How does the body defend itself against infections? Defense mechanisms against pathogens What mechanisms prevent the penetration of microbes

Immunity. A person constantly meets with numerous pathogens - bacteria, viruses. They are everywhere: in water, soil, air, on the leaves of plants, animal hair. With dust, droplets of moisture when breathing, with food, water, they can easily enter our body. But the person does not necessarily get sick. Why?

In our body there are special mechanisms that prevent the penetration of microbes into it and the development of infection. So, the mucous membranes act as a barrier through which not all microbes are able to penetrate. Microorganisms are recognized and destroyed by lymphocytes, as well as leukocytes and macrophages (cells connective tissue). Antibodies play an important role in fighting infections. These are special protein compounds (immunoglobulins) that are formed in the body when foreign substances enter it. Antibodies are secreted mainly by lymphocytes. Antibodies neutralize, neutralize the waste products of pathogenic bacteria and viruses.

Unlike phagocytes, the action of antibodies is specific, that is, they act only on those foreign substances that caused their formation.

Immunity is the body's resistance to infectious diseases. It is of several types. Natural immunity is developed as a result of past illnesses or is inherited from parents to children (such immunity is called innate immunity). Artificial (acquired) immunity occurs as a result of the introduction of ready-made antibodies into the body. This happens when a sick person is injected with the blood serum of people who have been ill or animals. You can get artificial immunity and the introduction of vaccines - cultures of weakened microbes. In this case, the body is actively involved in the production of its own antibodies. Such immunity remains for many years.

The English rural doctor E. Jenner (1749-1823) drew attention to dangerous disease- smallpox, the epidemics of which in those days devastated entire cities. He noticed that milkmaids get smallpox much less often, and if they get sick, then in mild form. He decided to find out why this is happening. It turned out that many milkmaids become infected and get sick with cowpox during work, which people endure easily. And Jenner decided on a bold experiment: he rubbed liquid from an abscess on a cow's udder into the wound of an eight-year-old boy, that is, he made the world's first vaccination - he instilled cowpox in him. A month and a half later, he infected the child with smallpox, and the boy did not get sick: he developed immunity to smallpox.

Gradually, smallpox vaccination began to be used in most countries of the world, and terrible disease was defeated.

Blood transfusion. The doctrine of blood transfusion originates from the works of W. Harvey, who discovered the laws of blood circulation. Experiments on animal blood transfusion began as early as 1638, and in 1667 the first successful blood transfusion of an animal was carried out - a young lamb, who died from repeated bloodletting - a then fashionable method of treatment. However, after the fourth blood transfusion, the patient died. Experiments on transfusion of blood to humans ceased for almost a century.

Failures led to the idea that only human blood can be transfused to a person. For the first time blood transfusion from person to person was carried out in 1819 by the English obstetrician J. Blundell. In Russia, the first successful blood transfusion from person to person was made by G. Wolf (1832). He saved a woman who was dying after childbirth from uterine bleeding. Scientifically based blood transfusion became possible only after the creation of the doctrine of immunity (I. I. Mechnikov, P. Ehrlich) and the discovery of blood groups by the Austrian scientist K. Landsteiner, for which he was awarded the Nobel Prize in 1930.

Human blood types. The concept of blood groups was formed at the turn of the 19th-20th centuries. In 1901 Austrian researcher K. Landsteiner investigated the problem of blood compatibility during transfusion. Mixing erythrocytes with blood serum in the experiment, he found that with some combinations of serum and erythrocytes, agglutination (gluing) of erythrocytes is observed, while others do not. The process of agglutination occurs as a result of the interaction of certain proteins: antigens present in erythrocytes - agglutinogens and antibodies contained in plasma - agglutinins. Upon further study of the blood, it turned out that the main agglutinogens of erythrocytes were two agglutinogens, which were named A and B, and in the blood plasma - agglutinins a and p. Depending on the combination in the blood of those and others, four blood groups are distinguished.

As it was established by K. Landsteiner and Ya. Jansky, in the blood erythrocytes of some people there are no agglutinogens at all, but in the plasma there are agglutinins a and p (group I), in the blood of others only agglutinogen A and agglutinin p (group II) are present, in the third - only agglutinogen B and agglutinin a (group III), erythrocytes of the fourth contain agglutinogens A and B, do not have agglutinins (group IV).

If, during transfusion, the blood groups of the donor and the patient (recipient) are selected incorrectly, then a threat is created for the recipient. Once in the patient's body, red blood cells stick together, which leads to blood clotting, blockage of blood vessels and death.

Rh factor. Rh factor - a special protein - agglutinogen contained in the blood of humans and monkeys - rhesus monkeys (hence the name), was discovered in 1940. It turned out that 85% of people have this agglutinogen in their blood, they are called Rh-positive (Rh + ), and y 15% of people do not have this protein in their blood, they are called Rh-negative (Rh-). After a transfusion of Rh-positive blood to an Rh-negative person, specific antibodies are produced in the blood of the latter for a foreign protein. So reintroduction the same person with Rh-positive blood can cause erythrocyte agglutination and severe shock.

This virus is not spread by sneezing, coughing and kissing, through water, shaking hands, sharing a plate and a spoon. There are no known cases of human-to-human transmission of the virus by a mosquito or flea bite. It is believed that HIV infection requires contact with blood, semen, cerebrospinal fluid or breast milk the patient, and this contact must take place in the body of the infected person. HIV is mainly transmitted by injection with a needle in which the infected HIV blood, when such blood is transfused, from an infected mother to an infant through blood or milk, during any sexual contact. AT last case the likelihood of infection naturally increases in cases where the mucous membrane or skin at the point of contact is damaged.

Test your knowledge

1. What is the meaning of phagocytosis?
2. What mechanisms prevent the penetration of microbes into the body?
3. What are antibodies?
4. What phenomenon is called immunity?
5. What are the types of immunity?
6. What is innate immunity?
7. What is serum?
8. How is a vaccine different from a serum?
9. What is the merit of E. Jenner?
10. What are the blood types?

Think

1. Why is it necessary to take into account the group and Rh factor of blood when transfusing blood?
2. Which blood types are compatible and which are not?

The outer membranes of our body prevent the penetration of microbes into the body. Microbes that enter the body are destroyed by phagocytes. Immunity is the resistance of the body to infectious diseases. There are natural and artificial immunity. Presence or absence in human blood certain antigens and antibodies distinguish four blood groups. Depending on the presence of an antigen called “Rh factor” in red blood cells, people are divided into Rh-positive and Rh-negative.

"Cardiovascular system" - The wall of the heart consists of three layers - epicardium, myocardium and endocardium. Pavlov Nikita is engaged in judo, karate, swimming, table hockey. Harvard step test. Duration recovery period(in seconds). Conclusion. Possesses automaticity. Located in chest retrosternally. The work of the heart is described by mechanical phenomena (suction and expulsion).

"The structure of the heart" - Determine the right and left halves of the heart. The structure of the heart of reptiles. The structure of the mammalian heart. pulmonary artery. Left ventricle. Aristotle. The structure of the human heart. What is the significance of the fluid secreted by the formation covering the heart? Locate the flap valves in the pictures. Locate the vessels that flow into the right and left halves of the heart.

"Lesson of the Circulatory Organs" - Acquaintance with the techniques of self-observation of activities of cardio-vascular system; Blood vessels. Which statements are true. The study of the human circulatory system. Excessive mental stress does not affect the heart - vascular system. Biology lesson in 8th grade. A heart. capillaries.

"Blood lesson" - 3. Theme of the lesson. Hb+O2. Insoluble fibrin thrombus is about 400 thousand. The mechanism for the performance of their functions by erythrocytes. 1. Platelets 2. Ca 2+ ions 3. blood serum 4. to the fourth and to itself 5. recipient. 4. Summing up. Lesson plan. Fibrin. A person who receives a blood transfusion is called……….. Rh factor.

"Human blood" - III blood group. There are agglutinogens A and B, no agglutinins. 1667 - a lamb's blood was transfused to a sick young man. Presentation for a biology lesson on the topic: "Immunity" Grade 8. Special mechanisms that prevent the penetration of microbes. Special antibodies are produced. Repeated transfusion of Rh-positive blood.

"Blood type" - IV (AB) - the youngest. They respond to stress with panic. The oldest is group I (00). Smart, inventive, purposeful, sensitive and aggressive at the same time. I group. Blood types in Russia. Blood map. Tasks: Obviously, as a result of the sexual activity of the nomads.

There are 16 presentations in total in the topic

The following protective mechanisms are involved in the fight against microorganisms: natural barriers - mucous membranes of the nose, throat, respiratory tract, skin; non-specific mechanisms - attraction certain types leukocytes and an increase in body temperature (fever), as well as specific mechanisms, in particular antibodies.

As a rule, if a microbe penetrates natural barriers, non-specific and specific defense mechanisms destroy it before it begins to multiply.

natural barriers

Normally, intact skin prevents the invasion of microbes into the body, and the vast majority of them overcome this barrier only as a result of injury or burns, insect bites, etc. True, there are exceptions: infection with human papillomavirus that causes warts.

Other effective natural barriers include mucous membranes, in particular those of the respiratory tract and intestines. Normally, the mucous membranes are covered with mucus, which prevents the penetration of microbes.

For example, the mucous membranes of the eyes are irrigated with tear fluid containing an enzyme called lysozyme. It attacks bacteria, helping to protect the eyes from them. The respiratory tract effectively cleans the air entering them. In the sinuous nasal passages, on their walls, covered with mucus, many foreign substances that enter with the air, including microbes, are retained. If the microorganism reaches the lower respiratory tract (bronchi), the coordinated movement of cilia (like hairs) covered with mucus removes it from the lungs. Coughing also contributes to the removal of microorganisms.

The gastrointestinal tract has a number of effective barriers: stomach acid, pancreatic enzymes, bile and intestinal secretions have antibacterial activity. The contractions of the intestines (peristalsis) and the normal shedding of the cells lining the intestines help remove harmful microorganisms.

As for the organs of the urinary system, in men they are protected from bacteria due to their large length. urethra(approximately 25 cm). The exception is when bacteria are introduced there with surgical instruments. The woman's vagina is protected by its acidic environment. The flushing effect during emptying of the bladder is another defense mechanism in both sexes.

People with impaired defense mechanisms are more susceptible to certain infectious diseases / see. p. For example, with low acidity gastric juice increased susceptibility to tuberculosis and salmonellosis. To maintain the body's defense mechanisms, the balance of various types of microorganisms of the opportunistic intestinal flora is important. Sometimes, under the influence of an antibiotic, which is taken to treat an infection that is not associated with the intestines, the balance of opportunistic flora is disturbed, as a result of which the number of pathogens increases.

Non-specific defense mechanisms

Any damage, including the invasion of pathogens, is accompanied by inflammation. It mobilizes some of the body's defenses towards the site of injury or infection. With the development of inflammation, the blood supply increases, and white blood cells can more easily pass from the blood vessels to the inflamed area.

The number of leukocytes in the blood also increases; the bone marrow releases more cells from the depot and intensively synthesizes new ones. Neutrophils that appear at the site of inflammation begin to capture microorganisms and try to keep them in a limited space / cm. p. 665/. If this fails, monocytes, which have an even greater ability to capture microorganisms, rush to the site of damage in increasing numbers. However, these non-specific defense mechanisms may not be sufficient when in large numbers microbes or due to the influence of other factors, such as air pollution (including tobacco smoke), which reduce the strength of the body's defense mechanisms.

Increase in body temperature

An increase in body temperature (fever) to more than 37 ° C is actually a protective reaction of the body to the introduction of pathogens or other damage. Such a reaction enhances the body's defense mechanisms, causing only relatively little discomfort in a person.

Normally, body temperature fluctuates throughout the day. Its lowest indicators (level) are noted at 6 o'clock, and the highest - at 16-18 o'clock. Although normal temperature bodies usually consider 36.6 ° C, upper bound the norm at 6 o'clock is 36.0 ° C, and at 16 o'clock - 36.9 ° C.

The part of the brain called the hypothalamus regulates body temperature, and therefore the increase in temperature is a consequence of the regulating influence of the hypothalamus. Body temperature rises to a new high level by redistribution of blood from the surface of the skin to internal organs resulting in reduced heat loss. Trembling may occur, indicating an increase in heat production as a result of muscle contractions. Changes in the body to conserve and produce more heat continue until the blood reaches the new higher temperature at the hypothalamus. This temperature is then maintained in the usual manner. Later, when she returns to normal level The body eliminates excess heat through sweating and redistribution of blood to the skin. With a decrease in body temperature, chills may develop.

Body temperature can rise every day and return to normal. In other cases, the temperature increase may be relapsing, that is, it changes but does not return to normal.

In severe infectious diseases in some cases, such as alcoholics, the elderly and young children, body temperature may decrease.

Substances that cause an increase in body temperature are called pyrogens. They can form inside the body or come from outside. Pyrogens formed outside the body include microorganisms and the substances they produce, such as toxins.

In fact, pyrogens that enter the body from outside cause an increase in body temperature, stimulating the formation of its own pyrogens in the body. Pyrogens inside the body are usually produced by monocytes. However, an infectious disease is not the only cause of an increase in body temperature; temperature may rise due to inflammation, malignancy, or allergic reaction.

Causes of an increase in body temperature

Usually, an increase in body temperature has an obvious cause. It could be, for example, the flu or pneumonia. But sometimes the cause is difficult to find, for example, when the membrane is infected heart valve(septic endocarditis). When a person has a fever of at least 38.0°C and a thorough examination does not reveal the cause, a doctor may label the condition as a fever of unknown origin.

Such cases include any disease accompanied by an increase in body temperature, but the most common causes in adults are infectious diseases, conditions associated with the formation of antibodies against the body's own tissues ( autoimmune diseases), and malignant tumors(especially leukemias and lymphomas).

To determine the cause of an increase in body temperature, the doctor asks the patient about existing and previous symptoms and diseases, about medications taken, about possible contacts with infectious patients, about recent travel, and so on, since the nature of the increase in temperature usually does not help in diagnosis. However, there are some exceptions. For example, malaria typically has a fever that occurs every other day or every third day.

Information about recent travel, especially abroad, or contact with certain materials or animals may provide clues to the diagnosis. A person who has consumed contaminated water (or ice made from contaminated water) may become ill typhoid fever. A worker in a meat packing plant can become infected with brucellosis.

After clarifying such questions, the doctor conducts full examination to find the source of the infection and other signs of illness. Depending on the degree of fever and the patient's condition, the examination may be performed on an outpatient basis or in a hospital. A blood test can detect antibodies against microorganisms. You can also do blood cultures on various nutrient media; determine the number of leukocytes in a blood test. The increased content of certain antibodies helps to identify the "guilty" microorganism. An increase in white blood cells usually indicates an infection.

Ultrasound examination (ultrasound), CT scan(CT) and magnetic resonance imaging (MRI) also help in the diagnosis. Scanning with radioactively labeled leukocytes can be used to identify the focus of inflammation. As leukocytes enter areas of accumulation infectious agents, and the injected leukocytes have a radioactive marker, the scan helps to detect the infected area. If the scan results are negative, the doctor may take a biopsy of liver tissue, bone marrow or other “suspected” organ, followed by examination under a microscope.

Whether to reduce elevated body temperature

The positive effect of raising body temperature has already been mentioned. However, the question of the need to reduce it causes some controversy. So in a child who previously had an attack of convulsions due to an increase in body temperature (febrile convulsions), it should be reduced.

An adult with heart or lung disease requires the same approach, because heat The body's oxygen demand increases by 7% for every degree above 36.6°C. An increase in body temperature can also cause brain dysfunction. Medicines that can lower body temperature are called antipyretics. The most widely used and effective antipyretics are paracetamol and non-steroidal anti-inflammatory drugs such as aspirin. However, aspirin should not be used in children and adolescents to lower body temperature, as it increases the risk of developing Reye's syndrome, which can be fatal.

Specific defense mechanisms

Infection unleashes all power immune system. The immune system produces substances that specifically attack pathogens. For example, antibodies attach to a microorganism and help immobilize it. Antibodies can directly destroy microorganisms or make it easier for leukocytes to "work" to recognize and destroy them. The immune system can also send out cells called killer T cells (a type of white blood cell) that specifically attack the pathogen. The body's natural defense mechanisms are assisted by anti-infective drugs, such as antibiotics, antifungals, or antiviral agents. However, if a person's immune system functions are significantly impaired, these drugs are often ineffective.

Microorganisms cause development infectious disease and tissue damage in three ways:

Upon contact or penetration into host cells, causing their death;

Through the release of endo- and exotoxins that kill cells at a distance, as well as enzymes that cause the destruction of tissue components, or damaging blood vessels;

Provoking the development of hypersensitivity reactions that lead to tissue damage.

The first way is associated primarily with exposure to viruses.

Viral cell damage the host arises as a result of the penetration and replication of the virus in them. Viruses have proteins on their surface that bind to specific protein receptors on host cells, many of which perform important functions. For example, the AIDS virus binds a protein involved in antigen presentation by helper lymphocytes (CD4), the Epstein-Barr virus binds the complement receptor on macrophages (CD2), the rabies virus binds acetylcholine receptors on neurons, and rhinoviruses bind the ICAM-1 adhesion protein on mucosal cells. shells.

One reason for the tropism of viruses is the presence or absence of receptors on host cells that allow the virus to attack them. Another reason for the tropism of viruses is their ability to replicate within certain cells. The virion or its portion, containing the genome and special polymerases, penetrates into the cytoplasm of cells in one of three ways:

1) by translocation of the entire virus through the plasma membrane;

2) by fusion of the virus envelope with the cell membrane;

3) with the help of receptor-mediated endocytosis of the virus and its subsequent fusion with endosome membranes.

In the cell, the virus loses its envelope, separating the genome from other structural components. The viruses then replicate using enzymes that are different for each of the virus families. Viruses also use host cell enzymes to replicate. The newly synthesized viruses are assembled as virions in the nucleus or cytoplasm and then released to the outside.

Viral infection may be abortive(with an incomplete viral replication cycle), latent(the virus is inside the host cell, for example hegres zoster) and persistent(virions are synthesized continuously or without disruption of cell functions, such as hepatitis B).

There are 8 mechanisms for the destruction of macroorganism cells by viruses:

1) viruses can cause inhibition of DNA, RNA or protein synthesis by cells;

2) the viral protein can be introduced directly into cell membrane leading to damage;

3) in the process of virus replication, cell lysis is possible;

4) with slow viral infections, the disease develops after a long latent period;

5) host cells containing viral proteins on their surface can be recognized by the immune system and destroyed with the help of lymphocytes;

6) host cells can be damaged as a result of a secondary infection that develops after a viral one;

7) the destruction of cells of one type by a virus can lead to the death of cells associated with it;

8) viruses can cause cell transformation leading to tumor growth.

The second way of tissue damage in infectious diseases is associated mainly with bacteria.

Bacterial cell damage depend on the ability of bacteria to adhere to or enter the host cell or release toxins. The adhesion of bacteria to host cells is due to the presence on their surface of hydrophobic acids capable of binding to the surface of all eukaryotic cells.

Unlike viruses that can invade any cell, facultative intracellular bacteria mainly infect epithelial cells and macrophages. Many bacteria attack host cell integrins - proteins plasma membrane that bind complement or extracellular matrix proteins. Some bacteria cannot directly penetrate host cells, but enter epithelial cells and macrophages by endocytosis. Many bacteria are able to multiply in macrophages.

Bacterial endotoxin is a lipopolysaccharide, which is a structural component of the outer shell of gram-negative bacteria. The biological activity of lipopolysaccharide, manifested by the ability to cause fever, activate macrophages and induce B-cell mitogenicity, is due to the presence of lipid A and sugars. They are also associated with the release of cytokines, including tumor necrosis factor and interleukin-1, by host cells.

Bacteria secrete various enzymes (leukocidins, hemolysins, hyaluronidases, coagulases, fibrinolysins). The role of bacterial exotoxins in the development of infectious diseases is well established. The molecular mechanisms of their action, aimed at destroying the cells of the host organism, are also known.

The third way of tissue damage during infections - the development of immunopathological reactions - is characteristic of both viruses and bacteria.

Microorganisms can escape immune mechanisms protection host due to inaccessibility to the immune response; resistance and complement-related lysis and phagocytosis; variability or loss of antigenic properties; development of specific or nonspecific immunosuppression.

normal activity human body involves maintaining the conditions of the internal environment, which are significantly different from the conditions of the external environment. The area of ​​contact between these two media is of paramount importance for the integrity of the whole organism, therefore the structure and function of surface tissues is largely subordinated to the formation of a barrier between the cells of the organism and the external environment. Outside, the body is covered with skin, and the mucous membranes that line various tubular and hollow organs perform the function of a barrier inside the body. The most important are the organs of the gastrointestinal, respiratory and urogenital tracts. Less significant are the mucous membranes of other organs, such as the conjunctiva.

Despite the variety of functions of various mucous membranes, they have common features buildings. Their outer layer is formed by the epithelium, and the underlying layer of connective tissue is abundantly supplied with blood and lymphatic vessels. Even lower may be thin layer smooth muscle tissue. The skin and mucous membranes form a physical and environmental barrier that prevents the penetration of pathological agents into the body. Their defense mechanisms, however, are radically different.

The outer layer of the skin is represented by a strong stratified keratinized epithelium, the epidermis. On the surface of the skin, as a rule, there is little moisture, and the secrets of the glands of the skin prevent the reproduction of microorganisms. The epidermis is impervious to moisture, counteracts the damaging effect of mechanical factors and prevents the penetration of bacteria into the body. The task of maintaining the protective properties of mucous membranes is much more difficult for a number of reasons. Only mucous oral cavity, esophagus and anus, where the surface experiences significant physical exercise, as well as the vestibule of the nasal cavity and the conjunctiva, have several layers of epithelium and its structure to a certain extent resembles that of the epidermis of the skin. In the rest of the mucous membranes, the epithelium is single-layered, which is necessary for them to perform specific functions.

Another specificity of the mucous membranes as a protective barrier is the moisture content of their surface. The presence of moisture creates conditions conducive to the reproduction of microorganisms and the diffusion of toxins into the body. An important factor is the fact that the total surface area of ​​the mucous membranes of the body is much greater than the surface of the skin. In just one small intestine due to numerous finger-like outgrowths of the intestinal wall, as well as microvilli of the plasma membrane of epitheliocytes, the surface area of ​​the mucosa reaches 300 m2, which is more than a hundred times greater than the surface area of ​​the skin.

Microorganisms inhabit almost all areas of the mucous membranes, although their distribution and abundance are very heterogeneous and are determined by anatomical and physiological characteristics mucous membranes. The greatest species diversity of microorganisms was noted in the gastrointestinal tract (GIT), about 500 species are detected here. The number of microbial cells in the intestine can reach 1015, which is much higher than the number of the host's own cells. On the contrary, on the mucous membranes of the bladder and kidneys, as well as the lower parts of the respiratory tract, microorganisms are normally absent.

Depending on the conditions, which can vary greatly, certain microorganisms dominate in various mucous membranes. For example, in the oral cavity, a number of microorganisms are specially adapted to the anaerobic conditions of gum pockets, while others have the ability to stay on the surface of the teeth. Fungi and protozoa are also found here.

The microorganisms present in the upper respiratory tract are similar to those in the oral cavity. There are resident populations of microbes in the nasal cavity and pharynx. Special bacteria are also found in the choanae, and the causative agent of meningitis is detected here in about 5% of healthy individuals. The oral region of the pharynx contains bacteria of many species, however, in quantitative terms, streptococci dominate here.

The population of microorganisms in the gastrointestinal tract varies in composition and abundance depending on the section of the tract. The acidic environment of the stomach limits the growth of bacteria, however, even here in normal conditions you can find lactobacilli and streptococci that transit through the stomach. In the intestine, streptococci, lactobacilli are detected, and Gram-negative rods may also be present. The density and diversity of microflora increases as you move along the gastrointestinal tract, reaching a maximum in the large intestine. AT colon bacteria make up about 55% of the solid content. Bacteria of 40 species are constantly present here, although representatives of at least 400 species can be identified. The number of anaerobic microorganisms in the large intestine exceeds aerobes by 100-1000 times. Microbial cells are often found in the distal urogenital tract. The microflora of the urethra resembles the microflora of the skin. Colonization of the higher parts of the tract is prevented by the washing out of microorganisms in the urine. Bladder and kidneys are usually sterile.

The composition of the microflora of the vagina healthy woman includes more than 50 types of anaerobic and aerobic bacteria and may vary depending on the hormonal status. Microbial cells are often found in the distal urogenital tract. The microflora of the urethra resembles that of the skin. Colonization of the higher parts of the tract is prevented by the washing out of microorganisms in the urine. The bladder and kidneys are usually sterile.

The normal microflora of the mucous membranes is in a state of symbiosis with the body and performs a number of important functions. Its formation took place over millions of years, and therefore the evolution of mucous membranes is more correctly considered as a joint evolution of their symbiosis with microorganisms. One of the important functions of the microflora is trophic. For example, anaerobic intestinal microflora decomposes polysaccharides that are not hydrolyzed by the body's own digestive enzymes. During the fermentation of monosaccharides with the participation of saccharolytic anaerobes of the gastrointestinal tract, short-chain fatty acids are formed, which largely replenish the energy needs of colon epithelial cells and other cells of the body. Violation of the provision of epithelial cells with these acids is one of the links in the pathogenesis ulcerative colitis and functional diseases such as irritable bowel syndrome.

An important role of the intestinal microflora is the detoxification of the body. Together with indigestible carbohydrates, the microflora forms an enterosorbent with a huge adsorption capacity, which accumulates most of the toxins and removes them from the body along with the intestinal contents, preventing direct contact of a number of pathogenic agents with the mucosa. Some of the toxins are utilized by the microflora for their own needs.

We should also mention the formation of active metabolites by the microflora that can be used by the human body - γ-aminobutyric acid, putrescine and other compounds. The intestinal microflora supplies the host with B vitamins, vitamin K, and is involved in the metabolism of iron, zinc and cobalt. For example, the source of 20% of the essential amino acid lysine that enters the human body is the intestinal microflora. Another important feature bacterial microflora is the stimulation of the motor activity of the intestine, as well as the maintenance of water and ionic homeostasis of the body.

beneficial effects normal microflora include preventing colonization and infection by competing with pathogens for space and nutrients. Normal resident microflora, through low molecular weight metabolites, as well as special antimicrobial substances, suppresses the vital activity of a number of pathogenic microorganisms

One of the main defense mechanisms mucous membrane is the moistening of its surface with mucus, which is produced either by individual cells or by specialized multicellular glands. Slime plays important role in preventing the penetration of pathogens into the body, forming a viscous layer that binds pathogens. Active movement of mucus along the surface of the mucosa contributes to the further removal of microorganisms. For example, in the respiratory tract, mucus moves due to the activity of the cilia of the multilayered epithelium, and in the intestine - due to the peristaltic activity of the latter. In some places, in the conjunctiva, oral and nasal cavities, the urogenital tract, microbes are removed from the surface of the mucous membranes by flushing with appropriate secrets. The mucous membrane of the nasal cavity produces about half a liter of fluid during the day. The urethra is flushed with urine, and the mucus secreted from the vagina helps to remove microorganisms.

An important factor in maintaining balance in the microflora-macroorganism ecosystem is adhesion, through which the body controls the number of bacteria. The mechanisms of adhesion are very diverse and include both nonspecific and specific interactions involving special molecules - adhesins. To establish adhesive contact, the bacterial cell and the target cell must overcome the electrostatic repulsion, since their surface molecules normally carry a negative charge. Saccharolytic bacteria possess the necessary enzymatic apparatus for cleavage of negatively charged fragments. Hydrophobic adhesive contacts between bacteria and mucosal epitheliocytes are also possible. The adhesion of microorganisms to the surface of the mucosal epithelium can also be carried out with the help of fimbriae, orderly arranged thread-like outgrowths on the surface of bacterial cells. However, interactions between adhesins and mucosal epitheliocyte receptors, some of which are species-specific, play the most important role.

Despite the protective function of the epithelium and the bactericidal action of secretions, some pathogens still enter the body. At this stage, protection is realized due to the cells of the immune system, which are rich in the connective tissue component of the mucosa. There are many phagocytes, mast cells and lymphocytes, some of which are dispersed in the tissue matrix, and the other part forms aggregates, which is most pronounced in the tonsils and appendix. Aggregates of lymphocytes are numerous in ileum where they are called Peyer's patches. Antigens from the intestinal lumen can enter Peyer's patches through specialized epithelial M cells. These cells are found directly above the lymphatic follicles in the intestinal mucosa and respiratory tract. The process of antigen presentation mediated by M cells becomes especially important during lactation, when antigen-producing cells from Peyer's patches migrate to the mammary gland and secrete antibodies into milk, thus providing the newborn with passive immunity against pathogens with which the mother has come into contact.

Peyer's patches of the intestine are dominated by B-lymphocytes responsible for the development humoral immunity, they make up to 70% of the cells here. Most plasma cells in the mucosa produce Ig A, while the cells that secrete Ig G and Ig M are predominantly localized in tissues that do not contain mucous surfaces. Ig A is the main class of antibodies in respiratory secretions and intestinal tract. The IgA molecules in the secretions are dimers connected at the tail by a protein known as the J chain and also contain an additional polypeptide component called the secretory. Ig A dimers acquire a secretory component on the surface of epitheliocytes. It is synthesized by the epithelial cells themselves and is first exposed on their basal surface, where it serves as a receptor for binding Ig A from the blood. The resulting complexes of Ig A with the secretory component are absorbed by endocytosis, pass through the cytoplasm of the epithelial cell and are brought to the surface of the mucosa. In addition to its transport role, the secretory component possibly protects Ig A molecules from proteolysis by digestive enzymes.

Secretory Ig A in mucus acts as first line immune protection mucous membranes, neutralizing pathogens. Studies have shown that the presence of secretory Ig A correlates with resistance to infection by various bacterial, viral and fungal pathogens. T-lymphocytes are another important component of the mucosal immune defense. T cells from one of the populations contact epitheliocytes and exert a protective effect by killing infected cells and attracting others. immune cells to fight the pathogen. Interestingly, the source of these lymphocytes in mice are cell clusters directly under the intestinal epithelial lining. T cells are able to move in mucosal tissues due to special receptors on their membranes. If an immune response develops in the gastrointestinal mucosa, T cells can migrate to other mucosal surfaces, such as the lungs or nasal cavity, providing systemic defenses.

The interaction between the mucosal response and the bodywide immune response is important. It has been shown that systemic stimulation of the immune system (for example, by injection or through Airways) leads to the production of antibodies in the body, but may not cause a mucosal response. On the other hand, stimulation of the mucosal immune response can lead to the mobilization of immune cells both in the mucosa and throughout the body.

Low molecular weight toxins enter internal environment organism only in case of violation of the normal ratios of microflora and the host organism. However, the body can use small amounts of some toxins to activate the appropriate defense mechanisms. integral component outer membrane gram-negative bacteria, endotoxin, entering the bloodstream in significant quantities, causes a number of systemic effects that can lead to tissue necrosis, intravascular coagulation and severe intoxication. Normally, most of the endotoxin is eliminated by phagocytes of the liver, but a small part of it still penetrates into the systemic circulation. The activating effect of endotoxin on the cells of the immune system was revealed, for example, macrophages in response to endotoxin produce cytokines - β- and γ-interferons.

The normal microflora is weakly immunogenic for the host due to the fact that mucosal cells are characterized by low or polarized expression of the so-called toll-like receptors. The expression of these receptors may be upregulated in response to inflammatory mediators. The molecular evolution of the mucosal epithelium has been driven by selection pressure, which has contributed to a reduction in the body's response to commensal bacteria while maintaining the ability to respond to pathogenic microorganisms. In other words, the relationship between normal microflora and mucous membranes can be explained as a result of the convergent evolution of receptors and surface molecules of microorganisms and epitheliocytes. On the other hand, pathogens often use mechanisms to overcome the protective barrier of mucous membranes, combined under the name of molecular mimicry. A typical example of mimicry can be the presence on the outer membrane of group A streptococci of the so-called M-proteins, which in their structure resemble myosin. It is obvious that in the course of evolution these microorganisms have developed a system that allows them to avoid directed antimicrobial action defenses of the human body. It can be concluded that the protective mechanisms of the mucous membrane include many factors and are the product of the joint activity of the macroorganism and microflora. Both non-specific protective factors (pH, redox potential, viscosity, low-molecular metabolites of microflora) and specific ones - secretory Ig A, phagocytes and immune cells - act here. Together, "colonization resistance" is formed - the ability of microflora and macroorganism in cooperation to protect the mucosal ecosystem from pathogenic microorganisms.

Violation of the ecological balance in the mucous membrane, which can occur both in the course of the disease and as a result of allopathic treatment, leads to disturbances in the composition and number of microflora. For example, during treatment with antibiotics, the number of some representatives of the normal anaerobic intestinal microflora can increase dramatically, and they themselves can cause disease.

Changes in the composition and abundance of normal microflora can make the mucous membrane more vulnerable to pathogens. In animal experiments, it was shown that inhibition of the normal microflora of the gastrointestinal tract under the influence of streptomycin made it easier to infect animals with streptomycin-resistant strains of salmonella. Interestingly, while 106 microorganisms were needed for infection in normal animals, only ten pathogens were sufficient in animals that were injected with streptomycin.

When choosing a treatment strategy, one should take into account the fact that the formation of the protective mechanisms of the mucous membranes of the human body took place over millions of years and their normal functioning depends on maintaining a delicate balance in the microflora-macroorganism ecosystem. Stimulation of the body's own defenses, consonant with the basic paradigms of biological medicine, allows you to achieve therapeutic goals without destroying at the same time the complex and perfect defense mechanisms created by nature itself.

A.G. Nikonenko, PhD; Research Institute of Physiology of the Academy of Sciences of Ukraine named after A.A. Bogomolets, Kyiv