Provides optimal oral protection. The immune system of the oral mucosa. How to restore the immunity of the mucous membranes

The oral mucosa is a "shock" organ, the site of antigen-antibody reactions that can cause primary and secondary mucosal damage. In the system of "external barriers" the oral mucosa is the first line of defense of the body against a variety of pathogenic environmental factors.

The resistance of anatomical formations and the oral mucosa to damaging factors of microbial origin depends on the state of the defense 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. Insufficiency or perverse nature of protective reactions, combined with prolonged 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, periodontal disease and other diseases.

Specific antigens - substances of animal, plant and bacterial origin - found in saliva, tooth tissues, dental plaques, epithelium of the tongue and cheeks; ABO blood group antigens - in the epithelium of the cheeks, tongue, esophagus. The most significant part of antigens is the structure of a microorganism nature. Currently, hundreds of species 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 vital activity 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 provided by specific and non-specific mechanisms (it should be remembered that the definition of “non-specific” is rather arbitrary in immunology), and the latter in the oral cavity are more important than in many other organs. Initially, local immunity meant a complex of cellular and secretory nonspecific and specific reactions, including barrier functions of mucous membrane 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 now includes the total response of all cells of the lymphoid series that populate the mucous membranes, in cooperation with macrophages, neutrophilic and eosinophilic granulocytes, mast cells and other cells of the connective tissue and epithelium.

Nonspecificprotectioncavitiesmouth from cariogenic and other bacteria is primarily due to the antimicrobial properties of saliva containing 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 contained in it; 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, such as leukocytes, saliva and lacrimal fluid. Together with other components of saliva (for example, secretory immunoglobulin A - sIgA), it contributes to the destruction of microorganisms in the oral cavity, which makes it possible to limit their number. The important role of lysozyme in local immunity is evidenced by the increase in infectious and inflammatory processes that develop in the oral cavity with a decrease in its activity in saliva.

lactoferrin - an iron-containing transport protein capable of binding iron, making it unavailable for bacterial metabolism. Due to the competition with microorganisms for iron, their viability is limited, which is the manifestation of the bacteriostatic activity of lactoferrin. It is found in gingival sulcus secretions and locally secreted by polymorphonuclear neutrophils. Synergism in the protective action of lactoferrin with antibodies was noted. Its role in the local immunity of the oral cavity is clearly manifested in breastfeeding, when newborns receive high concentrations of this protein with mother's milk.

It also has similar protective properties. transferrin, also belonging to the group of siderophilins. It, like lactoferrin, limits the availability of iron to bacteria, 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 iron, which is necessary for microorganisms to synthesize cytochromes and other vital compounds.

lactoperoxidase - a thermostable enzyme that exhibits its bactericidal action 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 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, kamikrein).

The next protective factor in the oral cavity is proteins. complement systems. They acquire immunological activity under the influence of other immune factors, but 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 C3 fraction of the complement system is involved in the implementation of the effector functions of the activated complement system; it was found in the salivary glands.

Also to humoral factorsnon-specific protection of the oral cavity relate:

- interferons circulating in the blood - they increase the resistance of cells to the action of viruses, 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 tetrapeptide sialin, which neutralizes acidic products resulting from the vital activity of the microflora of dental plaques, as a result of which it has a strong anti-caries effect.

In nonspecific protection of the oral cavity, primarily from pathogens, not only humoral, but also cellular mechanisms are involved. 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 the saliva every minute, while 90% of all salivary leukocytes are 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 these cells are able to get into it from the gum 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 were 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. This may exacerbate the local inflammatory process caused by the aggressive influence of free radicals on the cell membranes of the gums and periodontium.

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

Specific oral protection It 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 various classes and other products of activated immunocompetent cells. A decisive role in providing 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 “normal” IgA dimer with a special protein, called the SC secretory complex, which is synthesized in epithelial cells. The IgA molecule enters the epithelial cell, where it combines with 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 the 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 birth. The sIgA concentration clearly increases in the early postnatal period. By the 6-7th day of life, the level of sIgA in saliva increases by almost 7 times. The 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 precursors of B-lymphocytes synthesizing 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 go beyond the Peyer's patches, followed by circulation and settlement in various mucous membranes and external secretion 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 some viral infections in the oral cavity (for example, herpes infection), sIgA antibodies also contribute to the elimination of the virus after its neutralization;

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

- 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 the tooth enamel, preventing the development of caries;

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

Due to the functions listed above, sIgA can be considered the leading factor in the first line of defense of the body against infectious and other foreign agents. Antibodies of this class prevent the occurrence of pathological processes on the mucous membrane without causing trauma. This is due to the fact that the interaction of sIgA antibodies with antigens, in contrast to the interaction of antibodies of the IgG and IgM classes with them, is not accompanied by the activation of the complement system (however, it should be borne in mind that sIgA in certain situations can activate the complement system through 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 that colonizes the surface of the oral mucosa. Thus, the level of this secretory immunoglobulin can be influenced by microbial proteases capable of cleaving it, such as, for example, the proteases secreted by Str.sangvis and Str.mutans.

