds.

Lactoperoxidase – a thermostable enzyme that exhibits its bactericidal effect in combination with thiocyanate and hydrogen peroxide. Resistant to the action of digestive enzymes, active in a wide pH range from 3.0 to 7.0. In the oral cavity it blocks the adhesion of S.mutans. Lactoperoxidase is found in the saliva of children from the first months of life.

Various enzymes , which are contained in saliva, can be produced both by the salivary glands and secreted by cells and/or microorganisms contained in saliva. The function of these enzymes is to participate in the local mechanism of cell lysis and protection against pathogens ( acid phosphatase, esterases, aldolase, glucuronidase, dehydrogenase, peroxidase, carbonic anhydrase, camicrein).

The next protective factor in the oral cavity is proteins complement systems. They acquire immunological activity under the influence of other immune factors, however, the conditions for activating the lytic action of the complement system on the mucous membranes of the mouth are less favorable than, for example, in the bloodstream. The S3 fraction of the complement system is involved in the implementation of the effector functions of the activated complement system; it has been identified in the salivary glands.

Also to humoral factorsnonspecific protection of the oral cavity relate:

– interferons circulating in the blood – they increase the resistance of cells to the action of viruses and prevent their reproduction in cells;

– C-reactive blood protein – forms complexes with infectious agents, thereby causing activation of the complement system, as well as some cells of the immune system (phagocytes and others).

– saliva contains the tetrapeptide sialin, which neutralizes acidic products formed as a result of the vital activity of the microflora of dental plaques, as a result of which it has a strong anti-caries effect.

Nonspecific protection of the oral cavity, primarily from pathogens, involves not only humoral but also cellular mechanisms. The cells that ensure their functioning are mainly polymorphonuclear neutrophils and macrophages (monocytes), and both types of cells are found in saliva. It is estimated that approximately 1 million leukocytes enter saliva every minute, with 90% of all salivary leukocytes being polymorphonuclear neutrophils. At the same time, not only polymorphonuclear leukocytes and monocytes, but also lymphocytes are always found in the saliva of healthy people; all of the listed cells are capable of entering it from the gingival pockets.

The effectiveness of the protective functions of macrophages and neutrophils (microphages) is ensured not only by their ability to directly destroy pathogens - phagocytosis, but also by a wide range of biologically active substances with bactericidal properties that these cells are able to synthesize.

For example, macrophages produce some factors that stimulate the inflammatory process or chemotaxis (interleukin-1, leukotrienes, free radicals, and others). Polymorphonuclear neutrophils trigger a chain of redox reactions (oxidative metabolism). Superoxide ions, hydroxide radicals and atomic oxygen are found in saliva, which are released by cells during immune conflicts and enter directly into the oral cavity, where they lead to the death of a foreign cell captured by phagocytes. In this case, the local inflammatory process caused by the aggressive influence of free radicals on the cell membranes of the gums and periodontium may worsen.

In the local immunity of the oral cavity, connective tissue cells of the mucous membrane also play a significant role. The bulk of these cells are fibroblasts and tissue macrophages, which easily migrate to the site of inflammation. Phagocytosis on the surface of the mucous membrane and in the submucosal connective tissue is carried out by granulocytes and macrophages, helping to clear them of pathogenic bacteria.

Specific oral protection is provided primarily by humoral factors - proteins that are secreted by cells of the immune system during its antigenic activation: interleukins, specific antibodies (immunoglobulins) of different classes and other products of activated immunocompetent cells. A decisive role in ensuring local immunity of the oral mucosa is played by class A antibodies (IgA), especially its secretory form - sIgA, which in healthy people is produced by plasma cells in the stroma of the salivary glands and mucous membranes. Secretory IgA can also be formed as a result of the association of the existing “regular” IgA dimer with a special protein called the secretory complex SC, which is synthesized in epithelial cells. The IgA molecule penetrates the epithelial cell, where it combines with the SC and emerges on the surface of the epithelial cover in the form of sIgA. Saliva contains much more sIgA than other immunoglobulins: for example, in saliva secreted by the parotid glands, the IgA/lgG ratio is 400 times higher than that in blood serum. It is known that sIgA and SC are present in the saliva of children from the moment of birth. The concentration of sIgA clearly increases in the early postnatal period. By 6-7 days of life, the level of sIgA in saliva increases almost 7 times. A normal level of sIgA synthesis is one of the conditions for sufficient resistance of children in the first months of life to infections affecting the oral mucosa.

