Normal activities human body involves maintaining conditions internal environment, which differ significantly from external environmental conditions. The area of contact between these two environments is of utmost importance for the integrity of the entire organism, therefore the structure and function of surface tissues is largely dependent on the formation of a barrier between the cells of the body and the external environment. The outside of the body is covered with skin, and the barrier function inside the body is performed by the mucous membranes that line various tubular and hollow organs. Most important have organs of the gastrointestinal, respiratory and urogenital tracts. The mucous membranes of other organs, such as the conjunctiva, are less significant.
Despite the variety of functions of various mucous membranes, they have common features buildings. Their outer layer is formed by epithelium, and the underlying layer connective tissue richly supplied with blood vessels and lymphatic vessels. Even lower there may be a thin layer of smooth muscle tissue. The skin and mucous membranes form a physical and environmental barrier that prevents pathological agents from entering the body. Their defense mechanisms, however, are radically different.
The outer layer of the skin is represented by a durable stratified keratinizing epithelium, the epidermis. There is usually little moisture on the surface of the skin, and the secretions of the skin glands prevent the proliferation of microorganisms. The epidermis is impermeable to moisture, counteracts the damaging effects 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 complex for a number of reasons. Only mucous membranes oral cavity, esophagus and anus, where the surface experiences significant physical stress, 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 skin epidermis. In the remaining mucous membranes, the epithelium is single-layered, which is necessary for it to perform specific functions.
Another specific feature of mucous membranes as a protective barrier is the moisture content of their surface. The presence of moisture creates conditions conducive to the proliferation of microorganisms and the diffusion of toxins into the body. Another significant factor is that the total surface area of the body’s mucous membranes far exceeds the surface of the skin. In only one small intestine due to numerous finger-shaped outgrowths of the intestinal wall, as well as microvilli plasma membrane epithelial cells, the surface area of the mucosa reaches 300 m2, which is more than a hundred times the surface area of the skin.
Microorganisms populate almost all areas of the mucous membranes, although their distribution and numbers are very heterogeneous and are determined by anatomical and physiological characteristics mucous membranes. The greatest species diversity of microorganisms was noted in gastrointestinal tract(Gastrointestinal tract), about 500 species are identified here. The number of microbial cells in the intestine can reach 1015, which significantly exceeds the number of the host’s own cells. On the contrary, microorganisms are normally absent on the mucous membranes of the bladder and kidneys, as well as the lower respiratory tract.
Depending on the conditions, which can vary greatly, certain microorganisms dominate in different mucous membranes. For example, in the oral cavity, a number of microorganisms are specially adapted to the anaerobic conditions of the gum pockets, while others have the ability to remain 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. Resident populations of microbes are present in the nasal cavity and pharynx. Special bacteria are also found in the choanae, and the causative agent of meningitis is detected here in approximately 5% of healthy individuals. The oral region of the pharynx contains bacteria of many types, but streptococci are quantitatively dominant here
The population of microorganisms in the gastrointestinal tract varies in composition and number depending on the section of the tract. The acidic environment of the stomach limits the proliferation of bacteria, however, even here normal conditions Lactobacilli and streptococci can be detected, which transit through the stomach. Streptococci, lactobacilli are detected in the intestines, and gram-negative bacilli 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. IN 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. Number anaerobic microorganisms in the large intestine exceeds aerobes by 100-1000 times. Microbial cells are often found in distal sections urogenital tract. The microflora of the urethra resembles the microflora of the skin. Colonization of higher parts of the tract is prevented by washing away microorganisms with urine. Bladder and the kidneys are usually sterile.
Composition of vaginal microflora healthy woman includes more than 50 species of anaerobic and aerobic bacteria and can vary depending on hormonal status. Microbial cells are often found in the distal parts of the urogenital tract. The microflora of the urethra resembles that of the skin. Colonization of higher parts of the tract is prevented by washing away microorganisms with 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 the joint evolution of their symbiosis with microorganisms. One of the important functions of microflora is trophic. For example, anaerobic intestinal microflora decomposes polysaccharides that are not hydrolyzed by their own digestive enzymes body. During the fermentation of monosaccharides with the participation of saccharolytic anaerobes of the gastrointestinal tract, short-chain fatty acid, which significantly replenish the energy needs of colon epithelial cells and other cells of the body. Impaired supply of epithelial cells with these acids is one of the links in pathogenesis ulcerative colitis and functional diseases such as irritable bowel syndrome.