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

It should also be noted a less noticeable, but rather important role of non-secretory IgA, which are produced by plasma cells and enter the site of the immune conflict with the blood flow, where they are included in the immune mechanisms of protection of the anatomical formations of the oral cavity.

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

Antibodies IgG and IgM provide complement activation 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 (C3v, C5b), and affect 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 their interaction with antigens, but they are able to have an important immunostimulatory 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 for phagocytosis.

Cellular immune response reactions in the oral cavity are carried out with the participation of CD3-lymphocytes (T-lymphocytes), among which are the so-called "regulatory" subpopulations of cells - CD4 and CD8 cells. The participation of T-lymphocytes in providing local immunity is largely due to the ability of these cells to secrete humoral factors that affect not only specific, but also non-specific defense reactions. So, for example, CD4 helper lymphocytes are a factor in specific cellular immunity and stimulate the activity of immunocompetent cells, but at the same time they also 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 local immune response stimulator that acts both on B lymphocytes (increases the secretion of immunoglobulins) and on CD4-lymphocytes, helpers and cytotoxins (enhances local cellular defense reactions). In addition, T-lymphocytes secrete lymphokines that are capable of:

- enhance the chemotaxis of polymorphonuclear leukocytes and monocytes,

- stimulate the differentiation of B-lymphocytes into plasma

- increase vascular permeability

- activate procollagenase,

- stimulate the activity of osteoclasts,

Lymphocytes related 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 responses.

CARIES

The modern polyetiological theory of the occurrence of caries takes into account many factors involved in the occurrence of this disease, among which there are general and local cariogenic factors. The general ones include: an inadequate diet and drinking water, somatic diseases, extreme effects on the body, inherited inferiority of the structure and chemical composition of tooth tissues, an unfavorable genetic code. Of the local cariogenic factors, the following are considered the most important: the microflora of the oral cavity, dental plaque and plaque, violations of the composition and properties of the oral fluid, carbohydrate food residues of the oral cavity, the state of the dental pulp and the state of the dentoalveolar system during the period of laying, 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, which produce acids in the process of life, and proteolytic, capable of producing enzymes. Since tooth enamel consists of an organic matrix impregnated with salts, acids contribute to the dissolution of the mineral component of tooth enamel, while enzymes destroy its organic substance. In the process of 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 in the oral cavity is inextricably linked with the pH value (pH) 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 the microflora of dental plaque is the activity of the microflora of the oral cavity and the influence of its metabolic products on the tooth tissue 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 in professional athletes - people with significant disorders of the immune system, which are caused by training loads, often exceeding the compensatory capabilities of the athlete's body. Shifts in the pH of the oral fluid to the acidic side correlate with the intensity of caries in athletes, and they are the greater, the higher the training loads, and the most acidic reaction of the oral fluid occurs at the peak of the training season.

Since the control over the vital activity of all microorganisms, their activity and reproduction is carried out by specific and non-specific 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 enamel of the teeth, the question arises about its immunological properties, as well as the possibility of the immune system responding to this type of tissue. Often, tooth enamel is referred to as the so-called "barrier" tissues, which have a relative immunological "privilege". These tissues, when damaged, lose their ability to reparative regeneration, which is also characteristic of 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 actually regeneration. In certain situations, for example, when an emulsion of tooth enamel is introduced into the body along with an adjuvant - a substance that stimulates an immune response - the immune system can interact with 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 have established that enamel immunogenic proteins are present both in newly formed enameloblasts and in 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 foregoing, tooth enamel should be regarded as a tissue that is not completely "beyond the barrier", but at the same time it is actually a barrier that ensures the relative isolation of the dentin layers from the effects of immune reactions.

Important, from the point of view of the formation of the microflora of the oral cavity, is plaque containing various microorganisms and immune components. With the use of carbohydrates and insufficient oral care, cariogenic microorganisms are tightly fixed on the pellicle, forming plaque. Sticky food and its remnants are able to harden in the retention points of the teeth (fissures, pits, contact surfaces, fillings, prostheses), where they undergo fermentation and decay.

