The relationship between the function of local immunity and intestinal microbiocenosis, the possibility of immunocorrection of dysbiosis. The immune system is hidden in the intestines; Microflora and health Immune cells are found in the intestines

Immunity is the body’s ability to recognize and neutralize a foreign object. The task of immunity is to ensure the constancy of the body at the cellular level and at the general level. It is carried out with the help of the immune system.

The immune system consists of:

• central authorities;
• thymus;
• red bone marrow;
• peripheral organs;
• lymph nodes;
• spleen;
• locally associated bronchopulmonary lymphoid tissues;
• locally associated intestinal lymphoid tissues;
• locally associated skin lymphoid tissues.

Immunity functions:

Alimentary (through the digestive system, “dirty hands” disease) route of infection is the leading mechanism for infection to enter the body. In addition to infection, helminths, protozoa, poisonous substances of inanimate nature can enter our body through the gastrointestinal tract. The intestines help our body cope with all these threats.

The intestine is the most important organ of the immune system, because it contains the largest number of immune cells.

The main nodes in the intestinal immune system:

• Peyer's patches;
• appendix;
• lymph nodes.

Mechanism of immunity implementation

Intestinal immunity is carried out by special cells - lymphocytes, which produce specific substances - immunoglobulins, which, in turn, recognize infections, determine the degree of threat, and fight it. Immunoglobulins come in different types.

Secretory immunoglobulin A prevents foreign bacteria from attaching to the intestinal walls - the main "orderly". Immunoglobulin M - first enters our body with mother's breast milk, helps to recognize where there is danger and where it is a completely harmless bacterium - this is memory immunoglobulin. The successful cooperation of these two immunoglobulins allows us not only to protect ourselves from foreign pathogenic bacteria, but also to help beneficial bacteria attach to the intestinal wall and guard our health.

Not the least important place in intestinal immunity is occupied by biofilm, lining the entire surface of the organ; it protects our body not only from bad bacteria, but also from chemical and physical irritants.

The activity and consistency of the immune response to the infectious agent depends on a number of factors:

• absence or presence of damage to the organ biofilm;
• maturity of the immune system;
• acute and chronic intestinal infections;
• nutrition;
• the overall potential of the human immune system.

In order for the intestine to be able to fully protect the body from a foreign aggressor, there are a number of mechanisms. Throughout the intestine, it is covered with a dense film of glycocalyx, which protects it from mechanical damage. There are lymphocytes in the mucous membrane, which, if necessary, will not only fight the enemy, but also “call” cells from other immune organs, increasing blood supply. The alternation of sections of the intestine with an acidic environment with sections of an alkaline nature help not to miss any type of bacteria. And most importantly, the entire surface of the mucous membrane is densely populated with beneficial microflora, which simply does not allow pathogenic bacteria to settle.

Intestinal microflora and its role in immunity

The entire surface of the intestine is inhabited by microorganisms, with the exception of only the initial section of the small intestine due to the highly acidic environment of the microflora unsuitable for life.

The main share of microorganisms in the digestive system are lactobacilli and bifidobacteria. These intestinal bacteria are an integral part of the biofilm. Normal flora not only prevents foreign pathogenic bacteria from attaching to the wall of the organ, but also suppresses the reproduction of already attached microorganisms by competing for the necessary nutrients.

In addition, normal intestinal flora helps the body digest food; they are able to break down plant fibers. With a decrease in the number of beneficial bacteria, the permeability of the mucous membrane to food macromolecules increases. The ability of the intestines to produce immunoglobulin A is also reduced.

The importance of a normal balance of microflora in the intestines can be confirmed by the fact that newborns adapt to independent digestion of food over a period of time. While the immune system has not yet matured, the newborn receives the necessary immunoglobulins, in particular A, with mother’s milk, which helps the normal microflora take its place in the biofilm. But in the absence of breastfeeding, this process is disrupted, as a result, the baby’s body is populated by conditionally pathogenic microflora, which leads to immunity disorders and the frequent occurrence of allergies.

Causes of microflora disturbances

The balance in the intestinal microflora system is very easy to disturb; beneficial bacteria can be knocked out of action by various factors:

• Antibiotics. Patients are often prescribed antibiotics to fight infections. These are very effective medicinal substances, but their disadvantage is poor selectivity; in other words, they don’t care who they kill - evil microbes or beneficial microflora.
• Treatment with chemotherapy or radiation therapy.
• Diseases with enzymatic disorders.
• Systemic diseases - cancer, AIDS.
• Tap water. To disinfect and purify drinking water, chemical substances fluorine and chlorine are introduced into its composition. These substances kill the body's microflora.
• Bad ecology.
• Malnutrition, etc.

The composition of the intestinal microflora is greatly influenced by the nature of the food we eat. Thus, an excess amount of sugar in food can lead to increased proliferation of fungi of the genus Candida and, as a result, candidiasis. Sugar is a favorite treat for candida.