The leading role in the formation of sIgA is played by submucosal accumulations of lymphoid cells such as Peyer's patches. Antigenic stimulation leads to the selection of clones of B-lymphocyte precursors that synthesize IgA. At the same time, this antigenic effect activates regulatory subpopulations of T cells that control the proliferation of B lymphocytes. Further, it is possible for B-lymphocytes to escape beyond Peyer's patches with subsequent circulation and dispersal into various mucous membranes and exocrine glands, including salivary ones.

Secretory IgA perform a wide variety of protective functions:

– inhibit the ability of viruses and bacteria to adhere to the surface of the epithelial layer, preventing pathogens from entering the body;

– neutralize viruses and prevent the development of certain viral infections in the oral cavity (for example, herpes infection), sIgA antibodies also contribute to the elimination of the virus after its neutralization;

– prevent the absorption of antigens and allergens through the mucous membranes;

– take part in the regulation of the immune response, enhancing the antibacterial activity of phagocytes;

– are able to suppress the adhesion of cariogenic streptococcus (s.mutans) to tooth enamel, preventing the development of caries;

– sIgA antibodies form immune complexes with foreign antigens and allergens that enter the oral mucosa, which, with the participation of nonspecific factors (macrophages and the complement system), are eliminated from the body. In individuals with sIgA deficiency, antigens can be adsorbed on the mucous membrane and enter the blood, which leads to allergization.

Thanks to the functions listed above, sIgA can be considered a leading factor in the body’s first line of defense against infectious and other foreign agents. Antibodies of this class prevent the occurrence of pathological processes on the mucous membrane without causing trauma to it. This is due to the fact that the interaction of sIgA antibodies with antigens, unlike the interaction of antibodies of the IgG and IgM classes with them, is not accompanied by activation of the complement system (however, it should be borne in mind that sIgA in certain situations can activate the complement system along an alternative pathway through the C3 component this system).

It should be noted that the effect of sIgA largely depends on the state of the microflora colonizing the surface of the oral mucosa. Thus, the level of this secretory immunoglobulin can be influenced by microbial proteases that can break it down, such as the proteases secreted by Str.sangvis and Str.mutans.

The effectiveness of the participation of sIgA in protecting the oral cavity and the content of antimicrobial substances in external secretions, such as the above-mentioned lactoferrin, lactoperoxidase, lysozyme, as well as other factors, in combination with which immunoglobulin performs its protective functions, influences.

It should also be noted that the less noticeable, but quite important role of non-secretory IgA, which is produced by plasma cells and enters the bloodstream at the site of the immune conflict, where they are included in the immune mechanisms of protection of the anatomical formations of the oral cavity.

Immunoglobulins of other classes contained in human blood serum perform their inherent functions when protecting the oral cavity. IgM and IgG enter the oral cavity through the bloodstream, but they can also be synthesized directly there by plasma cells after specific (antigenic) stimulation. Then they enter the site of the immune conflict - the mucous or submucosal layer, or other formations of the oral cavity.

IgG and IgM antibodies ensure the activation of complement along the classical pathway through its C1-C3-C5-C9 membrane attack complex. As a result of the reaction of these immunoglobulins with antigens, antigen-antibody complexes are formed, which are capable of activating the complement system. Its activation by the immune complex causes a cascade of protein interactions. Intermediate or final products of this interaction can increase vascular permeability (factor C1), cause chemotaxis of polymorphonuclear leukocytes, promote opsonization and phagocytosis of bacteria (S3b, C5b), and influence other protective factors in the oral cavity.

IgM is able to neutralize foreign particles, cause agglutination and cell lysis; It is believed that these immunoglobulins are less effective than IgG in interacting with antigens, but are capable of having an important immunostimulating effect on the local lymphatic system.

