Nonspecific oral defense factors. The immune system of the oral mucosa

Nonspecific oral defense factors against cariogenic and other bacteria include the antimicrobial properties of saliva and the barrier function of mucosal and submucosal cells. Saliva is a liquid secret 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 different people and may vary depending on age, nutrition, condition nervous system and other factors. It has a neutral or slightly alkaline reaction, rich in inorganic salts (chlorides, phosphates, bicarbonates, and others) and organic substances of a protein nature (mucin, amylase, lysozyme, and others). During the 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, lacrimal fluid. lymphoid tissue, mother's milk and other secrets. It has a bacteriolytic effect on gram-positive bacteria by cleaving the glycosidic bonds of polymeric N-glucosamines that are part of the bacterial cell walls. Micrococcus lysodellrticus culture is used as test bacteria in the study of lysozyme activity. Lysozyme consists of a polypeptide chain of 129 amino acids, of which the C-terminal is leucine and the N-terminal is lysine. Its molecular weight is about 14000 D. Secret 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 fluids, 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 complement fraction 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 of lactoferrin with antibodies was noted. Its role in the local immunity of the oral cavity is most demonstrative in conditions breastfeeding when newborns receive high concentrations of this bulk in combination with secretory immunoglobulins (sIgA) with mother's milk. Lactoferrin is synthesized in granulocytes. lactoperoxidase- a thermostable enzyme, which, 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 was found in the saliva of children already in the first months of life. Fraction C3 complement systems were found in the salivary glands. It is synthesized and secreted by macrophages. The 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 become activated and add complement via an alternative pathway through C3. IgG and IgM provide complement activation 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 sialin tetrapeptide. It contains glycyl - glycyl-lysine - arginine. Sialin it 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 it has a strong anti-caries effect. In the local immunity of the oral cavity, cells of the connective tissue of the mucous membrane play an important 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 submucosa is carried out by phagocytic cells (granulocytes and macrophages). They contribute to the cleansing of the hearth 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. Connective tissue plasma cells provide local synthesis of antibodies, mainly immunoglobulins of the sIgA class.

47 Specific oral protection factors
The last decade is 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 continued to believe that mucosal antibodies appear due to extravasation of serum antibodies. And only in the 70s, works appeared that showed that the so-called mucosal immunity is not a simple reflection of general immunity, but is due to the function of an independent system that has an important effect 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
its antigens. The main factor of specific antimicrobial protection are immune gamma globulins (immunoglobulins).
Immunoglobulins are protective proteins of blood serum or secretions that have the function of antibodies and are related to the globulin fraction. There are b 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 in human serum IgG is mainly represented, and IgM is contained in a small amount, 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 represented in the body by two varieties: serum and secretory. Serum IgA differs little from IgG in its structure and consists of two pairs of polypeptide chains connected by disulfide bonds. Secretory IgA is resistant to various proteolytic enzymes. There is an assumption that enzyme-sensitive peptide bonds in secretory IgA molecules are closed due to the addition of a secretory component. This resistance to proteolysis is of great biological importance.
Local synthesis plays a significant role in the origin of secretory immunoglobulins. 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 secrets. In addition, isolated cases are described when, in case of impaired production of serum IgA (for example, a sharp increase in its level in A-myeloma, disseminated lupus erythematosus), the level of IgA in secrets remained normal.
Class A immunoglobulin is synthesized in the plasma cells of the lamina propria and in the salivary glands. Of other immunoglobulins synthesized locally, IgM predominates over IgG (the ratio is reversed in serum). There is a mechanism of selective transport of IgM through 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 deficiency of IgA or IgM. In elucidating the question of the mechanism of secretory synthesis, studies using luminescent antisera were of great importance. They made it possible to establish that IgA and the secretory component are synthesized in different cells: IgA - in plasma cells of the lamina propria of the oral mucosa and other body cavities, and the secretory component - in epithelial cells. To enter the secretions, IgA must overcome the dense epithelial layer lining the mucous membranes. Experiments with luminescent antiglobulin sera made it possible to follow the process of immunoglobulin secretion. It turned out that the IgA molecule can pass this way both through the intercellular spaces and through the cytoplasm of epithelial cells. Secretory IgA has a pronounced bactericidal, antiviral and antitoxic properties, activates complement, stimulates phagocytosis, plays a decisive role in the implementation of resistance to infection.
One of the important mechanisms of antibacterial protection of the oral cavity is the prevention of bacteria adherence to the surface of the cells of the mucous membranes and tooth enamel with the help of IgA. The justification for this assumption is that the addition of antiserum to S. mutans in a medium with sucrose prevented their fixation on a smooth surface in the experiment. IgA was detected on the surface of bacteria by immunofluorescence. It follows that the 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 protect the internal environment of the body from various agents that enter the mucous membranes.
Another way for the appearance of immunoglobulins in secrets is their entry from the blood serum: IgA enters the saliva from the serum as a result of extravasation through an inflamed or damaged mucous membrane. The squamous epithelium lining the oral mucosa acts as a passive molecular sieve, especially favoring IgG penetration. Normally, this route of entry is limited. It has been established that serum IgM is the least able to penetrate into saliva.
Factors that increase the flow of serum immunoglobulins into secretions are inflammation 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 expedient mechanism for enhancing local immunity.