An important role of intestinal microflora is 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 mucous membrane. Some of the toxins are utilized by microflora for their own needs.
It should also be mentioned that the microflora produces active metabolites 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 participates 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 function of bacterial microflora is the stimulation of intestinal motor activity, as well as the maintenance of water and ionic homeostasis in the body.
Beneficial Effects normal microflora include prevention of colonization and infection through competition with pathogens for space and nutrients. Normal resident microflora through low-molecular 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 pathogens from entering the body by forming a viscous layer that binds pathogens. Active movement of mucus along the mucosal surface promotes further removal of microorganisms. For example, in the respiratory tract, mucus moves due to the activity of the cilia of multirow epithelium, and in the intestine - due to the peristaltic activity of the latter. In some places, in the conjunctiva, oral and nasal cavities, and urogenital tract, microbes are removed from the surface of the mucous membranes by rinsing with appropriate secretions. The mucous membrane of the nasal cavity produces about half a liter of fluid during the day. The urethra is washed with a stream of urine, and the mucus secreted from the vagina helps 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 with the participation of special molecules - adhesins. To establish adhesive contact, the bacterial cell and the target cell must overcome electrostatic repulsion, since their surface molecules normally carry a negative charge. Saccharolytic bacteria have the necessary enzymatic apparatus for the cleavage of negatively charged fragments. Hydrophobic adhesive contacts between bacteria and mucosal epithelial cells are also possible. Adhesion of microorganisms to the surface of the mucosal epithelium can also be achieved with the help of fimbriae, orderly thread-like outgrowths on the surface of bacterial cells. However, the most important role is played by interactions between adhesins and mucosal epithelial cell receptors, some of which are species specific.
Despite protective function epithelium and the bactericidal effect of secretions, some pathogens still enter the body. At this stage, protection is realized through the cells of the immune system, which are rich in the connective tissue component of the mucosa. There are a lot of phagocytes here, mast cells and lymphocytes, some of which are scattered in the tissue matrix, and the other part forms aggregates, which is most clearly manifested 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 penetrate into Peyer's patches through specialized epithelial M cells. These cells are located directly above the lymphatic follicles in the intestinal and respiratory tract mucosa. The process of antigen presentation mediated by M cells becomes particularly important during lactation, when antigen-producing cells from Peyer's patches migrate into the mammary gland and secrete antibodies into the milk, thereby providing the newborn with passive immunity against pathogens with which the mother has been exposed.
In Peyer's patches of the intestine, B-lymphocytes predominate, responsible for the development humoral immunity, they make up up to 70% of the cells here. Most plasma cells in mucous membranes produce Ig A, while cells secreting Ig G and Ig M are predominantly localized in tissues that do not contain mucosal surfaces. Ig A is the main class of antibodies in secretions respiratory tract and intestinal tract. Ig A molecules in secretions are dimers connected at the tail by a protein known as the J chain, and also contain an additional polypeptide component called secretory. Ig A dimers acquire a secretory component on the surface of epithelial cells. It is synthesized by the epithelial cells themselves and is initially 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 may protect Ig A molecules from proteolysis by digestive enzymes.
Secretory Ig A in mucus acts as first line immune defense mucous membranes, neutralizing pathogens. Studies have shown that the presence of secretory Ig A correlates with resistance to infection by various pathogens of bacterial, viral and fungal nature. Another important component of the mucosal immune defense is T-lymphocytes. T cells of one of the populations contact epithelial cells 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 clusters of cells located directly under the epithelial lining of the intestine. T cells are able to move in mucosal tissues thanks to special receptors on their membranes. If an immune response develops in the gastrointestinal mucosa, T cells can travel to other mucosae, such as the lungs or nasal cavity, providing systemic protection to the body.
The interaction between the mucosal response and the body-wide immune response is important. Systemic stimulation of the immune system (eg, by injection or inhalation) has been shown to produce antibodies in the body but may not elicit 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 the internal environment of the body only when the normal relationships between the microflora and the host organism are disrupted. However, the body can use small amounts of some toxins to activate its own defense mechanisms. An integral component of the outer membrane of 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 liver phagocytes, however small part it still penetrates into the systemic circulation. The activating effect of endotoxin on cells of the immune system has been revealed, for example, macrophages in response to endotoxin produce cytokines - β- and γ-interferons.