Immunoglobulins G not only activate the complement system, but also bind to certain cell surface antigens (opsonization), thereby making these cells more accessible to phagocytosis.

Cellular immune response reactions in the oral cavity are carried out with the participation of CD3 lymphocytes (T lymphocytes), among which the so-called “regulatory” subpopulations of cells – CD4 and CD8 cells – are distinguished. The participation of T lymphocytes in providing local immunity is largely due to the ability of these cells to secrete humoral factors that influence not only specific, but also nonspecific defense reactions. For example, CD4 helper lymphocytes are a factor of specific cellular immunity and stimulate the activity of immunocompetent cells, but at the same time they stimulate nonspecific immunity of the oral cavity, releasing a number of substances, the main of which are: interferon-gamma - an active inflammatory agent that promotes the formation of antigens on the membranes of the HLA system, necessary for the interaction of immunocompetent cells; Interleukin-2 is a stimulator of the local immune response, acting both on B lymphocytes (increases the secretion of immunoglobulins) and on CD4 helper lymphocytes and cytotoxins (strengthens local cellular defense reactions). In addition, T lymphocytes secrete lymphokines that can:

– enhance the chemotaxis of polymorphonuclear leukocytes and monocytes,

– stimulate the differentiation of B lymphocytes into plasma cells

– increase vascular permeability,

– activate procollagenase,

– stimulate the activity of osteoclasts,

Lymphocytes belonging to T-cytotoxic/suppressor cells (CD8-lymphocytes), being in the oral cavity, inhibit the activity of B- and T-lymphocytes and thereby prevent excessive immune reactions.

CARIES

The modern polyetiological theory of the occurrence of caries takes into account many factors involved in the occurrence of this disease, among which general and local cariogenic factors are distinguished. Common ones include: poor diet and drinking water, somatic diseases, extreme effects on the body, hereditarily caused inferiority of the structure and chemical composition of dental tissues, unfavorable genetic code. Among the local cariogenic factors, the following are considered the most important: oral microflora, dental plaque and plaque, disturbances in the composition and properties of oral fluid, carbohydrate food residues in the oral cavity, the condition of the dental pulp and the condition of the dental system during the formation, development and eruption of permanent teeth.

Microbiological studies have shown the greatest involvement in the development of caries of two types of bacteria that live in the oral cavity: acid-forming bacteria, which produce acids in the process of life, and proteolytic bacteria, capable of producing enzymes. Since tooth enamel consists of an organic matrix impregnated with salts, acids help dissolve the mineral component of tooth enamel, while enzymes destroy its organic substance. During the interaction of tooth proteins with food, carbohydrates and acids are again formed, which contribute to the further dissolution of the mineral base of the enamel. The activity of acid-producing microorganisms found in the oral cavity is inextricably linked with the pH value of the oral fluid. A visible demineralizing effect of enamel is observed at a pH below 5.7 on its surface. The most significant factor that destabilizes the pH value of the oral fluid and is associated with the vital activity of dental plaque microflora is the activity of the oral microflora and the influence of its metabolic products on tooth tissue that determines the possibility of the occurrence and development of caries. This is confirmed by the results of the study, which showed that the most pronounced shifts in the pH of the oral fluid are among professional athletes - individuals with significant disorders of the immune system, which are caused by training loads that often exceed the compensatory capabilities of the athlete's body. Shifts in the pH of oral fluid to the acidic side correlate with the intensity of caries in athletes and they are greater the higher the training load, and the most acidic reaction of the oral fluid occurs at the peak of the training season.

Since control over the vital activity of all microorganisms, their activity and reproduction is carried out by specific and nonspecific protective mechanisms, it is impossible to imagine the development of the carious process without the participation of these mechanisms and the immune system of the macroorganism in particular in the pathogenesis of caries. Since typical caries begins with damage to the tooth enamel, the question arises about its immunological properties, as well as the possibility of the immune system reacting to this type of tissue. Dental enamel is often referred to as the so-called “barrier” tissues, which have a relative immunological “privilege”. When damaged, these tissues lose their ability to reparatively regenerate, which is also typical for enamel. When it is damaged, regeneration does not occur, and the known effect of remineralization of the subsurface layer of enamel during initial caries or after damage to the surface by acids is not regeneration itself. In certain situations, for example, when an emulsion of tooth enamel is introduced into the body along with an adjuvant - a substance that stimulates the immune response - it is possible for the immune system to interact with the enamel in the form of an autoimmune reaction, that is, an aggressive immune response to this tissue of one’s own body.

Enamel proteins have immunogenic properties (first described in 1971 by G.Nikiforuk and M.Gruca); subsequent studies established that immunogenic enamel proteins are present in both newly formed enameloblasts and pre-enameloblasts. At the same time, the immunogenicity and specificity of proteins are preserved in the initial period of enamelogenesis until enamel mineralization; The immunogenicity of the proteins of the formed enamel cannot be considered proven. Apparently, taking into account the above, tooth enamel should be regarded as a tissue that is not fully “beyond the barrier”, but at the same time it is itself a barrier, ensuring relative isolation of dentin layers from the effects of immune reactions.

From the point of view of the formation of the microflora of the oral cavity, it is important plaque , containing various microorganisms and immune components. When consuming carbohydrates and insufficient oral care, cariogenic microorganisms become tightly attached to the pellicle, forming plaque. Sticky food and its remains can harden in the retention points of teeth (fissures, pits, contact surfaces, fillings, dentures), where they undergo fermentation and rotting.

Dental plaque contains, for example, streptococci Str. mutans, Str. Sanguis, Str. salivarius, which are characterized by anaerobic fermentation. Plaque microorganisms are capable of fixing and multiplying on the hard tissues of the tooth, metal, and plastic. At the same time, they produce polysaccharides containing various carbohydrates, which in turn contribute to the development of the process of damage to dental tissues: glycans (provide adhesion, adhesion of microbes to the tooth surface), levans (a source of energy and organic acids), dextrans (producers of organic acids), having a demineralizing effect on tooth enamel. Demineralization and destruction of hard tooth tissues under the influence of cariogenic microflora leads to the formation of a defect in the form of a cavity, which facilitates the penetration of microbes into the underlying layers and their destruction. The nature of cariogenic microflora and the degree of plaque contamination depend on the state and functionality of the body's defense mechanisms. For example, in immunodeficiency conditions, Str. Mutans, microorganisms of the genus Cabdida and Staphylococcus are more often found in the dental plaque of patients. The immune components of dental plaque, in the formation of which one of the leading roles belongs to saliva and the sIgA contained in it, include albumin, fibrinogen, immunoglobulins and other proteins. Along with sIgA, dental plaque includes serum immunoglobulins, in particular IgA, IgG, and sometimes small amounts of IgM. The total content of immunoglobulins in soft dental plaque is about 0.5% by weight of dry matter. Lysozyme, amylase and sIgA enter dental plaque from saliva, and serum immunoglobulins from crevicular fluid.

sIgA antibodies certainly influence the formation of dental plaque: streptococci and other bacteria contained in salivary sediment and dental plaque are coated with these immunoglobulins, which can be washed off the bacteria at low pH; they may also be associated with protein components of plaque that have antigen properties. Bacteria in saliva and plaque are coated not only with IgA, but also with albumin, amylase, and quite often with IgM. At the same time, the enzymatic activity of amylase and lysozyme in the plaque is preserved. Soft dental plaque is an amorphous substance that adheres tightly to the surface of the tooth, and the accumulation of waste products of microorganisms and mineral salts in the plaque leads to its transformation into dental plaque.

Dental plaques (supra- and subgingival) are accumulations of bacteria in a matrix of organic substances, mainly proteins and polysaccharides, brought there by saliva and produced by the microorganisms themselves. Under the dental plaque there is an accumulation of organic acids, which play a major role in the appearance of a demineralized area on the enamel - lactic, pyruvic, formic, butyric, propionic and others, which are products of the fermentation of sugars by bacteria.

The microflora of plaques on the teeth of the upper and lower jaws differs in composition, which is explained by different pH values, however, actinomycetes are isolated from plaques of both jaws with the same frequency. Analysis of the amino acid composition of the plaque showed that it contains small quantities of aspartic acid, serine, proline, glycine, cysteic acid, histidine and arginine. In general, the tooth pellicle and plaque contain the same protein components that have a protective effect.

As already indicated, the mechanisms of protection of teeth and soft tissues of the oral cavity are quite diverse and are based on both nonspecific and specific reactions. The peculiarity of oral cavity protection, in contrast to other formations of the human body, is that its effectiveness depends to a greater extent on the full functioning of nonspecific reactions, which is reflected at the beginning of this section.

The most important specific dental protection factor, the level of which determines the risk of the occurrence and development of caries, is considered to be secretory immunoglobulin A (sIgA), which accounts for 85% of the amount of all immunoglobulins in saliva. Its activity in protecting teeth from caries is associated with inhibition of the enzymatic activity of cariogenic streptococci and with the anti-adhesive activity of saliva and other antibacterial properties. sIgA exhibits its capabilities most effectively when interacting with nonspecific defense factors, for example, complement and lysozyme, which is capable of activating this immunoglobulin.

Lysozyme, the enzyme mentioned at the beginning of this section, is found in significant quantities in saliva. In the absence of lysozyme in saliva, the full implementation of the sIgA immune response is impossible; It was also noted that the activity of the carious process increases as the content of lysozyme in saliva decreases. However, the presence of a correlation between the nature of the course of dental caries and the titer of lysozyme in saliva is not confirmed by all researchers.

Local protective factors that influence the occurrence and development of caries include the so-called antibacterial factor of saliva. In its presence, lactobacilli and streptococci lose their viability. In individuals resistant to caries, the activity of the antibacterial factor in saliva is higher than in individuals susceptible to this disease. Serum albumin can inhibit the activity of this salivary factor.

The literature data cited by various researchers who studied the content of immunoglobulins in patients with caries is ambiguous. In it one can find indications that the concentration of IgA in the saliva of children with varying intensities of dental caries is reduced, and this local deficiency of immunoglobulin is the cause of the development of the disease; in individuals resistant to caries, high levels of IgA were detected. Other researchers noted that the sIgA titer in saliva when examining patients with active caries was determined to be higher than in healthy individuals, and the degree of increase correlated with the degree of dental caries damage. It is likely that these differences in the level of the indicator, determined by different authors, may be due to several reasons. For example, due to the fact that the studies were conducted on clinically unequal groups, the state of the patients’ immune system was not always taken into account, including its ability to form antibodies: it is known that selective immunodeficiency for IgA is one of the most common immune disorders, as well as the use different methods for determining immunoglobulin concentration.

In addition to immunoglobulin A, immunoglobulins of other classes also participate in protecting the oral cavity from infectious agents, and, therefore, in the pathogenesis of caries. For example, immunoglobulin class G, which enters saliva with crevicu- lar fluid. It was noted that the development of caries occurs against the background of a decrease in the content of IgG in saliva. However, some experts believe that the anti-caries effect of IgG manifests itself only when there is a deficiency of sIgA in saliva. The development of caries is also accompanied by a decrease in the concentration of IgM in the saliva of patients, while it may not be detected at all in the saliva of healthy individuals who are resistant to the disease.

Thus, we can conclude that the information provided confirms the active participation of specific and nonspecific protective mechanisms in the development of caries. The opinion that one of the most important mechanisms of the occurrence and development of dental caries is associated with the suppression of the immunological reactivity of the body was expressed quite a long time ago (for example, in 1976, G. D. Ovrutsky et al.). Further studies confirmed and detailed the role of violations of defense mechanisms in the pathogenesis of caries. The results of these studies proved that dental caries and especially its acute forms, as a rule, develop against the background of suppressed nonspecific reactivity of the body and with disturbances in the functioning of the immune system, which must be taken into account when treating patients, including the necessary immunocorrective drugs in therapy.


Nonspecific factors protecting the oral cavity from cariogenic and other bacteria are due to the antimicrobial properties of saliva and the barrier function of the cells of the mucous membrane and submucosal layer. Per day, the salivary glands produce from 0.5 to 2.0 liters of saliva, which has pronounced bacteriostatic and bactericidal properties due to the humoral factors it contains: lysozyme, lactoferrin, lactoperoxidase, components of the complement system, immunoglobulins. The important role of lysozyme in local immunity may be evidenced by the increased frequency of infectious and inflammatory processes developing in the oral cavity with a decrease in its activity in saliva.