MECHANISMS OF ORAL IMMUNITY

1. The oral cavity is the "entrance gate" for pathogens.

Together with food, breathing, when talking, a rich microflora enters the oral cavity, which may contain microorganisms of various pathogenicity. Thus, the oral cavity is an “entrance gate”, and its mucosa is one of the external barriers through which pathogenic agents can enter the body. As a gateway for many antigens and allergens, it is the scene of humoral and cellular immune responses. 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 one would expect. This is due, on the one hand, to the peculiarities of the structure 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. In the oral cavity are constantly substances of animal, vegetable 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, tooth tissues, dental plaques, epithelium of the tongue and cheeks; ABO blood group antigens - in the epithelium of the cheeks, tongue, esophagus. The antigenic spectrum of the normal oral mucosa is complex. It includes a set of species and organ-specific antigens. Significant differences were revealed in the antigenic structure of different sections of the oral mucosa: antigens present in the soft palate, absent in the mucosa of the hard palate, cheeks, tongue, and gums. The antigenic spectrum of the normal oral mucosa is complex. It includes a set of species and organ-specific antigens. Significant differences were revealed in the antigenic structure of different parts of the oral mucosa: antigens present in the soft palate, absent in the mucosa 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 nature, formed in the process of evolutionary development and providing protection to the mucous membranes of those organs that directly communicate with the external environment. Its main function is to preserve the homeostasis of the internal environment of the macroorganism, i.e. it is the first barrier on the way of a microorganism and any antigen. The local defense system of the oral mucosa is composed of factors non-specific protection and specific mechanisms of immunity; antibodies and T-lymphocytes directed against a specific antigen.

3. Secret functions oral cavity and its composition. The oral fluid (mixed saliva) consists of a secret secreted by the salivary glands and a crevicular (slit) gingival fluid, which is 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 in the course of active processes occurring 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 non-specific factors and some indicators of specific immunity.

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

Complement is a complex multicomponent system of proteins, including 9 fractions. Only a fraction of the C3 complement system is found in saliva in small quantities. The rest are absent or found in trace amounts. 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 numbers from the gum crevices and tonsils; moreover, 80% of their composition is represented by polymorphonuclear neutrophils and monocytes. Some of them, getting into the oral cavity, die, releasing lysosomal enzymes (lysozyme, peroxidase, etc.), which contribute to the neutralization of pathogenic and opportunistic flora. The remaining leukocytes in the mucosa, having phagocytic activity, create a powerful protective barrier to the development of the infectious process. A slight phagocytic activity is necessary and sufficient to capture the food particles remaining in the oral cavity, the microorganisms that have fallen with them and thereby clean the oral cavity. At the same time, when foci of inflammation appear in the oral cavity, the local activity of salivary leukocytes can significantly increase, thus carrying out 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, 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, regenerative processes. With 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 in antibacterial and antiviral protection are antibodies - immunoglobulins. Of the five known classes of immunoglobulins (IgA, IgM, IgG, IgD, IgE), the most significant in the specific immunity of the oral cavity are class A antibodies, moreover, 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 provides 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 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. Factors capable of stimulating the synthesis of slgA include lysozyme, vitamin A, a complete balanced diet (vitamins, microelements, etc.).

IgG and IgA penetrating from the bloodstream into the oral secretion are quickly inactivated by salivary proteases and thus are unable to perform their protective function, and antibodies of classes M, E and D are detected in small quantities. The level of IgE reflects the allergic mood of the body, rising mainly in allergic diseases.

The vast majority of plasma cells of the mucous membranes and all glands of external secretion produce IgA, since T-helpers predominate in the cells of the mucous membranes, 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 secretion of the oral cavity can be in free form (binds the 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 cavity, which prevents the occurrence of an 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.

Due 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.

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

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

The mucous membrane of the oral cavity, populated by many 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, so it forms the 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 overexertion 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 redness, 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 often occurs in systemic diseases, diabetes and others 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. Late 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 reasons stomatitis - infection, trauma, irritating 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 bad smell from the mouth and saliva mixed with blood. The persistence and recurrent nature of such inflammatory lesions requires not only the usual hygienic measures for the care of the oral cavity and teeth, but also appropriate, reasonable therapy aimed at stimulating the protective forces of the oral mucosa. Therapy inflammatory diseases of the oral mucosa In the light of the pathophysiological data presented, the immunological way of solving the problem allows us to propose a treatment that has two main effects - the treatment of active inflammatory disease 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 an 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 with a mild course of the disease, 8-10 days - with moderate diseases, 15 days - in severe cases. 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). Thanks to the pleasant mint taste, the children took it with pleasure, complications and side effects drug was 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 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 with 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 in recommended doses, it is 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.

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Introduction

1. Non-specific factors of resistance (protection) of the oral cavity

2. Immune protective factors of the oral cavity

3. Immunoglobulins A

4. Clinical and laboratory manifestations of immunodeficiency states in the oral cavity

5. General principles correction of immunodeficiencies

References

Vconducting

oral mucosa immunodeficiency

The mucous membrane of the oral cavity is inhabited by a wide variety of microorganisms and is the place of balance between the protective forces and the bacterial flora. With a decrease in immunity, as a result of excessive bacterial activity, this balance is disturbed, which provokes the development of an infection in the mouth. The mucous membrane is an excellent target for pathogenic microorganisms that enter there in a variety of ways. Protection of the oral cavity occurs in non-specific and specific (immunological) ways.

Nonspecific protective factors are associated with the structural features of the oral mucosa, the protective properties of saliva (oral fluid), as well as with the normal microflora of the oral cavity. Specific factors are provided by the functioning of T-, B-lymphocytes and immunoglobulins (antibodies). Specific and non-specific factors protection are interconnected and are in dynamic equilibrium.

1 . Nonspecific factors of resistance (protection) of the oral cavity

Barrier function of the skin, mucous membranes, role normal microflora, the value of the oral fluid, its humoral and cellular factors.

Allocate mechanical, chemical (humoral) and cellular nonspecific defense mechanisms.

M mechanical protection carried out by the barrier function of the intact mucous membrane by washing off microorganisms with saliva.

Saliva, in addition to washing off microorganisms, also acts bactericidal, due to the presence of biologically active substances in it.

Chemical (humoral) ) factors.

The humoral protective factor is saliva enzymes:

Lysozyme- mucolytic enzyme. It is found in all secretory fluids, but in the greatest amount in lacrimal fluid, saliva, and sputum.

The protective role of lysozyme, as well as other salivary enzymes, can manifest itself in a violation of the ability of microorganisms to be fixed on the surface of the oral mucosa or tooth surface.

Beta lysines- bactericidal factors that are most active against anaerobic and spore-forming aerobic microorganisms.

Complement- whey protein system (about 20 proteins). Complement is a system of highly efficient proteases capable of lysing bacteria.

Interferons- antiviral cytokites synthesized by leukocytes. All types of interferon have antiviral, immunomodulatory and antiproliferative effects.

Cellular non-specific defense factors . They are represented by phagocytosis and the natural killer system:

Fagocytosis- this is phylogenetically the most ancient form of a non-specific protective reaction of the body. In the mixed saliva of a person, leukocytes and lymphocytes are always found that enter the oral cavity through the epithelium of the gingival pockets. Natural killer (NK-cell) system. They function primarily as effectors of antiviral and antitumor immunity.

2 . Specific (immune)protective factors in the oral cavity

There are cellular and humoral immune defense mechanisms.

Cellular mechanisms immune defenses are mediated mainly by T-lymphocytes and macrophages, which are located in the submucosal layer and are part of MALT (mucosal-associated lymphoid tissue). T-helpers of the first order (CD4, Th I) synthesize IFN-g, attract activated macrophages to the inflammation site and mediate the development of delayed-type hypersensitivity. An essential protective role is played by CD8 (cytotoxic) lymphocytes, which realize contact cytotoxicity (due to the production of perforins and granzymes). T-helpers of the second (Th II) order (CD4) ensure the activation of B-lymphocytes and the production of antibodies.

Humoral mechanisms The main factor of specific humoral antimicrobial protection are immune gamma globulins (immunoglobulins).

Immunoglobulins - protective proteins of blood serum or secretions that have the function of antibodies and are related to the globulin fraction of proteins. There are 5 classes of immunoglobulins: M, A, G, E, D. 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 in human blood serum IgG is mainly represented, IgA is 2-4 times less, and IgM is contained in a small amount, 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. The ratio of IgA, IgG, IgM in saliva is about 20:3:1.

3 . Immunoglobulin A

In the human body, IgA makes up about 10-15% of all serum Ig. IgA is present in the body in two varieties: serum and secretory.

Whey IgA in its structure is not much different from IgG and consists of two pairs of polypeptide chains connected by disulfide bonds.

Secretory immunoglobulin A is found predominantly in secretions of mucous membranes - in saliva, lacrimal fluid, nasal secretions, sweat, colostrum and secretions of the lungs, urogenital tract and gastrointestinal tract, where it provides protection for surfaces communicating with external environment, from microorganisms and the gastrointestinal tract and mucous membranes of the oral cavity. But the protection mechanism will be discussed later. For now, let's study the structure of immunoglobulin A. A distinctive feature is that it is resistant to the action of proteolytic enzymes (this is of great biological importance). The latter are contained in secrets (saliva, gastric juice, etc.) secreted by the oral mucosa. Microorganisms that make up the dental bacterial plaque enhance their synthesis

The structure of secretory immunoglobulin A

The general plan of the structure of IgA corresponds to other immunoglobulins. The dimeric form is formed through a covalent bond between the J chain (J) and amino acids. In the process of IgA transport through epithelial cells, a secretory component (SC) is attached to the molecule. (fig. on slide 8)

J-chain (English joining - accession) is a polypeptide of 137 amino acid residues. The J-chain serves to polymerize the molecule, i.e. to connect two protein subunits of immunoglobulins (approximately 200 uA) via disulfide bonds

The secretory component consists of several antigenic related polypeptides. It is he, together with the J-chain, that contributes to the protection of IgA from proteolysis. The secretory component of IgA is produced by the cells of the serous epithelium of the salivary glands. 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 secrets. In addition, isolated cases are described when, in case of impaired production of serum IgA (for example, a sharp increase in its level in A-myeloma, disseminated lupus erythematosus), the level of IgA in secrets remained normal.

Transport of immunoglobulin A into the secretory fluid.

In clarifying the question of the mechanism of secretory IgA synthesis, research using luminescent antisera is of great importance. It has been established that IgA and the secretory component are synthesized in different cells: IgA - in plasma cells of the lamina propria of the oral mucosa and other body cavities, and the secretory component - in epithelial cells. To enter the secretions, IgA must overcome the dense epithelial layer lining the mucous membranes. Experiments with luminescent antiglobulin sera made it possible to follow the process of immunoglobulin secretion. It turned out that the IgA molecule can pass this way both through the intercellular spaces and through the cytoplasm of epithelial cells. Consider this mechanism: (Fig. 9 slide)

From the main circulation, IgA penetrates into epithelial cells, interacting with the secretory component, which at this stage of transport acts as a receptor. In the epithelial cell itself, the secretory component protects IgA from the action of proteolytic enzymes. Having reached the apical surface of the cell, the IgA:secretory component complex is released into the secretion of the subepithelial space.

Of other immunoglobulins synthesized locally, IgM predominates over IgG (inverse ratio in blood serum). There is a mechanism of selective transport of IgM through 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 deficiency of IgA or IgM. Individuals resistant to caries have high levels of IgA and IgM.

Another way for the appearance of immunoglobulins in secrets is their entry from the blood serum: IgA and IgG enter the saliva from the serum as a result of extravasation through an inflamed or damaged mucous membrane. The squamous epithelium lining the oral mucosa acts as a passive molecular sieve that favors IgG penetration. Normally, this route of entry is limited. It has been established that serum IgM is the least able to penetrate into saliva.

Factors that enhance the flow of serum immunoglobulins into secrets are inflammatory processes of the oral mucosa, its trauma. In such situations, the supply of a large amount of serum antibodies to the site of action of the antigen is a biologically expedient mechanism for enhancing local immunity.

Immunological role of IgA

Secretory IgA has a pronounced bactericidal, antiviral and antitoxic properties, activates complement, stimulates phagocytosis, plays a decisive role in the implementation of resistance to infection.

One of the important mechanisms of antibacterial protection of the oral cavity is the prevention of bacteria adherence to the surface of the cells of the mucous membranes and tooth enamel with the help of IgA. The justification for this assumption is that in the experiment, the addition of antiserum to Str. mutans in a medium with sucrose prevented their fixation on a smooth surface. IgA was detected on the surface of bacteria by immunofluorescence. It follows from this that inhibition of bacterial fixation on the smooth surface of the tooth and oral mucosa may be an important function of secretory IgA antibodies that prevent the occurrence of a pathological process (dental caries). IgA inactivates the enzymatic activity of cariogenic streptococci. Thus, secretory IgA protect the internal environment of the body from various agents that enter the mucous membranes, which prevents the development of inflammatory diseases of the oral mucosa.

Also, in mammals, including humans, secretory IgA is well represented in colostrum and thus provides specific neonatal immunity.

Studying the formation of S IgA antibodies A lot of work has been devoted to the specific response to the oral microflora in humans. Thus, Smith and colleagues emphasize that the appearance of IgA antibodies to streptococci (S.salivaris and S.mitis) in newborns and older children directly correlates with the colonization of oral cavity by these bacteria in children. It was shown that secretory antibodies produced by the immune system of the oral mucosa against streptococci during colonization of the oral mucosa can affect the degree and duration of colonization, while contributing to the specific elimination of these microorganisms.

It can be hypothesized that these naturally found SIgA antibodies may play an important role in the homeostasis of the resident microflora of the oral cavity, as well as in the prevention of caries and periodontal, as well as maxillofacial diseases(actinomycosis, phlegmon, abscesses, etc.).

Due to the close interaction of specific (immunity) and non-specific (natural) resistance factors, the body, including the oral cavity, is reliably protected from infectious and non-infectious pathogenic factors of the external and internal environment.

4 . Clinical and laboratory manifestations of immunodeficiency states in the oral cavity

One of the manifestations of an immunodeficiency state in the oral cavity is dental caries. This is the most common human disease. Dental caries affects almost all adults and child population. About 90% of the population needs treatment for this pathology of the teeth. Numerous clinical and experimental studies have established that the impact of a complex of unfavorable exogenous and endogenous factors (past diseases, especially those of an infectious nature, malnutrition, prolonged stress, industrial intoxication, adverse climatic and geographic and geochemical conditions) causes inhibition of the body's immunoreactivity, which leads to the development of an immunodeficiency state. in the oral cavity and contributes to the development of caries. It is characteristic that the incidence of dental caries depends not so much on the nature of the disease, but on its severity, which determines the severity of the immunodeficiency state in general and in the oral cavity in particular.

A direct relationship between immunoreactivity, nonspecific resistance of the organism and the intensity of the carious process was revealed. This is confirmed by both experimental studies and clinical observations.

Immunodeficiency in the oral cavity enhances the formation plaque- white soft substance, localized in the neck of the tooth or on its entire surface, easily removed with a toothbrush.

Methods for assessing the immune status

Laboratory tests I level:

1. Determination of the specific gravity (%) and the absolute number of T-lymphocytes (CD3);

2. Determination of the number of B-lymphocytes (CD20, 22);

3. Determination of indicators of phagocytosis

Phagocytic activity or percentage of phagocytic neutrophils

Phagocytic number - the average number of microbes (or test particles) in 1 phagocyte;

4. Determination of the content of immunoglobulins of the main classes (IgM, IgG, IgA).

Laboratory tests II level:

1. Determination of subpopulations of T-lymphocytes: T-helpers (CD4), T-cytotoxic (CD8);

2. Determination of the functional activity of lymphocytes - in the reaction of blast transformation to PHA, ConA;

3. Determination of cytokines: pro-inflammatory (IL-1, TNF-b, IL-5, IL-6, IL-12, IFN), anti-inflammatory (IL-4, IL-10, IL-13, TGF-c), Th1 (T-helper type I) - IL-2, IFN-g, Th2 (T-helper type II) - IL-4, IL-10;

4. Determination of the components of the complement system;

5. Determination of oxygen-dependent and oxygen-independent mechanisms of bactericidal activity of neutrophils and macrophages;

6. Research secretory function macrophages;

7. Intradermal test with tuberculin to assess the state of T-cell immunity;

8. Determination of specific antibodies, circulating immune complexes.

9. Determination of markers of activation of immunocompetent cells.

The normogram of the main indicators of the immune status is presented in Table. one.

Table 1. Immune status

Indicators	Survey data	Indicators		Survey data
Leukocytes		abs. number
Lymphocytes		abs. number
Phagocytic index		abs. number
phagocytic number		Serum IgA
abs. number
abs. number
abs. number			30-50 units
abs. number
abs. number

Designations: Phagocytic index: % of leukocytes that absorbed the test particles; Phagocytic number: average number of absorbed particles; CD3 lymphocytes - T-lymphocytes; CD22 - B-lymphocytes; CD16 - natural killers; CD4 - T-helpers; CD8 - T-lymphocytes with cytotoxic and suppressor function; CD25 - activated T-lymphocytes with IL-2 receptor; CD54 - cells with ICAM-I molecules; CD95 - cells expressing the FAS receptor (apoptosis receptor); CEC - circulating immune complexes.

5. General principles for the correction of immunodeficiencies

1. Chemotherapy and prevention. Chemoprophylaxis can significantly improve the prognosis of hypogammaglobulinemia. Prophylactic administration of antibiotics is used only for combined immunodeficiencies to prevent the threat of infectious complications, fungal infections. High doses of narrow-spectrum antibiotics are usually recommended. The issue of immunization remains open. In addition, it should be remembered that in case of violations of cellular immunity, the use of live vaccines is absolutely excluded, since this can lead to generalized processes.

2. Replacement therapy . Blood transfusion in T-cell and combined immunodeficiency is associated with the threat of graft-versus-host disease. The safest transfusion is fresh blood, which is previously irradiated to suppress the antigenic properties of lymphocytes. Replacement therapy is a way to treat hypo- and dysgammaglobulinemia. Official preparations of immunoglobulins are used - pentoglobin, octagam, human immunoglobulin, cytotec and others. At the same time, it should be borne in mind that unwanted reactions in the form of fever, tachycardia, collapse, suffocation, and even anaphylactic shock due to the presence of aggregated forms of immunoglobulins or the production of antibodies to IgA may occur on the administered gamma globulin.

3. Thymus transplant and the use of drugs derived from it (thymalin, thymogen). It is also believed that it is possible to restore the immunological competence of the body with the help of transplantation of lymphoid organs and tissues, especially since immunodeficiencies are accompanied by a weakening of the reactions of transplantation immunity. It is recommended to use the thymus of an embryo that has not reached 14 weeks, i.e. until they acquire immunological tolerance. Bone marrow transplantation is effective. The question of the use of stem cells is being discussed.

4. Administration of drugs derived from lymphoid tissue. A transfer factor (transfer factor) is used - an extract from donor's peripheral blood lymphocytes. With the help of it, it is possible to stimulate T-cell immunity, enhancing the synthesis of interleukin-2, the production of gamma-interferon, and increasing the activity of killers. With B-cell immunodeficiencies, myelopid is used (a drug of bone marrow origin). In severe combined immunodeficiency, transfer factor administration is usually combined with thymus transplantation.

5. With immunodeficiency, due to the reduced activity of adenosine deaminase, it is recommended to administer frozen erythrocytes (success in 25-30%). With a deficiency of purine nucleoside phosphorylase, the effect is achieved by bone marrow transplantation.

6. The use of immunomodulating drugs of different groups, depending on the identified defect (T-, B-lymphocytes, NK-cells, macrophage deficiency, antibody deficiency, etc.). For example, in case of insufficiency of the T-link of immunity and a violation of the activation process of the Th1 type, it is rational to use recombinant IL-2 (roncoleukin), which binds to the Th receptor (CD25) and stimulates their functional activity.

Bibliography

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2. Benevolenskaya L.M. The problem of osteoporosis modern medicine// Bulletin of the Russian Academy of Medical Sciences. - 2003. - No. 7. With. 15-18.

3. Gostishchev V.K. General surgery. Proc. - M.: GEOTAR - MED, 2001. - 608 p.: ill. - (Series "XXI century")

4. Zaichik A.Sh., Churilov L.P. Fundamentals of general pathology. Part 2, Fundamentals of pathochemistry. - St. Petersburg, ELBI, 2000. - p. 616-641.

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Nonspecific oral defense factors. The immune system of the oral mucosa

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