Dental plaque contains, for example, streptococci Str. mutans, Str. Sanguis, Str. salivarius, which are characterized by anaerobic fermentation. Plaque microorganisms are able to fix and multiply on hard tooth tissues, metal, plastic. At the same time, they produce polysaccharides containing various carbohydrates, which in turn contribute to the development of the process of damage to tooth 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 tissues of the tooth under the influence of cariogenic microflora leads to the formation of a defect in the form of a cavity, which contributes to the penetration of microbes into the underlying layers and their destruction. The nature of the cariogenic microflora and the degree of contamination of dental plaque depend on the state and functionality of the body's defense mechanisms. For example, in immunodeficiency states in the plaque of patients, Str. Mutans, microorganisms of the genus Cabdida and Staphylococcus are more common. The immune components of plaque, in the formation of which one of the leading values belongs to saliva and the sIgA contained in it, include albumin, fibrinogen, immunoglobulins and other proteins. Along with sIgA, plaque includes serum immunoglobulins, in particular IgA, IgG, and sometimes small amounts of IgM. The total content of immunoglobulins in soft plaque is about 0.5% of the dry matter mass. Lysozyme, amylase, and sIgA enter plaque from saliva, and serum immunoglobulins from krevicular fluid.

sIgA antibodies certainly affect plaque formation: streptococci and other bacteria found in salivary sediment and plaque are coated with these immunoglobulins, which can be washed off the bacteria at low pH; they can also be associated with the protein components of the plaque, which have antigen properties. Bacteria in saliva and plaque are covered 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 plaque is an amorphous substance that adheres tightly to the surface of the tooth, and the accumulation of microbial waste products and mineral salts in plaque leads to its transformation into dental plaque.

dental plaques (supra- and subgingival) are accumulations of bacteria in the matrix of organic substances, mainly proteins and polysaccharides, brought there by saliva and produced by the microorganisms themselves. Under the plaque there is an accumulation of organic acids, which play the main 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 of the medium, however, actinomycetes are isolated from the plaques of both jaws with the same frequency. Analysis of the amino acid composition of the plaque showed that it contains small amounts of aspartic acid, serine, proline, glycine, cysteic acid, histidine, and arginine. In general, the pellicle of the tooth and the plaque contain the same protein components that have a protective effect.

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

Secretory immunoglobulin A (sIgA), which accounts for 85% of all immunoglobulins in saliva, is considered the most important of the specific factors protecting teeth, the level of which determines the risk of caries and the development of caries. Its activity in protecting teeth from caries is associated with the inhibition of the enzymatic activity of cariogenic streptococci and with the anti-adhesive activity of saliva and other antibacterial properties. sIgA most effectively manifests its capabilities when interacting with nonspecific protection factors, for example, complement and lysozyme, which is able to activate this immunoglobulin.

Lysozyme, the enzyme mentioned at the beginning of this section, is found in significant amounts in saliva. In the absence of lysozyme in saliva, a 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.

The so-called antibacterial factor of saliva is also referred to local protective factors that affect the occurrence and development of caries. In its presence, lactobacilli and streptococci lose their viability. In persons resistant to caries, the activity of the antibacterial factor of saliva is higher than in persons susceptible to this disease. Serum albumin is able to inhibit the activity of this salivary factor.

Literature data given by various researchers who studied the content of immunoglobulins in patients with caries are ambiguous. It contains indications that the concentration of IgA in the saliva of children with different intensity 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, a high level of IgA was detected. Other researchers noted that the titer of sIgA in saliva during the examination of patients with active caries was determined higher than in healthy individuals, and the degree of increase correlated with the degree of damage to the teeth by caries. Probably, these differences in the level of the indicator, determined by different authors, can be due to several reasons. For example, the fact that studies were conducted on clinically unequal groups did not always take into account the state of the immune system of patients, including its ability to form antibodies: it is known that IgA selective immunodeficiency is one of the most common disorders of immunity, as well as the use different methods for determining the concentration of immunoglobulin.

In addition to immunoglobulin A, immunoglobulins of other classes also participate in the protection of the oral cavity from infectious agents, and, therefore, in the pathogenesis of caries. For example, class G immunoglobulin, which enters the saliva with the krevicular 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-carious effect of IgG is manifested only with a deficiency in saliva of sIgA. 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 resistant to the disease.

Thus, we can conclude that the above information confirms the active participation of specific and nonspecific protective mechanisms in the development of caries. The opinion that one of the most important mechanisms for the onset and development of dental caries is associated with the suppression of the body's immunological reactivity has been expressed for a long time (for example, in 1976 by G. D. Ovrutsky et al.). Further studies have 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 organism and in violations of the immune system, which must be taken into account in the treatment of patients, including the necessary immunocorrective drugs in therapy.