Overeating is also unacceptable. If the digestive system does not have time to cope with the entire volume of food received, then the processes of decomposition and rotting begin in the intestines, which also lead to the death of healthy microflora, and therefore to the growth of conditionally pathogenic ones.

The presence of helminthic infestation has a very adverse effect on the microflora and immunity of the whole organism. The presence of diseases that change the intestinal environment (hepatitis, gastritis, peptic ulcer, cholecystitis) will also not have the best effect on the number of beneficial bacteria.

A low amount of enzymes as a result of dysfunction of the pancreas, stomach, and liver will also disrupt the composition of the microflora.

Symptoms of dysbiosis

The diagnosis of dysbacteriosis can only be made by your attending physician based on the results of stool culture for microflora. But the main symptoms of dysbiosis can be considered:

• vomit;
• diarrhea;
• nausea;
• belching;
• bad breath;
• bloating;
• abdominal pain, etc.

Treatment for dysbacteriosis

Typically, treatment of dysbiosis is carried out in several stages.

First of all, it is necessary to normalize the conditions in the intestines for normal microflora. Therefore, stress and excessive physical activity should be avoided, sleep and wakefulness should be observed, and diet should be adjusted.

You should not eat fatty, sour, or any spicy irritating foods. Food should be rich in vitamins, with the right balance of proteins, fats and carbohydrates. There should not be long gaps between meals. The last meal should be taken no later than 3 hours before bedtime. It is also important to eat slowly, chewing your food thoroughly.

The second stage should be to reduce the number of pathogenic microbes. This is achieved through the use of medications - nitroxoline, furazolidone and the like. Typically, antiseptics are prescribed for 10-14 days.

Next, you need to populate the intestinal walls with beneficial microflora. To do this, it is necessary to combine the use of probiotics and prebiotics. Probiotics are preparations consisting of beneficial intestinal bacteria. The most suitable bacteria are bifidobacteria and lactobacilli, which means the drugs Enterol, Bifiform, Linex, Bifidumbacterin and others are suitable. Prebiotics are drugs that maintain a favorable microclimate in the intestines for normal microflora. Of the prebiotics, the most popular is Hilak Forte.

It is also necessary to increase general immunity, drink vitamins and sorbents.

Folk methods to strengthen intestinal immunity

If you do not want to use medications, then regular serum can help you in the fight against dysbiosis. It’s not difficult to prepare; just heat the kefir, which will curdle and separate into cottage cheese and whey.

You can also use garlic buttermilk. To do this, boil the milk, wait until it cools completely. Then fermented with black bread croutons for 24 hours. After that, add more croutons rubbed with garlic to it. Can be stored in the refrigerator and eaten as desired.

To increase intestinal immunity, it is also considered very useful to eat strawberries on an empty stomach in the morning, preferably 1 glass for 10 days.

Conclusion

Intestinal immunity is an important link in the entire immune system of the body, and therefore our safety. Follow all the principles of a healthy lifestyle: eat well, have a good rest, avoid stress, monitor the general condition of the body! And then nothing threatens your intestinal immunity! Be healthy!

The gastrointestinal tract represents the most extensive habitat of microflora in the body, since its surface area is more than 300 m 2 . The intestinal biocenosis is open, that is, microbes from the outside can easily get there with food and water. To maintain the relative constancy of the internal environment, the digestive tract has powerful antimicrobial defense mechanisms, the main of which are the gastric acid barrier, active motility and immunity.

Cellular elements:

The structural elements of the GALT system carry out an adaptive immune response, the essence of which is the interaction between antigen-presenting cells (APCs) and T-lymphocytes, which is controlled by immunological memory cells.

Protective mucus barrier includes not only immune, but also non-immune factors: a continuous layer of columnar epithelium with close contact of cells with each other, a glycocalyx covering the epithelium, membrane digestion enzymes, as well as membrane flora associated with the surface of the epithelium (M-flora). The latter, through glycoconjugated receptors, connects to the surface structures of the epithelium, enhancing mucus production and thickening the cytoskeleton of epithelial cells.

Toll-like receptors (Toll-like-receptors - TLR) belong to the elements of the innate immune defense of the intestinal epithelium, recognizing “friends” from “strangers”. They are transmembrane molecules that connect extra- and intracellular structures. 11 types of TLRs have been identified. They are able to recognize specific patterns of intestinal bacterial antigen molecules and bind them. Thus, TLR-4 is the main signaling receptor for lipopolysaccharides (LPS) of Gram(-) bacteria, thermal shock proteins and fibronectin, TLR-1,2,6 - lipoproteins and LPS of Gram(+) bacteria, lipoteichoic acids and peptidoglycans, TLR- 3 - viral RNA. These TLRs are located on the apical membrane of the intestinal epithelium and bind antigens on the surface of the epithelium. In this case, the internal part of the TLR can serve as a receptor for cytokines, for example, IL-1, IL-14. TLR-5 is located on the basolateral membrane of the epithelial cell and recognizes the flagellins of enteroinvasive bacteria that have already penetrated the epithelium.

TLR receptors in the gastrointestinal tract provide:

• Tolerance to indigenous flora
• Reducing the likelihood of allergic reactions
• Antigen delivery to antigen presenting cells (APCs)
• Increasing the density of intercellular connections
• Induction of antimicrobial peptides

Antimicrobial peptides secreted by both circulating cells and epithelial cells of the gastrointestinal tract and are nonspecific factors of humoral immune defense. They may vary in structure and function. Large proteins perform the function of proteolytic enzymes, lysing cells, and small proteins disrupt the structure of membranes, forming gaps with subsequent loss of energy and ions from the affected cell and subsequent lysis. In humans, the main classes of antimicrobial peptides are cathelicidins and defensins; among the latter, alpha- and beta-defensins are distinguished.

Defensins are small cationic peptides; in neutrophils they participate in the oxygen-independent destruction of phagocytosed microbes. In the intestines, they control the processes of attachment and penetration of microbes. Beta-defensins are characterized by individual variability and are present in almost all parts of the gastrointestinal tract, pancreas and salivary glands. They bind to dendritic cells, which express the chemokine receptor and regulate the chemotaxis of dendritic cells and T cells. As a result, defensins take part in the adaptive phase of the immune response. Defensins can stimulate the production of IL-8 and neutrophil chemotaxis, causing degranulation of mast cells. They also inhibit fibrinolysis, which contributes to the spread of infection, alpha-defensins HD-5 and HD-6 are found in Paneth cells deep in the crypts of the small intestine. The expression of HD-5 is increased in any inflammation of the intestine, and HD-6 - only in inflammatory bowel diseases, hBD-1 alpha-defensin is the main defense of the intestinal epithelium, preventing the attachment of microorganisms in the absence of inflammation. Expression of hBD-2 is a response to inflammatory and infectious stimuli.

In humans, only one cathelicidin, LL-37/hCAP-18, has been isolated; it is found in the upper part of the crypts of the large intestine. Increased expression of it is observed in some intestinal infections, it has a bactericidal effect.

intestinal epithelium performs not only a barrier function, but also ensures that the body receives nutrients, vitamins, microelements, salts and water, as well as antigens. The mucous barrier does not represent an absolutely insurmountable obstacle; it is a highly selective filter that provides controlled physiological transport of particles through the “epithelial openings”, thereby allowing the persorption of particles up to 150 mm in size. The second mechanism for the entry of antigens from the intestinal lumen is their transport through M-cells, which are located above Peyer's patches and do not have microvilli, but have microfolds (M-microfolds). By endocytosis, they transport macromolecules through the cell, during the transport process the antigenic structures of the substance are exposed, dendritic cells are stimulated on the basolateral membrane, and in the upper part of the Peyer's patch the antigen is presented to T lymphocytes. Antigens presented to T helper cells and macrophages are recognized and, if there are receptors corresponding to the antigen on the cell surface, Th0 cells are transformed into Th1 or Th2. Transformation to Th1 is accompanied by the production of so-called pro-inflammatory cytokines: IL-1, TNF-α, IFN-γ, activation of phagocytosis, migration of neutrophils, increased oxidative reactions, synthesis of IgA, all these reactions are aimed at eliminating the antigen. Differentiation into Th2 promotes the production of anti-inflammatory cytokines: IL-4, IL-5, IL-10, usually accompanies the chronic phase of inflammation with the production of IgG, and also promotes the formation of IgE with the development of atopy.

B lymphocytes During the response, the GALT systems are transformed into plasma cells and leave the intestine into the mesenteric lymph nodes, and from there through the thoracic lymphatic duct into the blood. With the blood they are carried to the mucous membranes of various organs: the oral cavity, bronchi, genitourinary tract, and also to the mammary glands. 80% of lymphocytes return back to the intestines, this process is called homing.

In adults, immunoglobulins of all classes are found in the gastrointestinal tract. In the jejunum, per 1 mm 3 of tissue there are 350,000 cells secreting IgA, 50,000 secreting IgM, 15,000 IgG, 3000 IgD, the ratio of cells producing Ig A, M and G is 20:3:1. The intestinal wall is capable of synthesizing up to 3 g of immunoglobulins per day, and there is no correlation between their content in plasma and intestinal juice. Normally, the predominant class of immunoglobulins in the intestine is secretory IgA (SIgA). It plays a major role in the specific humoral protection of the mucous membrane, covering it like a carpet and preventing the attachment of microbes to the epithelium, neutralizing viruses, and delaying the penetration of soluble antigens into the blood. Interestingly, M cells predominantly capture antigens in complex with IgA, followed by stimulation of IgA production. SIgA, which is synthesized in the form of a dimer, is well adapted to function in the intestine - it is resistant to the effects of proteolytic enzymes. Unlike IgG, the main systemic immunoglobulin, SIgA is not a companion to inflammation. It binds antigens on the surface of the mucous membrane, preventing their penetration into the body and thereby preventing the development of inflammation.

The main function of the GALT system is the recognition and elimination of antigens or the formation of immunological tolerance to them. The formation of immunological tolerance is the most important condition for the existence of the gastrointestinal tract as a barrier on the border of the external and internal environment. Since both food and normal intestinal microflora are antigens, they should not be perceived by the body as something hostile and rejected by it, they should not cause the development of an inflammatory response. Immunological tolerance to food and obligate intestinal microflora is provided through the suppression of Th1 by interleukins IL-4, IL-10 and stimulation of Th3 with the production of TGF-β, provided that low concentrations of the antigen are received. High doses of antigen cause clonal anergy, with T-lymphocytes becoming unable to respond to stimulation and secrete IL-2 or proliferate. TGF-β is a nonspecific, potent suppressor factor. Perhaps, the formation of oral tolerance to one antigen contributes to the suppression of the immune response to others. TGF-β promotes the switching of immunoglobulin synthesis from IgM to IgA. Immunological tolerance is also provided by the synthesis of the Toll-inhibiting protein (Tollip) and the associated decrease in TLR-2 expression.

The effectiveness of the GALT system depends on the colonization of the intestine with indigenous microflora. To carry out the interaction between them, M-cells of the intestinal mucosa permanently transport microbial antigens and present them to lymphocytes, inducing their transformation into plasmacytes and homing. With the help of this mechanism, controlled opposition to antigenic material foreign to the body and its own microflora and coexistence with it is carried out. A clear example of the enormous importance that physiological microflora has are the results of studies on animals raised in sterile conditions - gnotobionts. In the absence of microbes, mammals have a low number of Peyer's patches and a more than 10-fold decrease in IgA-producing B lymphocytes. The number of granulocytes in such animals was reduced, and the existing granulocytes were not capable of phagocytosis; the lymphoid structures of the body remained rudimentary. After implantation of representatives of normal intestinal flora (lactobacillus, bifidobacteria, enterococci) into sterile animals, they developed immune structures of GALT. That is, the intestinal immune system matures as a result of interaction with intestinal microflora. This experimental model reflects the normal ontogenetic processes of parallel formation of biocenosis and the intestinal immune system in newborns.

Over the past decades, industrialized countries have seen a significant increase in allergic diseases. There is a hypothesis that it is associated with a decrease in exposure to microbial antigens as a result of increased hygiene and active vaccination. Probably, a decrease in the stimulatory effect of bacterial antigens switches the differentiation of Th-lymphocytes from Th1 (with the production of IL-6, IL-12, IL-18, IFN-γ and IgA) predominantly to Th2 (with the production of IL-4, IL-10 and IgG and IgE). This can contribute to the formation of food allergies.

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A person's immunity depends on the condition of his intestines. A healthy body maintains a balance of microflora, which serves as protection against the invasion of viruses and pathogenic bacteria.

Literally, “immunity” is translated from Latin as immunity to disease. But this is not only protection from infectious diseases, but also from the body’s own damaged cells.

Man and the environment are a single ecological system in a state of biological equilibrium. The balance of microorganisms in the human intestine, on his skin and mucous membranes, is maintained constant and performs many functions.

From the standpoint of modern science, normal intestinal microflora can be considered as a set of microorganisms that constantly populate the digestive tract and protect it from pathogenic bacteria. They have a bactericidal and bacteriostatic effect, provide anti-infective protection and the functioning of the immune system.

Under normal physiological conditions, microorganisms inhabiting the human gastrointestinal tract perform various vital functions, including ensuring the processes of digestion and absorption of food, intestinal motor function, and the synthesis of vitamins, enzymes, and amino acids.

The human microflora includes more than 500 species of microorganisms. This entire system is in relative balance. Microorganisms are in constant interaction with each other. Populations of microbes cover the mucous membranes of the intestines, they reject strangers who do not belong to their community. They consume nutrients that could be used by harmful bacteria that enter the body. Under the influence of normal intestinal flora, the activity of macrophages, monocytes and granulocytes that protect the body increases.

Human microorganisms produce enzymes, vitamins, hormones, antibiotic natural substances, and participate in the processing of carbohydrates, fats and proteins, providing the human body with energy. Therefore, it is very important to keep the microflora in order: do not poison with antibiotics, alcohol and poor-quality food.

Today, a huge number of “miracle products” containing very “beneficial” bacteria are advertised. Manufacturers claim that these “superfoods” will help restore the natural intestinal microflora, without telling them that the body’s own flora will fight them as if they were enemies.

It is impossible to regulate all the relationships of hundreds of species of organisms with the help of a “pill”. The maximum that we can do is to try to create “comfortable conditions” for our own intestinal bacteria so that they themselves maintain their numbers and work actively.

It is very important to eat regularly and variedly, avoid constipation, move and drink plenty of fluids. Then the intestines will cope with their functions fully and the health of the body will be ensured.

Everyone knows the terrible word “dysbacteriosis”. We know that we need to fight it, monitor the nutrition and health of the microflora. But what is dangerous about dysbiosis besides indigestion? What is the main problem? There is a direct relationship between immunity and gut health. Let's figure out what it consists of.

Immunity is the ability of our body to find and neutralize foreign elements. The task of immunity is the constancy of the body, protection from external aggressive influences.

The main organs of the immune system are: the spleen, thymus (thymus gland), lymph nodes, partly the liver and red bone marrow, as well as all lymphoid tissue, tonsils, adenoids, appendix and intestines.

The alimentary (through the digestive system) route of infection is the main mechanism for infection to enter the body. In addition to infection, helminths, protozoa, and toxic substances can enter our body through the gastrointestinal tract. The intestines help our body cope with all these threats.

The intestine is the most important organ of the immune system, because it contains the largest number of immune cells.

The main components of the intestinal immune system:
Peyer's patches;
Appendix;
Lymph nodes.

Two-thirds of all immune cells in the body function in the intestines. Intestinal immunity is carried out by special cells - lymphocytes, which produce specific substances - immunoglobulins. Immunoglobulins are protein molecules that recognize the pathogen and block it.
Intestinal biofilm (a layer of “our” beneficial bacteria) lines the entire surface of the intestine and protects against pathogenic bacteria, chemicals, and other harmful influences.

The activity and consistency of the intestinal immune response in response to the infectious agent depends on a number of factors:
Conditions of the intestinal mucosa;
Absence or presence of damage to the intestinal biofilm;
Acute and chronic intestinal infections;
Food.

The entire surface of the intestine is populated by beneficial bacteria of the human microflora (except for the initial section of the small intestine, where the environment is too acidic for bacteria to live). The bulk of human microflora are bifidobacteria and lactobacilli. These bacteria make up the intestinal biofilm, which protects the intestines from colonization by pathogenic bacteria.

The balance in the intestinal microflora system is quite easy to upset. The violation may be caused by:
Antibiotics. These effective drugs have low selectivity. Together with the infection bacteria, they also destroy the beneficial bacteria of the intestinal microflora;
Treatment with chemotherapy or radiation therapy;
Chronic and severe diseases;
Drinking water treated with chlorine and fluoride;
Bad ecology;
Poor nutrition;
Stress.

Intestinal immunity is an important link in the entire human immune system. This is a guarantee of health safety. It is necessary to follow the correct principle and diet, avoid stress and monitor the overall health of the body.

A German drug will help preserve and restore intestinal immunity.
contains everything necessary for the health of the intestinal microflora: vitamins and microelements, prebiotics (nutrients for beneficial bacteria), probiotics (beneficial microorganisms of the human microflora).

The gastrointestinal tract (GIT) performs not only a digestive, but also an immune function, in particular, it participates in the implementation of the body’s defense reactions against pathogenic, conditionally pathogenic microorganisms and many inorganic substances.

Local intestinal immunity

About 80% of all immunocompetent cells of the body are localized in the intestinal mucosa; about 25% of the intestinal mucosa consists of immunologically active tissue and cells; Each meter of intestine contains about 1010 lymphocytes.

The immunocompetent (lymphoid) tissue of the gastrointestinal tract is represented by organized structures (Peyer's patches, appendix, tonsils, lymph nodes) and individual cellular elements (intraepithelial lymphocytes, plasma cells, macrophages, mast cells, granulocytes). The population of lymphoid tissue cells is heterogeneous and consists of many groups, subgroups and clones of cells with different functional properties and antigen receptor specificity.

The epithelium of the gastrointestinal tract delimits the tissues of the macroorganism from a huge number of living and non-living antigens - substances that carry signs of foreign genetic information. Oral exposure to an antigen (including microbes and their toxins) usually creates, on the one hand, local “mucosal” IgA protection (secretory immunity) and a cell-mediated reaction, but, on the other hand, systemic tolerance or hyporeactivity - suppression of subsequent the production of antigen-specific antibodies of classes G and M and the development of cell-mediated immunity. In relation to pathogenic and opportunistic microorganisms, the local intestinal immune system must show adequate protective properties, and in relation to normal flora - at least tolerance, and in the best case - actively participate in the processes of adhesion, survival and reproduction of representatives of normal flora.

Specific immune mechanisms are developed by the intestines to protect against potentially dangerous microorganisms throughout life. Undifferentiated lymphocytes, mostly producing secretory IgA or IgM antibodies, are present in the stratum propria or Peyer's patches. Stimulation of B and T lymphocytes in the presence of a foreign antigen occurs following their exit from the mesenteric nodes into the thoracic duct, the bloodstream and return to the intestine, where they also accumulate in the own layer of the mucous membrane. Activated cells produce specific antibodies of the IgA and IgM classes, which are secreted on the surface of the mucous membrane 4-8 days after stimulation. Immunoglobulins form complexes with antigens, neutralize toxins, prevent contact of microorganisms with “target” cells of the macroorganism, and promote the rapid removal of microorganisms from the gastrointestinal tract due to agglutination.

The main function of intestinal antibodies is immune rejection at the mucosal surface. It is known that IgA predominates among immunoglobulins in all secretions and in the intestinal lamina propria. Secretory IgA, which plays the role of the main “cleaner” and immunomodulator of the gastrointestinal mucosa, is retained near epithelial cells as a result of interaction with the glycocalyx, largely due to the presence of normal flora. IgA occupies a favorable position that prevents the absorption of antigens. The two-dimensional IgA molecule can function as an agglutinin, reducing bacterial adherence to enterocytes.

In the intestinal mucosa there are also cells that produce immunoglobulins of other classes, but there are much fewer of them. Thus, the ratio of plasma cells producing IgA, IgM, IgG is 20:3:1, respectively.

The most important property of the intestinal local immune system is the phenomenon of lymphocyte recycling. Sensitized by antigens (both food and infectious), lymphocytes of Peyer's patches migrate to the mesenteric lymph nodes, and from there through the lymphatic vessels through the thoracic duct and the circulatory system they are sent to the own layer of the intestinal mucosa, mainly as cells secreting IgA. This mechanism ensures the formation of lymphocyte clones and the formation of specific antibodies in areas of the mucous membrane remote from the site of primary sensitization. In the process of sensitization of plasma cells followed by cloning of lymphocytes that produce antibodies with certain properties (similar to those that acted as the matrix), not only native immunoglobulin molecules, but also active Fc- and F(ab’)2-fragments are involved.

Cellular immunity of the intestine, in contrast to the system of antibodies secreted by it, has not been studied enough. It is known that systemic cellular immune responses are rarely detected after oral exposure to antigens. Obviously, when healthy people receive harmless antigens (for example, normal flora antigens), cellular immune reactions do not develop in the intestinal mucosa.

The local intestinal immune system works as follows. Microorganisms that enter the intestinal lumen or mucous membranes are recognized by memory immunoglobulins (IgG), after which the information is transmitted to the immunocompetent cells of the mucous membrane, where plasma cells responsible for the synthesis of IgA and IgM are cloned from sensitized lymphocytes. As a result of the protective activity of these immunoglobulins, the mechanisms of immunoreactivity or immunotolerance are activated. The immune system “remembers” normal flora antigens, which is facilitated by genetic factors, as well as class G antibodies transmitted from the mother to the fetus during pregnancy, and immunoglobulins entering the baby’s gastrointestinal tract with breast milk. As a result of lymphocyte recycling and cloning, the immune response covers all mucous membranes of the gastrointestinal tract.

The regulation of immune responses of the intestinal mucosa is a complex process that can change in various situations, such as: the presence or absence of mucosal damage, maintenance of biofilm integrity and functionality, the presence of acute or chronic infections, the maturity of the immune system, the nutritional status and genetic potential of the individual . Changes in immunological reactivity may occur as a result of mucosal damage, although in this situation it is difficult to distinguish between primary and secondary effects.

The role of intestinal microflora in immune reactions

The intestinal microflora protects humans from colonization by exogenous pathogens and inhibits the growth of pathogens already present in the intestine through competition for nutrients and binding sites, as well as the production of certain pathogen growth-inhibiting substances. In addition, bacteria are involved in the implementation of immunological defense mechanisms.

It is known that one of the functions of normal flora is immunotropic, which consists in stimulating the synthesis of immunoglobulins, potentiating the mechanisms of nonspecific resistance, systemic and local immunity, properdin, complement, lysozyme, as well as stimulating the maturation of the system of phagocytic mononuclear cells and the intestinal lymphoid apparatus. Normoflora activates not only local intestinal immunity, but also the immune system of the whole organism, which is confirmed in experiments on germ-free animals. The main activities of indigenous (normal) microflora in ensuring a normal immune response: changing the immunogenicity of foreign proteins by proteolysis; decreased secretion of inflammatory mediators in the intestine; decreased intestinal permeability; direction of antigen to Peyer's patches. The same effects are realized in probiotic preparations.

Against the background of a decrease in bifidobacteria and lactobacilli, the permeability of the intestinal epithelial barrier to food macromolecules and the deficiency of secretory IgA increase. In turn, deficiency of secretory IgA can lead to the development of intestinal diseases and frequent sinubronchial infections, and ultimately to a predisposition to atopy and autoimmune diseases.

Studies conducted on animals have shown that when biocenosis is disrupted in the gastrointestinal tract, autoimmunization to the complex antigen of the intestinal wall develops, and the use of immunobiological drugs prevents this process.

Dysbiosis as immune dysfunction

The immune system regulates the balance of the intestinal biocenosis, i.e. the mechanisms of self-regulation of normal flora are controlled by the local intestinal immunity. Since any microorganism is an antigen, there must be mechanisms for the rejection of foreign microorganisms, as well as tolerance and the creation of favorable conditions for normal flora.

It is known that IgG, that is, immunoglobulins that provide immunological memory, is transmitted through the placenta from the mother to the fetus. Antibodies of classes M and A do not pass through the placenta, which explains the lack of protection of the newborn against gram-negative microorganisms (enterobacteria, salmonella). In addition, it has been proven that the first microorganisms that enter the intestines appear there during and after the birth of a child and attach to certain receptors. The process of specific adhesion of opportunistic and pathogenic microorganisms to the gastrointestinal mucosa can be blocked, among other factors, by the presence of IgA and lysozyme, which, in turn, promote adhesion to the receptors of representatives of bifido- and lactoflora.

Confirmation of the role of IgA in preventing colonization of mucous membranes by foreign microorganisms is the fact that 99% of normal flora bacteria are not covered with secretory immunoglobulins. On the contrary, enterobacteria, staphylococci, and other opportunistic and saprophytic microorganisms are completely covered with IgA. This phenomenon is based on the phenomenon of immunological tolerance to normal flora.

In newborns and young children, transient immune deficiency is a biological pattern, mainly related to humoral immunity. Children of this age group, much more often than children older than one year, experience persistent disturbances of the intestinal biocenosis, which is partly due to a deficiency of the immune system.

The physiological insufficiency of the local intestinal immune system in the first three months of a child’s life is compensated by the intake of IgA and other protective factors with human milk. When breastfeeding, a child receives up to 1.5 g of IgA every day. In children who are on artificial or early mixed feeding, i.e., deprived of the protective factors of human milk, food allergies and intestinal dysbiosis are much more likely to be observed, which is noted by most researchers in this area.

The penetration of infectious agents into the mucous membranes of the gastrointestinal tract and other organs causes a response from the local immune system in the form of an increase in the concentration of IgA, which is produced with the participation of normal flora. Accordingly, a situation may arise when a microbiological imbalance of one type will contribute to the aggravation of microecological disorders. Thus, a decrease in the amount of normal flora entails IgA deficiency, resulting in increased colonization of the mucous membranes with opportunistic pathogenic flora (OPF).

Congenital and transient anomalies of the local intestinal immune system reduce the body's resistance not so much to aggressive virulent microorganisms, but to UPF. The stability of intestinal dysbiosis is associated with them.

Almost 100% of people with acquired immunodeficiencies (as a result of radiation exposure and other immunosuppressive factors) have disturbances in the composition of the intestinal microflora, while they experience not only an increased increase in the UPF, but also a sharp decrease in normal flora, that is, the protective function of local immunity is also impaired, and immunological tolerance, which may indirectly indicate that the local immune system contributes not only to the elimination of foreign microorganisms, but also creates optimal conditions (and not just immunological tolerance) for normal flora.

Considering the significant interaction between the intestinal biocenosis and the local intestinal immune system, it is advisable to consider dysbiosis not only a microbiological, but also an immunological problem, which should be reflected in therapeutic tactics.

Immunocorrection for intestinal dysbiosis

The development of dysbiosis indicates a lack of functioning of the local intestinal immune system. Fully supporting the thesis about the secondary nature of biocenosis disorders (dysbacteriosis is always secondary and causally determined), we can assume that one of the reasons for the development of any dysbacteriosis is immunological dysfunction and, above all, insufficiency of humoral immunity.

The main remedy for the immunocorrection of dysbacteriosis is a complex immunoglobulin preparation (CIP), developed by employees of the Moscow Research Institute of Experimental Medicine named after. G. N. Gabrichevsky. The material for obtaining CIP is donor plasma from several thousand donors, so we can talk about herd immunity. KIP, unlike normal human immunoglobulin, contains immunoglobulins of three classes: 50% IgG, 25% IgM, 25% IgA. CIP is characterized by an increased content of antibodies to enterobacteria (Shigella, Salmonella, Escherichia, Proteus, Klebsiella, etc.), Pseudomonas aeruginosa, staphylococci, and rotaviruses. Thus, the CIP includes immunoglobulins of 3 classes to the main types of pathogenic and opportunistic flora. Specific antibodies contained in the CIP neutralize the effect of enteropathogenic microorganisms, which is achieved by the presence in the preparation of antibodies of the same specificity, but of different classes, promoting agglutination, neutralization and precipitation of infectious agents.

The drug is a lyophilized mixture in vials. 1 standard dose contains 300 mg of protein and trace amounts of preservatives. Administered orally, CIP is partially broken down in the stomach and duodenum into active components: Fc- and F(ab’)2-fragments, which retain the serological and antigen-binding activity of immunoglobulins. These fragments have too large a molecular weight to penetrate into the systemic circulation through the intestinal mucosa, so CIP has mainly a local effect in the lumen, on the mucous membranes and in the layer of the mucous membrane, penetrating into the bloodstream in microquantities by pinocytosis, etc. The action of CIP occurs throughout the gastrointestinal tract, but especially in the large intestine, where a large amount of lymphoid tissue (Peyer's patches) is concentrated.

To understand the mechanism of action of CIP, one should recall the basic principles of classical immunology. It is known that the most abundant IgG (75%) in the blood serum of any person has the simplest structure among antibodies and is the main carrier of immunological memory. Specific monoclonal immunoglobulins are formed in lymphoid tissue; they are synthesized by lymphocytes that have undergone differentiation due to antigen-sensitized antibodies. Despite the short lifespan of class G immunoglobulins (21-28 days), due to the differentiation of lymphocytes, immunological memory is preserved for quite a long time (often lifelong). Immunoglobulin molecules in all people have a similar structure (for example, IgG to Klebsiella is the same in everyone), and therefore are not perceived by the immune system as foreign proteins. “Foreign” antibodies introduced into the body, having reached the intestinal lymphoid tissue, are included in the formation of immunological memory along with their own, which are produced as a result of contact with the antigen. The phenomenon of lymphocyte recirculation promotes the formation of specific antibodies in areas of the mucous membrane distant from the site of primary sensitization. Therefore, immunoglobulins administered enterally not only perform the function of an immune response in the intestine, but also act as a matrix from which plasma cells with desired properties are cloned. The local intestinal immune system acquires the ability to resist those microorganisms to which antibodies are contained in the CIP. Passive immunization of a child receiving breast milk is carried out similarly through the immunoglobulins contained in it. Thus, immunocorrection with a complex immunoglobulin preparation is physiological. CIP stimulates the mechanisms of development of one's own local humoral immunity, which is especially important for children deprived of mother's milk.

In addition to its effect on intestinal immunity, KIP has a direct antimicrobial effect due to the content of antibodies of classes M and A. These immunoglobulins, by binding to complement, cause lysis of bacteria. Therefore, CIP can be used without the addition of other antibacterial drugs.

To correct microbiological disorders, CIP is prescribed in a course of 5-10 days, 1 dose 1 time per day (in the morning 30 minutes before meals). A five-day course is recommended for the following types of dysbiosis:

Dysbacteriosis with the absence of UPF in the study is compensated;

Dysbacteriosis with the amount of UPF ≤ 50%;

Extended instrumentation courses (ten-day or two five-day courses with an interval of 5 days between them - 5+5 scheme) are shown:

For any decompensated dysbacteriosis;

For dysbacteriosis with the amount of UPF > 50%).

In the described situations, prolonged courses turned out to be more effective than the traditional five-day course, which was confirmed by a special study.

In addition to CIPs, there are suppository forms in vials, as well as combinations of CIPs with interferon (Kipferon). Kipferon in suppositories has a local effect in the distal parts of the rectum and a general immunostimulating effect due to absorption in the hemorrhoidal plexus of the rectum (inferior vena cava system).

CIP in suppositories is used in children with the following indications: constipation accompanied by the development of rectal fissures; symptoms of colitis; prevention and treatment of respiratory infections in children over 1 year of age; and also together with CIP in vials, used per os, to enhance the immunostimulating effect in children with severely weakened immunity.

The course of treatment for KIP in suppositories is 5-10 days, 1/2-1 suppository once at night, after bowel movement. The child’s well-being improves during treatment or at the end of the course. The effect of using instrumentation in candles is confirmed by laboratory studies.

In addition to correcting dysbiosis, CIP is used in combination with traditional etiotropic and pathogenetic therapy for the treatment of acute intestinal infections of established or unclear etiology, especially in young children. In patients, on days 2-3, intoxication decreases, the frequency of stools decreases, its consistency improves, pathological impurities disappear, and on days 5-6, stool normalization occurs. A study of the intestinal microflora shows the sanitization of the body from the pathogen, while, unlike the use of antibiotics, a decrease in the amount of normal flora is not observed. Suppositories with CIP are indicated for the treatment of acute intestinal infections in a selected group of children (for vomiting, intolerance to oral administration, etc.).

Safety of instrumentation use

TPIs should be used with caution in children with an allergy to protein, a history of reaction to the administration of immunoglobulins, as well as in other situations fraught with the development of adverse reactions during use, and contraindications to the use of immunoglobulins.

The technology for obtaining CIP, including alcohol fractionation of serum with subsequent precipitation of the immunoglobulin fraction with polyethylene glycol, eliminates the possibility of transmission of hepatitis B viruses, HIV and other pathogenic microorganisms with the drug. In addition, donor or placental blood from which plasma is obtained for the preparation of CIP, as well as batches of the finished drug, are carefully checked. Therefore, fears of infection through the use of CPIs are not justified.

Clinically significant allergic reactions when taking CIP were observed extremely rarely. In some cases (especially when used together with bacteriophages), a short-term deterioration in well-being and an increase in symptoms that existed before treatment were noted, which is apparently associated with lysis of the UPF. Some children experienced a decrease in appetite while taking CIP, but it always recovered quickly and independently.

The use of CPI in prolonged courses did not increase the incidence of side effects compared to traditional regimens. To be on the safe side, in some cases, antihistamines can be prescribed simultaneously with taking CIP.

For questions regarding literature, please contact the editor.

Yu. A. Kopanev, Candidate of Medical Sciences Research Institute of Epidemiology and Microbiology named after. G. N. Gabrichevsky, Moscow