Normal microflora is weakly immunogenic for the host due to the fact that mucosal cells are characterized by low or polarized expression of so-called toll-like receptors. The expression of these receptors may be upregulated in response to inflammatory mediators. The molecular evolution of mucosal epithelium took place under selection pressure, which contributed to a decrease 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 the result of the convergent evolution of receptors and surface molecules of microorganisms and epithelial cells. On the other hand, pathogens often use mechanisms called molecular mimicry to overcome the protective barrier of mucous membranes. A typical example mimicry may 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 these microorganisms, during the course of evolution, have developed a system that allows them to avoid the targeted antimicrobial action of the protective forces 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 nonspecific 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 ecosystem of mucous membranes from pathogenic microorganisms.
Disruption of the ecological balance in the mucous membrane, which can occur both during the course of the disease and as a result of allopathic treatment, leads to disturbances in the composition and number of microflora. For example, when treated with antibiotics, the number of some representatives of the normal anaerobic intestinal microflora can increase sharply, and they themselves can cause disease.
A change in the composition and abundance of normal microflora can make the mucous membrane more vulnerable to pathogens. Experiments on animals showed 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 in normal animals 106 microorganisms were needed for infection, only ten pathogens were sufficient in animals that were administered streptomycin
When choosing a treatment strategy, one should take into account the fact that the formation of protective mechanisms of the mucous membranes of the human body occurred over millions of years and their normal functioning depends on maintaining a delicate balance in the microflora - macroorganism ecosystem. Stimulating the body's own defenses, in tune with the basic paradigms of biological medicine, allows one to achieve therapeutic goals without destroying at the same time the complex and perfect defense mechanisms created by nature itself.
A.G. Nikonenko, Ph.D.; Research Institute of Physiology of the Academy of Sciences of Ukraine named after. A.A. Bogomolets, Kyiv
They are determined by the entry gates of the infection, the ways of its spread in the body, and the mechanisms of anti-infective resistance.
Entrance gate– the place of penetration of microbes into the macroorganism. Such gates can be:
The entrance gate can determine the nosological form of the disease. Thus, the introduction of streptococcus in the area of the tonsils causes a sore throat, through the skin - erysipelas or pyoderma, in the area of the uterus - endometritis.
Paths of spread of bacteria in the body there may be:
1) in the intercellular space (due to bacterial hyaluronidase or epithelial defects);
2) through the lymphatic capillaries - lymphogenous;
3) by blood vessels- hematogenous;
4) through the fluid of the serous cavities and the spinal canal
Mechanisms of anti-infective resistance
1. Preventing the penetration of microbes into the body.
2. Preventing the proliferation of microbes.
3. Preventing the pathogenic action of microbes.
The role of factors that inhibit the penetration of pathogenic or opportunistic bacteria is especially important. Considering the presence of protective factors of the macroorganism, the entry of an infectious agent into it does not necessarily mean the immediate development of infB. Depending on the conditions of infection and condition protective systems, infection may not develop at all or occur in the form of bacterial carriage. In the latter case, no systemic responses of the body (including immune) are detected.
Mechanisms of cell damage by microbiota
Viruses
There are no non-pathogenic viruses, therefore the term “pathogenicity” in relation to them is not usually used, and virulence is referred to as infectivity. InfP at viral infections is caused, first of all, by damage to the cells in which they multiply, and is always the interaction of two genomes - viral and cellular.
Once inside the cell, viruses cause damage in several ways:
They inhibit the functioning of cell nucleic acids or stop protein biosynthesis. Thus, polioviruses inactivate the translation of cell m-RNA and at the same time facilitate the translation of viral m-RNA.
Viral proteins are able to penetrate into cell membrane and directly damage its receptor and other integrative capabilities (HIV, measles virus, herpes virus).
Viruses can lyse cells.
Viruses can influence the cell death program (apoptosis)
Inhibition of apoptosis probably prevents apoptosis as a protective response of the body to destroy cells infected with the virus. It is also possible that the antiapoptotic effect of viruses on the cell enhances viral replication. It is possible that this effect causes the persistence of viruses in cells or promotes tumor growth of cells infected with the virus.