For citation: Effective protection of the oral mucosa // RMJ. 2000. No. 1. S. 53

The mucous membrane of the oral cavity, populated by a variety of microorganisms, is the site of a delicate balance between the local bacterial flora and the body's defenses. With the weakening of the body's defenses due to excessive proliferation of bacteria or with a decrease in general and especially local immune defenses, the balance is disturbed, which contributes to the development of an infection focus in the oral mucosa. The mucous membrane of the mouth is extremely intensively supplied with blood, has a relatively large surface, therefore it forms an entrance gate for the penetration of infections into the body and serves as a place of colonization and infection by potentially pathogenic microorganisms in case of an overstrain of the body's natural defenses. The body's defenses include general and local factors. Local protection is provided by the integrity of the oral mucosa, the composition of saliva and lymphoid tissue. The integrity of the oral mucosa is the best guarantee of a good physiological barrier to infection. Due to the high content of immunoglobulins of the classes IgG, IgM and IgA, delivered along with the bloodstream or formed on the spot, the mucous membrane is involved in the creation of specific humoral immunity of the oral cavity. The protective factors of saliva are determined not only by its mechanical properties, but also depend on the biological compounds dissolved in it that can cause cell lysis. These substances include lysozyme, which has a bactericidal effect. In addition, saliva contains polymorphonuclear neutrophils, which have a high bactericidal activity against the microflora of the oral cavity. Finally, secretory IgA contained in saliva are a powerful local defense factor. The lymphoid tissue of the oral cavity includes: palatine, lingual and nasopharyngeal tonsils; lymphocytes and plasma cells of the salivary glands involved in the synthesis of secretory IgA; accumulations of lymphoid tissue on the gums; lymphoid cells of the lamina propria. Major inflammatory diseases of the oral cavity Gingivitis, periodontitis and stomatitis are among the most common diseases of the oral cavity. Gingivitis is an inflammatory disease of the gums characterized by hyperemia, swelling and bleeding of the gums with minimal trauma. The main cause of the disease is non-compliance with oral hygiene, resulting in the formation of dental plaque (colonies of microorganisms closely associated with the surface of the tooth). Local factors are also of considerable importance: incorrectly applied fillings and prostheses, mouth breathing, food debris, tartar. Gingivitis is common in systemic diseases, diabetes mellitus and other endocrine disorders, in adolescents and pregnant women. Without treatment, gingivitis often progresses to periodontitis. Periodontitis is an inflammatory disease of the tissues surrounding and supporting the teeth, progressing up to the destruction of the tissue of the interdental septa. Periodontitis develops under the influence of the same local and general factors as gingivitis. The advanced stages of the disease are characterized by tooth loss, with periodontitis considered to be the most common cause of tooth loss in adults. Stomatitis is an inflammatory disease of the oral mucosa. Stomatitis is often a sign of a systemic disease. Possible causes of stomatitis are infection, trauma, irritants and toxic substances, allergic and autoimmune diseases, beriberi, leukemia, and agranulocytosis. The main symptoms of the disease include hyperemia and swelling, itching, burning and dryness of the oral mucosa. Ulcerative stomatitis may be accompanied by halitosis and saliva mixed with blood. The persistence and recurrent nature of such inflammatory lesions requires not only the usual hygiene measures to care for the oral cavity and teeth, but also appropriate, reasonable therapy aimed at stimulating the protective forces of the oral mucosa. Therapy of inflammatory diseases of the oral mucosa In the light of the presented pathophysiological data, the immunological way of solving the problem allows us to propose a treatment that has two main effects - the treatment of active inflammatory diseases of the oral cavity and the prevention of its recurrence. One of the most effective drugs for the treatment of inflammatory lesions of the oral mucosa is the immunostimulant of biological origin Imudon. The drug is based on a polyvalent antigenic complex, which includes bacterial lysates of microorganisms that most often cause infectious processes in the oral cavity: Lactobacillus acidophilus, Lactobacillus fermentatum, Lactobacillus helveticus, Lactobacillus lactis, Streptococcus pyogenes, Streptococcus sanguis, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Corynebacterium pseudodiphteriticum, Fusiformis fusiformis, Candida albicans. Mechanisms of action and clinical efficacy of Imudon The main mechanisms of action of Imudon are: increased phagocytic activity due to the qualitative and quantitative improvement of phagocytosis; an increase in the content of lysozyme in saliva; stimulation and increase in the number of immunocompetent cells responsible for the production of antibodies; stimulation and increase in the amount of secretory immunoglobulins IgA; slowing down the oxidative metabolism of polymorphonuclear cells. Studies conducted by G. Jeanniard at the Laennec clinic (Paris) showed a significant increase in the content of lysozyme and immunoglobulins in saliva during treatment with Imudon (Table 1). In a recent study on the basis of the Department of Pediatric Therapeutic Dentistry of the Moscow State Medical University of Dentistry (Head of the Department - Prof. V.M. Elizarova), the effectiveness of Imudon therapy for acute herpetic stomatitis in 80 children aged 1 to 4.5 years was studied. Along with antiviral therapy, patients were prescribed Imudon 6-8 tablets for 5-7 days for mild disease, 8-10 days for moderate disease, 15 days for severe disease. Imudon reduced such clinical symptoms as pain and bleeding gums, in addition, there was a positive dynamics of lysozyme and secretory IgA in saliva (Table 2). The addition of Imudon to standard therapy reduced the time of epithelialization of herpetic elements and recovery (Table 2). Due to the pleasant mint taste, the children took it with pleasure, complications and side effects of the drug were not noted. Thus, due to the anti-inflammatory action and correction of local immunity, Imudon is highly effective in the treatment of acute herpetic stomatitis in children. At the Institute of Allergology and Clinical Immunology (Moscow), Imudon was studied in 88 patients with various diseases of the oral cavity (see Table 4). The clinical effect was manifested on the 3rd-4th day of taking the drug in the form of a decrease in inflammation and soreness of the oral mucosa. Clinical recovery occurred in 24% of patients, significant improvement and improvement - in 71%, the best results were obtained with stomatitis. Repeated courses of Imudon therapy for chronic diseases (recurrent oropharyngeal candidiasis, gingivitis) lengthened the remission period and reduced the number of relapses. The main indications for the appointment of Imudon: periodontitis; periodontal disease; gingivitis; stomatitis; glossitis; ulceration caused by dentures; infections after tooth extraction, implantation of artificial dental roots; pharyngitis, laryngitis; chronic tonsillitis. Dosage and method of administration of Imudon In acute inflammatory diseases of the oral cavity, Imudon is taken up to 8 tablets per day. The duration of the course of therapy is up to 10 days. In chronic diseases, the drug is prescribed 6 tablets for 20 days. It is recommended to carry out course therapy 2-3 times a year. The drug should be completely absorbed in the oral cavity, it is necessary to refrain from rinsing the mouth for 1 hour. Side effects and precautions when prescribing Imudon Cases of overdose and side effects when prescribing Imudon at recommended doses are not described. Imudon does not interact with other pharmacological drugs. It is possible to use the drug in women during pregnancy and lactation. When prescribing the drug to some patients with congestive heart failure, liver cirrhosis, etc., it should be borne in mind that one tablet of Imudon contains 15 mg of sodium. Conclusion Imudon is a highly effective and safe drug for the treatment of periodontal diseases and inflammatory diseases of the oral cavity. Imudon restores local mucosal immunity, alleviates the condition of patients and has a therapeutic and prophylactic effect.