Lactoferrin is an iron-containing transport protein, the bacteriostatic effect of which is associated with its ability to compete with bacteria for iron. Synergism between lactoferrin and antibodies has been noted. Its role in the local immunity of the oral cavity is clearly manifested in breastfeeding conditions, when newborns receive high concentrations of this protein in combination with secretory immunoglobulins (SlgA) in their mother's milk. Lactoferrin is synthesized in granulocytes.

Lactoperoxidase is a thermostable enzyme that, in combination with thiocyanate and hydrogen peroxide, exhibits a bactericidal effect. It is resistant to digestive enzymes and is active in a wide pH range from 3.0 to 7.0. In the oral cavity it blocks the adhesion of S. mutans. Lactoperoxidase is found in the saliva of children from the first months of life.

The S3 fraction of the complement system was detected in the salivary glands. It is synthesized and secreted by macrophages. Conditions for activating the lytic action of the complement system on the mucous membranes of the mouth are less favorable than in the bloodstream.

Aggregated SIgA can activate and add complement via the alternative pathway through the SZ. IgG and IgM ensure the activation of complement along the classical pathway through the C1 - C3 - C5 - C9 - membrane attack complex. The S3 fraction is involved in the implementation of the effector functions of the activated complement system.

Saliva contains the tetrapeptide sialin, which neutralizes acidic products formed as a result of the vital activity of the microflora of dental plaques, as a result of which it has a strong anti-caries effect. In the saliva of healthy people, polymorphonuclear leukocytes, monocytes, and lymphocytes are always found, which enter it from the gingival pockets.

In the local immunity of the oral cavity, connective tissue cells of the mucous membrane play an important role. The bulk of these cells are fibroblasts and tissue macrophages, which easily migrate to the site of inflammation. Phagocytosis on the surface of the mucous membrane and in the submucosal connective tissue is carried out by granulocytes and macrophages. They help cleanse the outbreak from pathogenic bacteria. In addition, mast cells are located between the collagen fibers around the vessels - potential participants in allergic reactions of the anaphylactic type. A decisive role in ensuring local immunity of the oral mucosa is played by class A antibodies, especially its secretory form, SlgA. In healthy people, in the stroma of all exocrine glands (including salivary glands) and mucous membranes communicating with the external environment, the vast majority of plasma cells produce IgA.

The internal and external secretions of the oral cavity differ in the content of immunoglobulins. Internal secretions are discharge from gingival pockets, in which the content of immunoglobulins is close to their concentration in blood serum. In external secretions, such as saliva, the amount of IgA significantly exceeds their concentration in blood serum, while the content of IgM, IgG and IgE in saliva and serum is approximately the same. Secretory immunoglobulin SlgA is more resistant to the action of proteolytic enzymes compared to serum IgA. It has been shown that SlgA is present in the saliva of children from the moment of birth; by the 6th - 7th day of life, its level in saliva increases almost 7 times. Normal synthesis of SlgA is one of the conditions for sufficient resistance of children in the first months of life to infections affecting the oral mucosa.

Secretory immunoglobulins SlgA may perform several protective functions. They inhibit the adhesion of bacteria, neutralize viruses and prevent the absorption of antigens (allergens) through the mucous membrane. For example, SlgA antibodies suppress the adhesion of the cariogenic streptococcus S. mutans to tooth enamel, which prevents the development of caries. A sufficient level of SlgA antibodies can apparently prevent the development of certain viral infections in the oral cavity, such as herpes infection. In individuals with SlgA deficiency, antigens are freely adsorbed on the oral mucosa and enter the blood, which can lead to severe allergization consequences. Antibodies of this class prevent the occurrence of pathological processes on the mucous membrane without causing its damage, since the interaction of SlgA antibodies with the antigen, unlike antibodies G and M, does not cause activation of the complement system. Among the nonspecific factors that can stimulate the synthesis of SlgA, vitamin A should also be noted.