Viral proteins are exposed on the surface of infected cells, recognized by the immune system, and the cells are destroyed by T lymphocytes, which significantly accelerates the destruction of infected cells and, accordingly, the death of the organ or tissue consisting of these cells.
Viruses can damage antimicrobial defense cells, which can cause a secondary infectious process. For example, damage to the epithelium of the upper respiratory tract predisposes to the subsequent development of bacterial infection (Streptococcus pneumoniae and Haemophilus influenzae). The human immunodeficiency virus, damaging CD+ helper lymphocytes, thereby contributes to the emergence of opportunistic infectious processes.
Viruses, killing one type of cell, are able to destroy other cells, the fate of which depends on the first. Thus, poliovirus denervation of motor neurons causes atrophy and sometimes death of distal skeletal muscles associated with these neurons.
During virogenesis (integrative infection), viruses can cause cell proliferation and tumor transformation, as well as a number of chronic and autoimmune diseases.
Bacteria
These microbes damage the body using all their pathogenicity factors. For example, such a factor of invasiveness and aggressiveness as enzymes exert their damaging effect either by enhancing the effect of toxins, or converting protoxins into toxins, or they themselves act as toxins as a result of the formation of substances toxic to the macroorganism, such as, in particular, the enzyme urease, which hydrolyzes urea with the formation of ammonia and CO2 . Probably, the line between enzymes and toxins is very arbitrary, especially since many toxins have now been found to have enzymatic activity.
Leading role in the pathogenesis of infectious diseases bacterial origin toxins play.
Exotoxins (more correctly called protein toxins) are usually enzymes. According to the mechanism of their damaging effect on the body, they are divided into 5 groups:
| Mechanism of damaging action | Examples |
| Toxins that damage cell membranes | a-toxins of C.perfringens, hemolysin of E.coli, leukotoxin of P.haemolitica, a-toxin of S aureus and many others. etc. Form pores in the membrane, which osmotically destroys the cell or hydrolyze cell membranes enzymatically. |
| Toxins that inhibit protein synthesis in the cell | C.diphtheriae histotoxin, P.aeruginoza exotoxin A inactivate elongation factors. Stx – toxin of S. disenteriae serovar 1 and others inactivate 28 S ribosomal RNA. |
| Toxins that activate second messenger pathways | In this case, cellular responses to extracellular signals are distorted. For example, the A subunit of cholera enterotoxin inactivates the G protein of the cell membrane, which increases the activity of adenylate cyclase and, accordingly, cAMP, resulting in impaired absorption of Na + K + and water. |
| Proteases (are supertoxins) | Botulinum and tetanus neurotoxins, lethal factor of P. anthracis! Botulinum toxin causes proteolysis of proteins in neurons, which inhibits the secretion of acetylcholine and limits muscle contractions; Tetanospasmin breaks down membrane protein and synanthobrevin in neurons and blocks the secretion of inhibitory neurotransmitters - glycine and γ-aminobutyric acid, which leads to overexcitation of motor neurons and causes persistent muscle contraction. |
| Immune response activators | Toxic shock syndrome toxins (TSST-1), enterotoxins and exfoliative toxins of S.aureus, pyrogenic exotoxins of S.pyogenes directly affect antigen-presenting cells of the immune system and T-lymphocytes, which causes their massive proliferation and the formation of large numbers of lymphocytes (IL-2, γIF), monocytic (IL-1, IL-6, TNFa) and other cytokines, together capable of causing both local tissue damage and inflammation, and a generalized effect - sepsis and septic shock. |
Endotoxins (LPS)
Mechanism of action of LPS in vivo is not specific and includes the following sequence:
When entering the body, LPS is absorbed by phagocytes (leukocytes, macrophages, etc.)
These cells are activated and secrete into environment a significant amount of biologically active substances of lipid and protein nature: prostaglandins, platelet-activating factor, leukotrienes, IL, IFN, TNF-a, colony-stimulating factors, etc. Cytokines, in addition to influencing the course of inflammation, have a pronounced immunostimulating effect.
In the blood, endotoxin interacts with HDL and its binding protein. This lipoprotein-binding protein catalyzes the transfer of its monomeric form to the membrane of the target cell (monocytes, neutrophils).
Lipoprotein binding protein binds to CD14 on the cell membrane. This protein functions as a “scavenger receptor” responsible for removing endotoxin molecules from the cell surface through endocytosis and also presenting endotoxin molecules to the “true” receptor.
Other membrane proteins that act as receptors for LPS have also been described.
The damaging effect of LPS is realized with the participation of IL-1-8, TNF, PAF.
Related information.
Question 1. What is the essence of phagocytosis?
The process of absorption and digestion of microbes and other foreign substances by leukocytes is called phagocytosis. Having encountered microbes or other foreign particles, leukocytes envelop them with pseudopods, draw them in, and then digest them. Digestion lasts about one hour.
Question 2. What mechanisms prevent microbes from entering the body?
Our body has special mechanisms, preventing the penetration of microbes into it and the development of infection. Thus, 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 (connective tissue cells). Antibodies play a major role in fighting infections. These are special protein compounds (immunoglobulins) formed in the body when foreign substances enter it. Antibodies are secreted mainly by lymphocytes. Antibodies neutralize and neutralize 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.
Question 3. What are antibodies?
Antibodies are proteins produced in the human body that are involved in the development of immunity. Antibodies interact with antigens, precipitating and neutralizing them.
Question 4. What phenomenon is called immunity?
Immunity is the body's immunity to infectious diseases.
Question 5. What types of immunity are there?
There are several types of immunity. Natural immunity is developed as a result of illnesses or is inherited from parents to children (this immunity is called innate immunity). Artificial (acquired) immunity occurs as a result of the introduction of ready-made antibodies into the body.
Question 6. What is innate immunity?
Innate immunity is called when immunity is inherited from parents to children.
Question 7. What is whey?
Blood serum is blood plasma devoid of fibrinogen. Serums are obtained either by natural plasma clotting (native serum) or by precipitation of fibrinogen with calcium ions. Most of the antibodies are retained in the sera, and stability increases due to the absence of fibrinogen.
Question 8. How does a vaccine differ from serum?
Preparations made from weakened microbes are called vaccines. When a vaccine is administered, the body produces antibodies on its own, but they can also be administered in ready-made form.
Blood for therapeutic serum is taken either from a person who has suffered from this disease, or from animals that have been previously immunized.
In other words, both are methods of preventing infections. A vaccine is killed microorganisms, in response to the introduction of which the body itself produces its own antibodies. And serums are ready-made antibodies. There is no fundamental difference between them. But it is believed that serums are less likely to cause allergic reactions.
Question 9. What is the merit of E. Jenner?
And Jenner essentially made the world's first vaccination - he vaccinated a boy cowpox. A month and a half later he infected the child smallpox, and the boy did not get sick: he developed immunity to smallpox.
Question 10. What are the blood types?
There are 4 main blood groups according to the ABO system.
Blood type I (0). Blood group I is a blood group, characterized by the absence of isoantigens A and B of the AB0 system in erythrocytes.
Blood group II (A). Blood group II is blood type, characterized by the presence of isoantigen A of the AB0 system in erythrocytes.
Blood group III (B). Blood group III is blood type, characterized by the presence of isoantigen B of the AB0 system in erythrocytes.
Blood group IV (AB). Blood group IV is a blood group characterized by the presence of isoantigens A and B of the AB0 system in erythrocytes.
THINK
1. Why is it necessary to take into account the blood group and Rh factor when transfusing blood?
Infusion of incompatible blood according to the group and Rh factor causes agglutination (sticking together) of the patient's own red blood cells, which causes serious consequences - death.
2. Which blood groups are compatible and which are not?
Currently, only single-type blood transfusions are allowed.
By vital signs and in the absence of blood components of the same group according to the AB0 system (with the exception of children), transfusion of Rh-negative blood of group 0 (I) to the recipient with any other blood group in an amount of up to 500 ml is allowed.
Rh negative red blood cell mass or a suspension from donors of group A (II) or B (III), according to vital indications, can be transfused to a recipient with group AB (IV), regardless of his Rh status.
In the absence of single-group plasma, the recipient can be transfused with group AB (IV) plasma.
Microorganisms cause the development of infectious diseases and tissue damage in three ways:
Upon contact or penetration into host cells, causing their death;
By releasing endo- and exotoxins that kill cells at a distance, as well as enzymes that cause the destruction of tissue components, or by damaging blood vessels;
Provoking the development of hypersensitivity reactions that lead to tissue damage.
The first way is primarily associated with exposure to viruses.
Viral cell damage the host occurs as a result of the penetration and replication of the virus into them. Viruses have proteins on their surface that bind 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 rhinovirus binds the ICAM-1 adhesion protein on mucosal cells. shells.
One of the reasons 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 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 shell 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 virus family. Viruses also use host cell enzymes to replicate. Newly synthesized viruses are assembled as virions in the nucleus or cytoplasm and then released outside.
A viral infection may be abortifacient(with an incomplete viral replication cycle), latent(the virus is inside the host cell, for example Hegres zoster) and persistent(virions are synthesized constantly or without disruption of cell functions, for example hepatitis B).
There are 8 mechanisms for the destruction of host cells by viruses:
1) viruses can cause inhibition of DNA, RNA or protein synthesis by cells;
2) the viral protein can penetrate directly into the cell membrane, leading to its damage;
3) during viral 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) destruction of one type of cell 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 route of tissue damage in infectious diseases is mainly associated with bacteria.
Bacterial cell damage depend on the ability of bacteria to adhere to or penetrate a host cell or to secrete toxins. The adhesion of bacteria to host cells is due to the presence on their surface of hydrophobic acids that can bind to the surface of all eukaryotic cells.
Unlike viruses, which can penetrate any cell, facultative intracellular bacteria primarily infect epithelial cells and macrophages. Many bacteria attack host cell integrins—plasma membrane proteins that bind complement or extracellular matrix proteins. Some bacteria cannot penetrate host cells directly, but enter epithelial cells and macrophages through endocytosis. Many bacteria are able to multiply in macrophages.
Bacterial endotoxin is a lipopolysaccharide, which is a structural component outer shell gram-negative bacteria. The biological activity of lipopolysaccharide, manifested by the ability to induce fever, activate macrophages and induce mitogenicity of B cells, 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 body, are also known.
The third way of tissue damage during infections - the development of immunopathological reactions - is characteristic of both viruses and bacteria.
Microorganisms are able to evade immune mechanisms protection the host due to inaccessibility to the immune response; resistance and complement-associated lysis and phagocytosis; variability or loss of antigenic properties; development of specific or nonspecific immunosuppression.
Routes of human infection
Human infection with pathogenic microorganisms can only occur through damaged skin and mucous membranes of the eye, respiratory, digestive and genitourinary tract. Infection through intact skin occurs extremely rarely, since the skin is difficult to penetrate for most microorganisms. However, even the most insignificant damage to it (insect bite, needle prick, microtrauma, etc.) can cause infection. The place where the pathogen enters the human or animal body is called the entry gate of infection. If they are the mucous membrane, three types of infection are possible: reproduction of the pathogen on the surface epithelial cells; its penetration into cells with subsequent intracellular reproduction; penetration of the pathogen through cells and its spread throughout the body.
Methods of infection
Human infection occurs in one of the following ways:
1. Airborne or airborne dust.
2. Fecal-oral. The pathogen is excreted in feces or urine, and infection occurs through the mouth by consuming contaminated food or water.
3. Transmissible, i.e. through the bites of blood-sucking arthropods.
4. Contact - direct contact with a patient, convalescent, bacteria carrier or through contaminated household items, i.e. indirect contact.
5. Sexually.
6. When using non-sterile medical devices, especially syringes, etc.
7. Vertical, i.e. from mother to child through the placenta, during childbirth or immediately after it.
Dynamics of development of infectious disease.
1. Incubation period - the period from the moment of infection to the appearance of the first signs of the disease.
2. Prodromal period, or the period of precursors. It is usually characterized by nonspecific, general manifestations - weakness, fatigue, headache, general malaise, fever, etc.
3. Period of development (heyday) of the disease.
4. The period of recovery, or convalescence. Clinical recovery usually occurs earlier than pathological and bacteriological recovery.
Bacterial carriage. Very often, after either a latent infection or a previous illness, the human body is not able to completely free itself from the pathogen. In this case, a person, being practically healthy, becomes its carrier for many months or even years. Being a source of infection for other persons, bacteria carriers play an important role in the epidemiology of many diseases (typhoid fever, diphtheria, etc.), since they release their pathogens into the environment, contaminate the air, water, food products. About 5-8% of people who have been ill typhoid fever, become chronic (for a period of more than 3 months) carriers of S. typhi and serve as their main reservoir in nature.
11. Infection and infectious process. Factors of the infectious process. Types of infections - abortive, latent, dormant, typical infectious disease, atypical disease, virogeny, slow infection, bacterial carriage. Fur-we persistence.
The term infection or infectious process denotes a set of physiological and pathological regenerative and adaptive reactions that occur in a susceptible macroorganism under certain environmental conditions external environment as a result of its interaction with pathogenic or conditionally pathogenic bacteria, fungi and viruses that penetrate and multiply in it and are aimed at maintaining the constancy of the internal environment of the macroorganism (homeostasis).
The modern doctrine of infection is the recognition that the occurrence, development and outcome of infection as a process of interaction between micro- and macroorganisms depend on the properties of both participants in this competitive interaction and on the environmental conditions in which it occurs.
1. Abortive. The pathogen penetrates the body, but does not multiply in it, either due to reliable natural resistance, or acquired specific immunity that suppresses the pathogen. Thus, the infectious process is interrupted, and the pathogen sooner or later dies or is removed from the body.
2. Latent (inapparent). The pathogen penetrates the body, multiplies in it, and the macroorganism responds to it with appropriate immunobiological reactions, leading to the formation of acquired immunity and removal of the pathogen from the body. However, there are no external clinical manifestations of this infection; it occurs latently. Often, in such a latent form, people suffer from polio, brucellosis, and some viral hepatitis and other diseases.
3. Dormant infection. The asymptomatic presence of the pathogen in the body may persist for a long time after a latent infection or after a previous illness, for example pulmonary tuberculosis, which ended in the formation of a primary complex. Under the influence of conditions that reduce the body's resistance, the living microorganisms remaining in it are activated and cause disease or its relapse. Thus, pathogenic microbes are in a “dormant” state for some time. Such “dormant” microbes can enter the body from the external environment or be the result of a pathogen microbe entering a “dormant” state. suppressed in its activity, but retaining vitality and potential readiness for activation under favorable conditions. Therefore, they are called “microbes ready to emerge.” In cases where microbes “dormant” in the body are concentrated in a local limited focus, from where they can spread and cause disease, the term “focal” infection is used (for example, extinct inflammatory process in a carious tooth, in which its causative agent - streptococcus - remains in a “dormant” state for the time being).
4. Typical form of infection for this pathogen. The pathogen penetrates the body, actively multiplies in it, causing symptoms characteristic (typical) for this disease. clinical manifestations, which are also characterized by a certain cyclicity.
5. Atypical form. The pathogen penetrates the body, actively multiplies in it, the body responds with appropriate immunobiological reactions, which lead to the formation active immunity, But clinical symptoms diseases are unexpressed, erased or atypical. Most often, this is due either to the weak pathogenic properties of the pathogen, or to the high natural resistance of the body, or to effective antibacterial treatment, or to the action of all these three factors.
6. Persistent (chronic). The pathogen enters the body, multiplies in it, causes an active form of the disease, but under the influence immune systems organism and chemotherapy drugs undergoes L-transformation. Since L-forms of bacteria are not sensitive to many antibiotics and chemotherapy drugs, whose mechanism of action is associated with disruption of cell wall synthesis, as well as to antibodies, they can long time experience in the body. Returning to its original form, the pathogen restores its pathogenic properties, multiplies and causes an exacerbation (relapse) of the disease.
7. Slow infections. The pathogen penetrates the body and can remain intracellularly in the body for a long time - months, years - in a latent state. Due to a number of biological characteristics of the pathogens of slow infections, the body is not able to get rid of them, and under favorable conditions for the pathogen, it begins to multiply unhindered, the disease becomes more and more severe and, as a rule, ends in the death of the patient. Slow infections are characterized by prolonged incubation period, long-term progressive development of the disease, weak immune response and severe outcome. A typical example of a slow infection is AIDS.
8. Bacterial carriage. Very often, after either a latent infection or a previous illness, the human body is not able to completely free itself from the pathogen. In this case, a person, being practically healthy, becomes its carrier for many months or even years. Being a source of infection for other people, bacteria carriers play an important role in the epidemiology of many diseases (typhoid fever, diphtheria, etc.), since they release their pathogens into the environment and contaminate air, water, and food products. About 5-8% of people who have had typhoid fever become chronic (for more than 3 months) carriers of S. typhi and serve as their main reservoir in nature.