THEIR ROLE IN THE PATHOGENESIS OF CARIES

Non-specific oral protection from cariogenic and other bacteria is primarily due to the antimicrobial properties of saliva containing 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 contained in it; 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, such as leukocytes, saliva and lacrimal fluid. Together with other components of saliva (for example, secretory immunoglobulin A - sIgA), it contributes to the destruction of microorganisms in the oral cavity, which makes it possible to limit their number. The important role of lysozyme in local immunity is evidenced by the increase in infectious and inflammatory processes that develop in the oral cavity with a decrease in its activity in saliva.

lactoferrin- an iron-containing transport protein capable of binding iron, making it unavailable for bacterial metabolism. Due to the competition with microorganisms for iron, their viability is limited, which is the manifestation of the bacteriostatic activity of lactoferrin. It is found in gingival sulcus secretions and locally secreted by polymorphonuclear neutrophils. Synergism in the protective action of lactoferrin with antibodies was noted. Its role in the local immunity of the oral cavity is clearly manifested in breastfeeding, when newborns receive high concentrations of this protein with mother's milk.

It also has similar protective properties. transferrin, also belonging to the group of siderophilins. It, like lactoferrin, limits the availability of iron to bacteria, 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 iron, which is necessary for microorganisms to synthesize cytochromes and other vital compounds.

lactoperoxidase- a thermostable enzyme that exhibits its bactericidal action 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 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, kamikrein ).

The next protective factor in the oral cavity is proteins. complement systems. They acquire immunological activity under the influence of other immune factors, but 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 C3 fraction of the complement system is involved in the implementation of the effector functions of the activated complement system; it was found in the salivary glands.

Also to humoral factors of nonspecific protection of the oral cavity relate: