Immunity is understood as a set of processes and mechanisms that provide the body with the constancy of the internal environment from all genetically alien elements of exogenous and endogenous nature. Not specific factors resistance are manifestations of innate immunity. Allocate: mechanical barriers(skin, mucous membranes), humoral factors(immunocytokines, lysozyme, beta-lysines, properdin protein system, acute phase proteins) and cellular factors(phagocytes, natural killer cells). Unlike immunity, nonspecific resistance is characterized by:
1) Lack of a specific response to certain antibodies;
2) The presence of both inducible and non-inducible defense factors;
3) Lack of the ability to preserve memory from primary contact with the antigen.
The main cellular effector cells in the destruction of microbes are phagocytes (neutrophils, macrophages). However, the functions of phagocytes are not limited only to the killig of a foreign particle. Phagocyte discharges 3 main groups of functions:
1) Protective(actually phagocytosis)
2) Representing- macrophage presents AG to lymphocytes in the system of cell cooperation
3) Secretory- produces more than 60 active mediators, including IL-1.8; reactive oxygen species, metabolic products of arachidonic acid, etc.
With the development of insufficient activity of any of the factors of nonspecific resistance, an immunodeficiency state develops, and therefore it is necessary to have an idea of ways to assess the functional activity of each of the above components.
Scheme 1. Basic methods for assessing the various stages of phagocytosis.
1. Take into account the results of sowing of opened animals. Calculate the total contamination in different sectors, fill in the table of contamination of different organs and tissues of the experimental animal in a notebook.
2. Describe the colony (of the teacher's choice) according to the standard scheme (see the topic 'Bacteriological research method').
3. Prepare smears and color them according to Gram. Micoscopy, characterize the morphological picture.
4. To study the picture of incomplete phagocytosis in finished preparations.
5. To disassemble the scheme of setting up the phagocytosis experiment.
6. Dismantle the scheme of staging the opsono-phagocytic reaction.
Control questions:
1. List the main groups of nonspecific resistance factors.
2. Describe the anatomical barriers of nonspecific resistance.
3. What are the main differences between nonspecific resistance and immunity.
4. Describe the humoral factors of nonspecific resistance (lysozyme, immunocytokines, complement, beta-lysines, properdin system, acute phase proteins)
5. The complement system: structure, functions, types of activation?
6. What cellular factors of nonspecific resistance do you know?
7. Describe the stages of phagocytosis.
8. What are the forms of phagocytosis.
9. What are the mechanisms of phagocytosis.
10. Describe the main forms of free radicals.
11. What is the phagocytic index and phagocytic number. Assessment methods.
12. What methods can be used to additionally assess the activity of a phagocyte?
13. Method for assessing intracellular killing: clinical significance, staging.
14. Essence of opsonization. Phagocytic-opsonic index.
15. NBT test: setting, clinical significance.
16. The value of antilysozyme, anti-complementary, anti-interferon activities of bacteria.
TOPIC 3. IMMUNITY REACTIONS (1 LESSON)
One form of immunological reactivity is the body's ability to produce antibodies in response to an antigen. An antigen is a substance of a certain chemical structure that carries foreign genetic information. Antigens are complete, that is, they can cause the synthesis of antibodies and bind to them, and defective or haptens. Haptens are only able to bind to the antibody, but not to cause its synthesis in the body. Bacteria and viruses are represented by a complex system of antigens (tables 4, 5), some of them have toxic and immunosuppressive properties.
Table 4
Bacterial antigens
Table 5
Virus antigens
Immunological research methods - diagnostic methods studies based on the specific interaction of antigens and antibodies. Widely used for laboratory diagnostics infectious diseases, determination of blood groups, tissue and tumor antigens, protein species, recognition of allergies and autoimmune diseases, pregnancy, hormonal disorders as well as in research work. They include serological reactions, which usually include in vitro reactions of direct exposure to antigens and serum antibodies. Depending on the mechanism, serological reactions can be subdivided into reactions based on the phenomenon of agglutination; reactions based on the phenomenon of precipitation; lysis reactions and neutralization reactions.
Reactions based on the phenomenon of agglutination. Agglutination is the adhesion of cells or individual particles - carriers of an antigen with the help of an immune serum to this antigen. Agglutination reaction of bacteria using the appropriate antibacterial serum is one of the simplest serological reactions... A suspension of bacteria is added to various dilutions of the test blood serum and after a certain contact time at t ° 37 ° register at which highest dilution of blood serum agglutination occurs. Allocate fine-grained and coarse-cotton agglutination reactions. When bacteria bind through the H-antigen, a precipitate is formed from large conjugates ag-at, in the form of flakes. Upon contact with O-ar, a fine-grained sediment appears. The agglutination reaction of bacteria is used to diagnose many infectious diseases: brucellosis, tularemia, typhoid and paratyphoid fever, intestinal infections, and typhus.
Passive, or indirect, hemagglutination reaction(RPGA, RNGA). It uses erythrocytes or neutral synthetic materials (for example, latex particles), on the surface of which antigens (bacterial, viral, tissue) or antibodies are sorbed. Their agglutination occurs when the appropriate sera or antigens are added. Erythrocytes sensitized with antigens are called antigenic erythrocyte diagnosticum and are used to detect and titrate antibodies. Antibody sensitized erythrocytes. are called immunoglobulin erythrocyte diagnosticums and are used to detect antigens. The passive hemagglutination reaction is used to diagnose diseases caused by bacteria (typhoid and paratyphoid fever, dysentery, brucellosis, plague, cholera, etc.), protozoa (malaria) and viruses (influenza, adenovirus infections, viral hepatitis B, measles, tick-borne encephalitis, Crimean hemorrhagic fever, etc.).
Reactions based on the phenomenon of precipitation. Precipitation occurs as a result of the interaction of antibodies with soluble antigens. The simplest example of a precipitation reaction is the formation in a test tube of an opaque precipitation band at the border of antigen-antibody deposition. Various types of precipitation reactions in semi-liquid agar or agarose gels are widely used (method of double immunodiffusion according to Ouchterloni, method of radial immunodiffusion, immunoelectrophoresis), which are both qualitative and quantitative. As a result of free diffusion in the gel of antigens and antibodies in the zone of their optimal ratio, specific complexes are formed - precipitation bands, which are detected visually or by staining. A feature of the method is that each pair antigen-antibody forms an individual precipitation band, and the reaction does not depend on the presence of other antigens and antibodies in the system under study.
1.Put an approximate agglutination reaction on the glass. To do this, a drop of diagnostic serum is applied on a glass slide with a pipette and a drop of saline is placed next to it. A small amount of bacterial culture is introduced into each sample using a bacteriological loop and emulsified. After 2-4 minutes, in a positive case, flakes appear in the sample with serum, in addition, the drop becomes transparent. In the control sample, the drop remains uniformly cloudy.
2.Put a detailed agglutination reaction. To set up the reaction, take 6 tubes. The first 4 tubes are experimental, 5 and 6 are control. In all test tubes except 1 add 0.5 ml of saline solution. In the first 4 tubes, titrate the test serum (1:50; 1: 100; 1: 200; 1: 400). Add 0.5 ml of antigen to all tubes, except for the 5th tube. Shake the tubes and place in a thermostat (37 0 С) for 2 hours, then leave the samples at room temperature for 18 hours. The results are recorded according to the following scheme:
Complete agglutination, well-defined flocculent sediment, clear supernatant
Incomplete agglutination, pronounced sediment, slightly turbid supernatant
Partial agglutination, there is a slight sediment, the liquid is cloudy
Partial agglutination, the sediment is poorly expressed, the liquid is turbid
No agglutination, no sediment, turbid liquid.
3. To get acquainted with the formulation of the precipitation reaction in the diagnosis of the toxigenic strain of C.diphtheriae.
4. To disassemble the schemes of direct and indirect Coombs reactions.
Control questions
1. Immunity, its types
2. Central and peripheral organs of immunity. Functions, structure.
3. The main cells involved in immune responses.
4. Classification of antigens, properties of antigens, properties of haptens.
5. Antigenic structure of a bacterial cell, virus.
6. Humoral immunity: features, the main cells involved in humoral immunity.
7. B-lymphocytes, cell structure, maturation and differentiation phases.
8. T-lymphocytes: cell structure, maturation and differentiation phases.
9. Three-cell cooperation in the immune response.
10. Classification of immunoglobulins.
11. The structure of the immunoglobulin.
12. Incomplete antibodies, structure, meaning.
13. Immunity reactions, classification.
14. Agglutination reaction, setting options, diagnostic value.
15. Coombs' reaction, setting scheme, diagnostic value.
16. Reaction of precipitation, options for setting, diagnostic value.
Factors of nonspecific resistance (protection), which provide a non-selective nature of the response to an antigen and are the most stable form of immunity, are due to the innate biological characteristics of the species. They react to a foreign agent in a stereotyped manner and regardless of its nature. The main mechanisms of nonspecific defense are formed under the control of the genome during the development of the organism and are associated with natural physiological reactions wide range- mechanical, chemical and biological.
Among the factors of nonspecific resistance are:
unresponsiveness of macroorganism cells to pathogenic microorganisms and toxins, due to the genotype and associated with the absence on the surface of such cells of receptors for the adhesion of the pathogenic agent;
barrier function of the skin and mucous membranes, which is provided by the rejection of skin epithelial cells and active movements of the cilia of the ciliated epithelium of the mucous membranes. In addition, it is due to the release of exosecrets of sweat and sebaceous glands skin, specific inhibitors, lysozyme, acidic environment of gastric contents and other agents. Biological factors of protection at this level are due to the destructive effect of the normal microflora of the skin and mucous membranes on pathogenic microorganisms;
temperature reaction, at which the reproduction of most pathogenic bacteria stops. For example, the resistance of chickens to the causative agent of anthrax (B. anthracis) is due to the fact that their body temperature is within 41-42 ° C, at which bacteria are not capable of self-reproduction;
cellular and humoral factors of the body.
In the case of the penetration of pathogens into the body, humoral factors are included, which include proteins of the complement system, properdin, lysines, fibronectin, the cytokine system (interleukins, interferons, etc.). Develop vascular reactions in the form of a rapid local edema in the focus of damage, which retains microorganisms and does not allow them to enter the internal environment. Acute phase proteins appear in the blood - C-reactive protein and mannan-binding lectin, which have the ability to interact with bacteria and other pathogens. In this case, their capture and absorption by phagocytic cells are enhanced, i.e., opsonization of pathogens occurs, and these humoral factors play the role of opsonins.
Cellular factors of nonspecific protection include mast cells, leukocytes, macrophages, natural (natural) killer cells (NK cells, from the English "natural killer").
Mast cells are large tissue cells that contain cytoplasmic granules containing heparin and biologically active substances such as histamine, serotonin. During degranulation, mast cells secrete special substances that mediate inflammatory processes (leukotrienes and a number of cytokines). Mediators increase the permeability of the vascular walls, which allows complement and cells to exit into the tissues of the lesion. All this inhibits the penetration of pathogens into the internal environment of the body. NK cells are large lymphocytes that do not have T- or B-cell markers and are capable of spontaneously, without prior contact, killing tumor and virus-infected cells. In peripheral blood, they account for up to 10% of all mononuclear cells. NK cells are localized mainly in the liver, red pulp of the spleen, and mucous membranes.
Phagocytosis- a biological phenomenon based on the recognition, capture, absorption and processing of foreign substances by a eukaryotic cell. The objects for phagocytosis are microorganisms, the body's own dying cells, synthetic particles, etc. Phagocytes are polymorphonuclear leukocytes (neutrophils, eosinophils, basophils), monocytes and fixed macrophages - alveolar, peritoneal, Kupffer cells, dendritic cells of the spleen Langerhans and others.
In the process of phagocytosis (from the Greek phago - I devour, cytos - cells) there are several stages (Fig.15.1):
Approach of a phagocyte to a foreign corpuscular object (cell);
Adsorption of an object on the surface of a phagocyte;
Absorption of the object;
Destruction of the phagocytosed object.
The first phase of phagocytosis is carried out by positive chemotaxis.
Adsorption occurs by binding a foreign object to phagocyte receptors.
The third phase is carried out as follows.
The phagocyte envelops the adsorbed object with its outer membrane and draws (invaginates) it into the cell. Here a phagosome is formed, which then fuses with the lysosomes of the phagocyte. A phagolysosome is formed. Lysosomes are specific granules containing bactericidal enzymes (lysozyme, acid hydrolases, etc.).
Special enzymes are involved in the formation of active free radicals O 2 and H 2 O 2.
At the final stage of phagocytosis, the absorbed objects are lysis to low molecular weight compounds.
Such phagocytosis proceeds without the participation of specific humoral protective factors and is called pre-immune (primary) phagocytosis. It is this variant of phagocytosis that was first described by I.I.Mechnikov (1883) as a factor of nonspecific defense of the organism.
The result of phagocytosis is either the death of foreign cells (complete phagocytosis), or the survival and proliferation of captured cells (incomplete phagocytosis). Incomplete phagocytosis is one of the mechanisms of long-term persistence (experience) of pathogenic agents in a macroorganism and chronicity of infectious processes. Such phagocytosis often occurs in neutrophils and ends with their death. Incomplete phagocytosis was detected in tuberculosis, brucellosis, gonorrhea, yersiniosis and other infectious processes.
An increase in the speed and efficiency of the phagocytic reaction is possible with the participation of nonspecific and specific humoral proteins, which are called opsonins. These include proteins of the complement system C3b and C4b, acute phase proteins, IgG, IgM, etc. Opsonins have a chemical affinity for some components of the cell wall of microorganisms, bind to them, and then such complexes are easily phagocytosed because phagocytes have special receptors for molecules opsonins. The cooperation of various opsonins of blood serum and phagocytes constitutes the opsonophagocytic system of the body. Evaluation of the opsonic activity of blood serum is carried out by determining the opsonic index or opsonophagocytic index, which characterize the effect of opsonins on the absorption or lysis of microorganisms by phagocytes. Phagocytosis, in which specific (IgG, IgM) opsonin proteins are involved, is called immune.
Complement system(lat. complementum - supplement, means of replenishment) is a group of blood serum proteins that take part in nonspecific defense reactions: cell lysis, chemotaxis, phagocytosis, activation of mast cells, etc. Complement proteins belong to globulins or glycoproteins. They are produced by macrophages, leukocytes, hepatocytes and make up 5-10% of all blood proteins.
The complement system is represented by 20-26 proteins of blood serum, which circulate in the form of separate fractions (complexes), differ in physical and chemical properties and are denoted by the symbols C1, C2, C3 ... C9, etc. The properties and functions of the main 9 components of complement are well studied ...
In the blood, all components circulate in an inactive form, in the form of coenzymes. The activation of complement proteins (i.e., the assembly of fractions into a single whole) is carried out by specific immune and non-specific factors in the process of multistage transformations. Moreover, each component of the complement catalyzes the activity of the next. This ensures the sequence, the cascade of the entry of the complement components into the reaction.
The proteins of the complement system are involved in the activation of leukocytes, the development of inflammatory processes, the lysis of target cells and, by attaching to the surface of the cell membranes of bacteria, are able to opsonize (“dress”) them, stimulating phagocytosis.
There are 3 known ways to activate the complement system: alternative, classical and lectin.
Most an important component complement is C3, which is cleaved by the convertase, formed by any pathway of activation, into fragments C3a and C3b. The СЗb fragment participates in the formation of С5-convertase. This is the initial stage in the formation of the membranolytic complex.
In an alternative pathway, complement can be activated by polysaccharides, bacterial lipipolysaccharides, viruses and other antigens without the participation of antibodies. The initiator of the process is the СЗb component, which binds to the surface molecules of microorganisms. Further, with the participation of a number of enzymes and the protein properdin, this complex activates the C5 component, which attaches to the target cell membrane. Then a membrane-attacking complex (MAC) of C6-C9 components is formed on it. The process ends with membrane perforation and lysis of microbial cells. It is this way of starting a cascade of complementary proteins that takes place in the early stages of the infectious process, when specific immunity factors (antibodies) have not yet been developed. In addition, the C3b component, by binding to the bacterial surface, can act as an opsonin, enhancing phagocytosis.
The classic pathway of complement activation is triggered and proceeded with the participation of an antigen-antibody complex. IgM molecules and some IgG fractions in the antigen-antibody complex have special places, which are able to bind the C1 component of the complement. The C1 molecule consists of 8 subunits, one of which is an active protease. It participates in the cleavage of the C2 and C4 components with the formation of the C3-convertase of the classical pathway, which activates the C5 component and ensures the formation of the membrane-attacking complex C6-C9, as in the alternative pathway.
The lectin pathway of complement activation is due to the presence in the blood of a special calcium-dependent sugar-binding protein - mannan-binding lectin (MSL). This protein is able to bind mannose residues on the surface of microbial cells, which leads to the activation of a protease that cleaves components C2 and C4. This triggers the formation of a membrane-lysing complex, as in the classical complement activation pathway. Some researchers consider this path as a variant of the classical path.
In the process of cleavage of the C5 and C3 components, small fragments C5a and C3a are formed, which serve as mediators of the inflammatory reaction and initiate the development of anaphylactic reactions with the participation of mast cells, neutrophils and monocytes. These components are called complement anaphylatoxins.
The activity of complement and the concentration of its individual components in the human body can increase or decrease in various pathological conditions. There may be hereditary deficiencies. The complement content in animal sera depends on the species, age, season and even time of day.
The highest and most stable level of complement was observed in guinea pigs; therefore, native or lyophilized blood serum of these animals is used as a source of complement. The complement system proteins are very labile. They are rapidly destroyed when stored at room temperature, exposed to light, ultraviolet rays, proteases, solutions of acids or alkalis, removing Ca ++ and Mg ++ ions. Heating the serum at 56 ° C for 30 minutes leads to the destruction of complement, and this serum is called inactivated.
The quantitative content of complement components in peripheral blood is determined as one of the indicators of the activity of humoral immunity. In healthy individuals, the content of the C1 component is 180 μg / ml, C2 - 20 μg / ml, C4 - 600 μg / ml, C3 - 13 001 μg / ml.
Inflammation, as the most important manifestation of immunity, develops in response to tissue damage (primarily integumentary) and is aimed at localizing and destroying microorganisms that have entered the body. The inflammatory response is based on a complex of humoral and cellular factors of nonspecific resistance. Clinically, inflammation is manifested by redness, swelling, pain, localized fever, and dysfunction damaged organ or fabric.
The central role in the development of inflammation is played by vascular reactions and cells of the mononuclear phagocyte system: neutrophils, basophils, eosinophils, monocytes, macrophages and mast cells. When cells and tissues are damaged, in addition, various mediators are released: histamine, serotonin, prostaglandins and leukotrienes, kinins, acute phase proteins, including C-reactive protein, etc., which play an important role in the development of inflammatory reactions.
Bacteria that have entered the body after damage and their waste products activate the blood coagulation system, the complement system and the cells of the macrophage-mononuclear system. The formation of blood clots occurs, which prevents the spread of pathogens with blood and lymph and prevents the generalization of the process. When the complement system is activated, a membrane-attacking complex (MAC) is formed, which lyses microorganisms or opsonizes them. The latter enhances the ability of phagocytic cells to absorb and digest microorganisms.
The nature and outcome of the inflammatory process depend on many factors: the nature and intensity of the action of a foreign agent, the form of the inflammatory process (alternative, exudative, proliferative), its localization, the state of the immune system, etc. If the inflammation does not end within a few days, it becomes chronic and then it develops immune inflammation involving macrophages and T-lymphocytes.
Sustainable preservation of high productivity of farm animals largely depends on the skillful use of the adaptive and protective properties of their body by humans. It becomes necessary to systematically and comprehensively study the natural resistance of animals. In the conditions of farms, only those animals can produce the expected effect that have a high natural resistance to adverse environmental conditions.
The technology of production of products in animal husbandry must be combined with the physiological needs and capabilities of the animal.
It is known that in highly productive animals and poultry, the orientation of biochemical processes towards the synthesis of substances that make up products is very intense. This intensity of metabolic processes in animals is further aggravated by the coincidence of the productive period, to a large extent, with the period of gestation. From an immunobiological standpoint, the state of living organisms in modern conditions is characterized by a decrease in immunological reactivity and nonspecific immunity.
The problem of studying the natural resistance of animals was given the attention of many researchers: A.D. Ado; S.I. Plyaschenko; OK. Brown, D.I. Barsukova; I.F. Khrabustovsky.
The protective function of the blood professor A.Ya. Yaroshev characterized as follows: "The blood is a place where various kinds of antibodies are located, both formed in response to the intake of microorganisms, substances, toxins, and species that provide acquired and innate immunity."
Natural resistance and immunity are protective devices. The question of the advantage of one of these protective devices are debatable. It is undeniable that in incubation period before the development of immunity, the body has a decisive resistance to the infectious agent and often comes out the winner. It is this initial resistance to the infectious agent that is carried out by the factors of nonspecific protection. At the same time, a feature of natural resistance, in contrast to immunity, is the body's ability to inherit nonspecific defense factors.
Natural, or physiological resistance of an organism is a general biological property of both plants and animals. The body's resistance to harmful factors depends on its level. external environment, including to microorganisms.
In the field of studying natural immunity, the development of theoretical provisions and the application of the obtained achievements in the practice of agricultural production have done a lot of domestic and foreign breeders - plant breeders. As for animal husbandry, research on this most difficult and very important problem is rather scattered, separate, not united by a common direction.
It cannot be denied that artificial immunization of farm animals has played and continues to play an invaluable role in the fight against many infectious diseases, which inflicted huge damage on livestock, but one should not think that only in this way it is possible to preserve the welfare of animals for an infinitely long time.
More than a thousand infectious diseases caused by microorganisms are known to medicine and veterinary medicine. Even if vaccines and sera were developed against all these diseases, it is difficult to imagine their widespread practical application on a mass scale.
As you know, in animal husbandry, immunization is carried out only against the most dangerous infections in threatening areas.
At the same time, a gradual, undoubtedly, very long selection and selection of animals with high resistance will lead to the creation of individuals, if not completely, then in a significant part, resistant to most harmful factors.
The experience of domestic and foreign animal husbandry shows that it is not acutely infectious diseases that are more widespread on farms and poultry farms, but such infectious and non-infectious diseases that can occur against the background of a decrease in the level of natural resistance of the herd.
An important reserve for increasing the production of products and improving their quality is the reduction of morbidity and waste. This is possible with an increase in the general resistance of the organism by selecting individuals that are immune to various diseases.
The problem of increasing natural resistance is closely related to the use of genetic scientific interest and is of great economic importance. Immunization of animals and their genetic resistance must complement each other.
Breeding for resistance to some diseases individually can be effective, but selection for resistance to several diseases at once in parallel with selection based on productivity is practically impossible. Based on this, selection is necessary to increase the overall level of the body's natural resistance. There are many examples when one-sided selection for productivity without taking into account natural resistance led to premature culling and loss of valuable lines and families.
Create animals and birds with high level natural resistance requires special breeding and genetic programs, in which great attention should be paid to such issues as the establishment of the phenotype and genotype of a bird characterized by increased natural resistance, the study of the heritability of the trait of resistance, the establishment of a connection between the traits of natural resistance and economic useful features, the use of signs of natural resistance in selection. At the same time, the level of natural resistance should first of all reflect the body's ability to withstand unfavorable environmental factors and indicate the reserve of the body's defenses.
Control over the level of natural resistance can be planned for the periods of growth and productivity, taking into account the technology adopted in the farm, or forced before carrying out technological methods: the introduction of new equipment, the transfer of animals and poultry from one conditions of keeping to others, vaccination, limited feeding, the use of new feed additives and so on. This will allow you to timely identify negative sides measures taken and to prevent a decrease in productivity, to reduce the percentage of culling and mortality.
All data on the determination of the natural resistance of animals and poultry should be compared with other indicators for the control of growth and development, which are obtained in the zoological laboratory.
Control over the level of natural resistance should help in determining the planned figures for the safety of the livestock and in a timely manner to outline measures for existing violations.
Studies of the level of natural resistance make it possible, during the selection period, to select highly productive individuals that simultaneously have high resistance at normal functions physiological systems.
Routine studies of the level of natural resistance must be carried out on the same group at certain calendar times associated with the tension of metabolic processes at certain periods of productivity (different periods of productivity, periods of growth).
Natural resistance is a response of the whole organism, which is regulated by the central nervous system. Therefore, to judge the degree of natural resistance, one should use criteria and tests that reflect the state of reactivity of the organism as a whole.
The specificity of the functions of the immune system is determined by the processes induced by foreign substances, antigens, and based on the recognition of the latter. However, the basis for the deployment of specific immune processes is the more ancient reactions associated with inflammation. Since they pre-exist in any organism prior to the onset of any aggression and do not require the deployment of an immune response for their development, these defense mechanisms called natural, or congenital. They provide the first line of defense against biological attack. The second line of defense is the reaction of adaptive immunity - the antigen-specific immune response. The factors of natural immunity by themselves have a fairly high efficiency in preventing biological aggression and combating it, but in higher animals, these mechanisms, as a rule, are enriched with specific components that are, as it were, layered on them. The system of natural factors of immunity is borderline between the actual immune system and a field within the purview of pathophysiology, which also considers the mechanisms and biological significance of a number of manifestations of natural immunity that serve as constituents of the inflammatory response.
That is, along with immunological reactivity in the body, there is a system of nonspecific defense, or nonspecific resistance. Despite the fact that the nonspecific resistance of animals and poultry to various adverse environmental influences is provided to a greater extent by the leukocyte system of the body, however, it depends not so much on the number of leukocytes as on their nonspecific defense factors that are present in the body from the first day of life and remain until death. It includes the following components: impermeability of the skin and mucous membranes; acidity of stomach contents; the presence of bactericidal substances in blood serum and body fluids - lysozyme, properdin (a complex of whey protein, M + ions and complement), as well as enzymes and antiviral substances (interferon, heat-resistant inhibitors).
Factors of nonspecific protection are the first to be included in the fight when foreign antigens enter the body. They, as it were, prepare the ground for the further deployment of immune responses that determine the outcome of the struggle.
The natural resistance of animals to various adverse environmental influences is provided by nonspecific protective factors that are present in the body from the first day of life and persist until death. Among them, phagocytosis with its protective cellular mechanisms and humoral resistance factors, the most important of which are lysozyme, bactericidal factors. That is, phagocytes (macrophages and polymorphonuclear leukocytes) and a system of blood proteins called complement occupy a special position among the protection factors. They can be attributed to both nonspecific and immunoreactive protection factors.
Changes in the factors of nonspecific immunity in animals and poultry have age-related characteristics, in particular, with age, humoral ones increase and cellular ones decrease.
Humoral factors of nonspecific resistance just provide bactericidal and bacteriostatic effects of tissues and body juices and cause lysis of some types of microorganisms. The degree of manifestation of the protective properties of a living organism to a microbial agent is well illustrated by the total bactericidal activity of blood serum. The bactericidal activity of blood serum is an integral indicator of the antimicrobial activity of all antimicrobial substances present, both thermolabile (complement, properdin, normal antibodies) and thermostable (lysozyme, beta-lysine) principles.
Among the factors of the body's natural immunity is lysozyme - a universal, ancient protective enzyme, widespread in the plant and animal world. Lysozyme is especially widespread in the body of animals and humans: in blood serum, secretions of the digestive glands and respiratory tract, milk, lacrimal fluid, cervix, liver, spleen, and bird eggs.
Lysozyme is a basic protein with a molecular weight of 14-15 thousand D. Its molecule is represented by one polypeptide chain, consisting of 129 amino acid residues and having 4 disulfide bonds. Lysozyme in animals is synthesized and secreted by granulocytes, monocytes and macrophages.
Serum lysozyme plays at least a dual role. First, it has an antimicrobial effect on a wide range of saprophytic microbes, destroying mucoprotein substances in the cell walls. Secondly, its participation in the reactions of acquired immunity is not excluded. Beta-lysine has the property of destroying bacterial cells with a complement activator.
This enzyme has the basic properties of a protein, it causes a rapid lysis of living cells of some types of bacteria. Its action is expressed in the dissolution of specific mucopolysaccharide shells of microorganisms sensitive to it or in arresting their growth. In addition, lysozyme kills bacteria belonging to many other species, but does not cause them to lysis.
Lysozyme is contained in granulocytes and in active form is released as a result of even minimal cell damage into the liquid medium surrounding leukocytes. In this regard, it is no coincidence that this enzyme is ranked among the substances that determine the natural and acquired immunity of the body to infection.
The complement system is a complex complex of proteins, presented mainly in the β-globulin fraction, numbering, including regulatory, about 20 components, which account for 10% of blood serum proteins and representing a system of cascade-acting peptide hydrolases. The catabolism of the complement components is the highest in comparison with other proteins of the blood serum, with the renewal of up to 50% of the proteins of the system during the day.
Considering what a complex set are serum proteins in the complement system, it is not surprising that it took about 70 years to establish the fact that complement consists of 9 components, and they, in turn, can be subdivided into 11 independent proteins.
Complement was first described by Buchner in 1889 under the name "alexin" - a thermolabile factor, in the presence of which lysis of microbes is observed. Complement got its name due to the fact that it complements (complements) and enhances the action of antibodies and phagocytes, protecting the human and animal body from the majority bacterial infections... In 1896 Borde was the first to define complement as a factor present in fresh serum that is necessary for the lysis of bacteria and red blood cells. This factor did not change after preliminary immunization of the animal, which made it possible to clearly differentiate complement from antibodies. Since it was quickly realized that complement was not the only functional substance in serum, all attention was directed to its ability to stimulate the lysis of intact cells; complement has come to be considered almost exclusively in light of its ability to act on cell lysis.
The study of complement in the aspect of kinetic analysis of the stages leading to cell lysis provided accurate data on the sequential interaction of complement components and important evidence of the multicomponent complement system. The identification of these factors has shown that complement is an important mediator in the inflammatory process.
Complement is the most important activator of the entire system of acquired and normal antibodies, which, in its absence, are ineffective in immune reactions (hemolysis, bacteriolysis, partly the agglutination reaction). Complement is a system of cascade-acting peptide hydrolases designated from C1 to C9. Determined that most of the component is synthesized by hepatocytes and other liver cells (about 90%, C3, C6, C8, factor B, etc.), as well as monocytes - macrophages (C1, C2, C3, C4, C5).
Various components of complement and their fragments formed during the activation process are capable of causing inflammatory processes, cell lysis, stimulate phagocytosis. The end result may be the assembly of a complex of C5-, C6-, C7-, C8-, and C9- components, attacking the membrane with the formation of channels in it and increasing the permeability of the membrane to water and ions, which causes cell death.
Complement activation can occur in two main ways: alternative - without the participation of antibodies and classical - with the participation of antibodies.
Bactericidal factors are closely related, and the deprivation of serum of one of them causes changes in the content of others.
So, complement together with antibodies or other sensitizing agents can kill some bacteria (for example, Vibrio, Salmonella, Shigella, Esherichia) by damaging the cell wall. Muschel and Treffers showed that the bactericidal response in the S. Typhi - C ' guinea pig- rabbit or human antibodies "resembles in some respects a hemolytic reaction system: MD ++ enhances bactericidal activity; bactericidal curves are similar to hemolytic response curves; there is an inverse relationship between the bactericidal activity of antibodies and complement; very few antibodies are needed to kill one bacterial cell.
In order for damage or change to the cell wall of bacteria to occur, lysozyme is needed, and this enzyme acts on bacteria only after processing them with antibodies and complement. Normal serum contains enough lysozyme to damage bacteria, but if the lysozyme is removed, no damage is observed. Adding crystalline lysozyme egg white restores bacteriolytic activity of the antibody-complement system.
In addition, lysozyme accelerates and enhances the bactericidal effect. These observations can be explained on the basis of the assumption that the antibody and complement, in contact with the bacterial cell membrane, expose the substrate that lysozyme acts on.
In response to the entry of pathogenic microbes into the bloodstream, the number of leukocytes increases, which is called leukocytosis. The main function of leukocytes is to destroy pathogenic microbes. Neutrophils, which make up the majority of leukocytes, possessing amoeboid movements, are able to move. Coming into contact with microbes, these large cells capture them, sucking them into the protoplasm, digest and destroy them. Neutrophils capture not only living, but also dead bacteria, the remnants of destroyed tissues and foreign bodies... Lymphocytes, in addition, are involved in recovery processes after tissue inflammation. One white blood cell can kill more than 15 bacteria and sometimes dies in the process. That is, the need to determine the phagocytic activity of leukocytes as an indicator of the body's resistance is obvious and does not require justification.
Phagocytosis is a special form of endocytosis in which large particles are absorbed. Phagocytosis is carried out only by specific cells (neutrophils and macrophages). Phagocytosis is one of the earliest human defense mechanisms and different types animals from many external influences... In contrast to the study of other effective functions of neutrophils, the study of phagocytosis has already become traditional. As you know, phagocytosis is a multifactorial and multistage process, and each of its stages is characterized by the development of a cascade of complex biochemical processes.
The process of phagocytosis is divided into 4 stages: approaching the phagocytosed object, contact and adhesion of particles to the surface of the leukocyte, absorption of particles and their digestion.
First stage: The ability of leukocytes to migrate towards the phagocytosed object depends both on the chemotactic properties of the object itself and on the chemotactic properties of blood plasma. Chemotaxis is movement in a given direction. Therefore, it is chemotaxis that is a definite guarantee of the inclusion of neutrophils in the maintenance of immune homeostasis. Chemotaxis includes at least two phases:
1. Orientation phase, during which cells either stretch out or form pseudopodia. About 90% of the cells are oriented in a given direction within a few seconds.
2. The phase of polarization, during which the interaction between the ligand and the receptor takes place. Moreover, the uniformity of the response to chemotactic factors of different nature gives reason to assume the universality of these abilities, which, apparently, underlie the interaction of the neutrophil with the external environment.
The second stage: adhesion of particles to the surface of the leukocyte. The leukocyte responds to adhesion and capture of particles by increasing the level of metabolic activity. There is a threefold increase in the absorption of O2 and glucose, the intensity of aerobic and anaerobic glycolysis increases. This state of metabolism during phagocytosis is called "metabolic explosion". It is accompanied by degranulation of neutrophils. The content of the granules is released into the extracellular environment by exocinosis. However, the degranulation of neutrophils during phagocytosis is a completely ordered process: first specific granules merge with the outer cell membrane, and only then azurophilic ones. So, phagocytosis begins with exocytosis - an emergency release into the external environment of bactericidal proteins and acid hydrolases involved in the resorption of immune complexes and the neutralization of extracellular bacteria.
The third stage: after the contact and adhesion of particles to the surface of the phagocyte, their absorption follows. The phagocytosed particle enters the cytoplasm of the neutrophil as a result of invagination of the outer cell membrane. The invaginated part of the membrane with the enclosed particle is split off, as a result of which a vacuole or phagosome is formed. This process can occur simultaneously in several areas of the cell surface of the leukocyte. Contact lysis and fusion of the membranes of the lysosomal granules and the phagocytic vacuole lead to the formation of a phagolysosome and the entry of bactericidal proteins and enzymes into the vacuole.
Fourth stage: intracellular cleavage (digestion). The phagocytic vacuoles formed during the protrusion and lacing of the cell membrane merge with the granules in the cytoplasm. As a result of this, digestive vacuoles appear, filled with the contents of the granules and phagocytosed particles. In the first three minutes after phagocytosis, a neutral pH is maintained in vacuoles filled with bacteria, which is optimal for the action of enzymes, specific granules - lysozyme, lactoferin and alkaline fasphatase. Then the pH value drops to 4, as a result of which an optimum is created for the action of the enzymes of azurophilic granules - myeloperoxidase and water-soluble acid hydrolases.
The destruction of living objects, or complete phagocytosis, should be considered as the final phenomenon, in which many links of the cell's effector potential are focused. A fundamental stage in the study of the antimicrobial properties of phagocytes was the development of ideas that the killing of bacteria (killer effect) has nothing to do with the degradation (digestion) of dead objects - killed microbes, debris of their own tissues, cells, etc. This is facilitated by the discovery of new bactericidal factors and systems, mechanisms of their cytotoxicity and methods of connection to phagocytic reactions. In terms of reactivity, all bactericidal factors of neutrophils can be divided into 2 groups.
The first includes components preformed in a mature neutrophil. Their level does not depend on the stimulation of the cell, but is entirely determined by the amount of substance synthesized in the process of granulopoiesis. These include lysozyme, some proteolytic enzymes, lactoferrin, cationic proteins and low molecular weight peptides called "defensins" (from English defince - protection). They lyse (lysozyme), kill (cationic proteins) or inhibit the growth of bacteria (lactoferrin). Their role in antimicrobial protection is confirmed by observations made in anaerobic mode: neutrophils, deprived of the opportunity to use the bactericidal properties of activated oxygen, normally killed microorganisms.
Factors of the second group are formed or sharply activated upon stimulation of a neutrophil. Their content is the higher, the more intense the reaction of the cells. An increase in oxidative metabolism leads to the formation of oxygen radicals, which, together with hydrogen peroxide, myeloperoxidase and halogens, constitute the effector link of the oxygen-dependent cytotoxicity apparatus. It would be wrong to oppose different antimicrobial factors to each other. Their effectiveness largely depends on mutual balance, the conditions in which phagocytosis occurs, the type of microbe. It is clear, for example, that in anaerobic environment in the foreground are biocidal moments, independent of oxygen. They kill many bacteria, but even one resistant virulent strain can reveal the failure of such a system. Antimicrobial potential consists of the sum of mutually complementary, often mutually compensating interactions, which ensure the maximum effectiveness of bactericidal reactions. Damage to its individual links weakens the neutrophil, but does not mean complete helplessness in defense against infectious agents.
Consequently, the transformation of our ideas about granulocytes, in particular about neutrophils, for last years has undergone extremely large changes, and today the heterogeneity of the functional capabilities of neutrophils hardly gives reason to class them among any known cells involved in different forms immunological response. This is confirmed by both the huge spectrum of functional capabilities of neutrophils and the sphere of their influence.
Changes in natural resistance depending on various factors are of great interest.
One of the most important aspects of the problem of the natural stability of the organism is the study of its age characteristics. Reactive properties in a growing organism develop gradually and are finally formed only at a certain level of general physiological maturation. Therefore, young and adult organisms have different susceptibility to diseases, react differently to the effects of pathogenic agents.
The postnatal period of development of most mammals is characterized by a state of decreased reactivity of the organism, expressed by the complete absence or weak manifestation of nonspecific humoral factors. This period is also characterized by an inadequate inflammatory response and a limited manifestation of specific humoral defense factors. As the development proceeds, the reactivity of the animal organism gradually becomes more complicated and improved, which is associated with the development of the endocrine glands, the formation of a certain level of metabolism, the improvement of protective devices against infections, intoxication, and so on.
Cellular defense factors in the body of animals appear earlier than humoral ones. Calves have a cage protective function organism, most pronounced in the first days after birth. At an older age, the degree of phagocytosis gradually increases with fluctuations in the opsonophagocytic index upward or downward, depending on the conditions of detention. The transition from dairy feed to plant feed reduces the phagocytic activity of leukocytes. Vaccination of calves in the first days of life increases the activity of phagocytosis.
At the same time, in calves born from non-immunized cows, the phagocytic activity of leukocytes is 5 times lower than in calves born from cows immunized with paratyphoid antigen. Feeding colostrum also increased the activity of leukocytes.
Phagocytic reactions in calves increase up to 5 days of age, then begin to decline sharply at the age of 10 days. Most low rates phagocytosis is noted at 20 days of age. Phagocytic activity of leukocytes during this period is even lower than in one-day-old calves. Starting from 30 days of age, there is a gradual increase in the phagocytic activity of leukocytes and the intensity of absorption of microorganisms by them. These indicators reach their maximum values at the age of 6 months. In the future, the indicators of phagocytosis change, but their values remain practically at the level of 6 months of age. Consequently, the cellular defense factors by this age in the body of the calves are already fully formed.
In newborn calves, normal agglutinins to the Gertner antigen are absent and appear only at 2 ... 2.5 months of age. Calves vaccinated with the paratyphoid vaccine in the first days of life do not develop antibodies. Agglutinins to this antigen appear only at 10 ... 12 days of age and are formed in a low titer up to 1.5 months. In the first 3 ... 7 days of calves' life, they are weakly expressed and reach the level of adult animals only by 2- months of age.
The lowest level of bactericidal activity in the blood serum of calves is observed in newborns before colostrum intake. On the 3rd day after birth, the bactericidal activity of blood serum increases, and by the age of 2 months it practically reaches the level of adult animals.
Lysozyme is not found in newborn calves prior to colostrum feeding. After drinking colostrum, lysozyme appears, but by the 10th day it almost halves. However, by the age of one month, the lysozyme titer gradually rises again. By this time, the calves are already capable of producing lysozyme on their own. At 2 months of age, the titer of lysozyme reaches its maximum value, then until 6 months of age its amount is maintained at approximately the same level, after which the titer decreases again at the age of 12 months.
As you can see, in the first 10 days of calves' life, the high ability of leukocytes to phagocytosis compensates for the lack of bactericidal activity of blood serum. In later periods, changes in the bactericidal activity of blood serum are wavy in nature, which, apparently, is associated with the conditions of detention and the seasons of the year.
On the first day of life, lambs have a relatively high phagocytic index, which sharply decreases by 15 days of age, then increases again and reaches its maximum by 2 months of age or somewhat later.
The age-related dynamics of the humoral factors of the natural resistance of the organism in lambs has also been studied in some detail. So, in the first days of life, they celebrate reduced rates natural resistance. The ability to produce antibodies in them appears at 14 ... 16 days of age and reaches the level of immunological reactivity of adult animals by 40 ... 60 days. In the first days of lambs' life, the inhibition of microbes upon contact with blood serum is weakly expressed, at 10 ... 15 days of age, the bactericidal activity of serum slightly increases and by 40 ... 60 days it reaches the level characteristic of adult sheep.
In piglets from birth to 6 months of age, a certain pattern of changes in the indicators of cellular and humoral protection factors is also noted.
In piglets, the lowest rates of phagocytosis are observed at 10 days of age, subsequently, up to 6 months of age, their gradual increase is observed. That is, by the age of 10 days in piglets there is a sharp drop in all indicators of phagocytosis. The most pronounced manifestation of phagocytosis is observed in piglets at 15 days of age. Early weaning and artificially fed piglets have lower phagocytic index values compared to piglets fed under the sow, although early weaning from the uterus did not affect their growth.
The smallest indices of opsono-phagocytic reaction are observed at the age of 20 days. During this period, not only the phagocytic activity of leukocytes decreases, but also their number in 1 mm3 of blood (phagocytic capacity) decreases. A sharp decrease in phagocytosis indicators is apparently associated with the cessation of the supply of antibodies with colostrum that promote phagocytosis. From 20 days of age, the phagocytic activity of leukocytes gradually increases and reaches a maximum at 4 months of age.
Complementary activity in piglets begins to be detected only at 5 days of age and, gradually increasing, by 2 ... 3 months of life reaches the level of adult animals.
Formation of a high titer of serum proteins in piglets occurs regardless of the vaccination of sows, by the end of the fourth week of life. The bactericidal properties of blood in piglets are most pronounced by the third week of life.
At 2 days of age, piglets have a well-expressed ability of blood serum to inhibit the growth of test microbes.
By 10 days of age, a sharp decline bactericidal ability of serum. At the same time, not only the intensity of suppression of the growth of microbes by serum decreases, but also the duration of its action. In the future, as the age of the animals increases, the bactericidal activity of blood serum increases.
Consequently, young animals of the first 3 ... 4 days of life are characterized by weak immunological maturity, their natural resistance to the adverse effects of environmental factors is low, which is associated with high morbidity and mortality during this period.
In birds, the early period of development (60 days) is characterized by a weak manifestation of humoral factors of nonspecific immunity of the body. In contrast to these indicators, the body of a bird at the early stage of ontogenesis contains a high amount of lysozyme. With regard to cellular protective factors, these indicators are quite high.
During the period of completion of juvenile molting and puberty of the organism, each specific indicator of the natural resistance of the organism has its own individual dynamics of change. Thus, the redox function of the blood continues to grow steadily. At 150 days of age, the complementary activity of blood serum in replacement calves significantly increases. The content of lysozyme in the blood serum has a clear tendency to decrease. The bactericidal activity of blood serum at this stage of postembryonic development of poultry significantly increases and exceeds the level of 60-day-old chickens. The period of puberty in birds was characterized by a slight decrease in the phagocytic intensity of pseudo-eosinophilic granulocytes and an increase in the percentage of phagocytic pseudo-eosinophilic granulocytes.
The third period of the study, in comparison with the first and second, is largely determined by the egg production of the bird. With the onset of oviposition and its subsequent increase, a more significant decrease in the redox function of the blood occurs. The complementary activity of blood serum increases with an increase in egg production and its maximum amount was recorded at 210-300 days of age, which corresponded to the peak of egg-laying. Bactericidal activity tends to increase by the beginning of oviposition to its peak, and then decreases. This, apparently, is associated with a more intense activity of the egg production organs. With an increase in the level of oviposition, the phagocytic intensity and the percentage of phagocytic pseudo-eosinophilic granulocytes in adult birds increase in comparison with pullets. Thus, we can say that the level of their productivity has a great influence on the indices of natural resistance in poultry; the higher the productivity, the more intense the nonspecific protective factors of the organism.
Humoral factors include: complement, interferons, lysozyme, beta-lysines and cellular factors: neutrophilic leukocytes (microphages).
The main humoral factor of nonspecific resistance is complement- a complex complex of serum proteins (about 20), which are involved in the destruction of foreign antigens, activation of coagulation, the formation of kinins. Complement is characterized by the formation of a fast, multiply amplified response to the primary signal due to a cascade process. Complement can be activated in two ways: classic and alternative. In the first case, activation occurs due to attachment to the immune complex (antigen-antibody), and in the second - due to attachment to the lipopolysaccharides of the cell wall of microorganisms, as well as endotoxin. Regardless of the activation pathways, a membrane attacking complex of complement proteins is formed, which destroys the antigen.
Second and not less important factor, is an interferon... It is alpha-leukocyte, beta-fibrous and gamma-interferonimmune. They are produced by leukocytes, fibroblasts and lymphocytes, respectively. The first two are produced constantly, and interferon gamma is produced only if the virus enters the body.
In addition to complement and interferons, humoral factors include lysozyme and beta-lysines... The essence of the action of these substances lies in the fact that, being enzymes, they specifically destroy lipopolysaccharide sequences in the composition of the cell wall of microorganisms. The difference between beta-lysines and lysozyme is that they are produced in stressful situations. In addition to these substances, this group includes: C-reactive protein, acute phase proteins, lactoferrin, properdin, etc.
Nonspecific cell resistance provided by phagocytes: macrophages - monocytes and microphages - neutrophils.
To ensure phagocytosis, these cells are endowed with three properties:
- Chemotaxis - directed movement towards the object of phagocytosis;
- Adhesiveness - the ability to fixate on the object of phagocytosis;
- Biocidal - the ability to digest an object of phagocytosis.
The latter property is provided by two mechanisms - oxygen-dependent and oxygen-independent. Oxygen dependent mechanism associated with the activation of membrane enzymes (NAD oxidase, etc.) and the production of biocidal free radicals that arise from glucose and oxygen on a special cytochrome B-245. Oxygen independent the mechanism is associated with proteins of lysosomes, which are laid in bone marrow... Only a combination of both mechanisms ensures complete digestion of the phagocytosis object.
Lysozyme - a thermostable protein, such as a mucolytic enzyme. Contained in tears, saliva, peritoneal fluid, blood plasma and serum, in leukocytes, breast milk, etc. Produced by monocytes and tissue macrophages, causes the lysis of many bacteria, is inactive against viruses.
Compliment system- a multicomponent self-assembled system of serum proteins, which plays an important role in maintaining homeostasis. It is activated in the process of self-assembly, i.e. sequential attachment to the resulting complex of individual fractions. They are produced in liver cells by mononuclear phagocytes and are contained in the blood serum in an inactive state.
Complement has a number of functions:
- cytolytic and cytotoxic action of the target cell;
- anaphylotoxins are involved in immunopathological reactions;
- the efficiency of phagocytosis of immune complexes (via Fc receptors);
- the C3b fragment promotes the binding and uptake of immune complexes by phagocytes;
- fragments C3b, C5a and Bb (chemoattractants) are involved in the development of inflammation.
Interferons- nonspecifically protect MCÒ cells from viral infection (different viruses). At the same time, it has a species specificity - human interferon, is active only in Ò of a person. It also has antiproliferative (antitumor), immunomodulatory effects.
Depending on their origin, according to their primary structure and functions, they are divided into 3 classes:
- Leukocyte α-interferon is obtained in donor blood leukocyte cultures, using viruses that are not dangerous to humans (vaccinia viruses, etc.) as interferonogens. It exhibits a pronounced antiviral and antiproliferative (antitumor) effect.
- Fibroblast β-interferon is obtained in semi-transplanted cultures of human diploid cells, mainly antitumor activity.
- Immune γ-interferon is obtained in transplanted cultures of lymphoblastoid cells under the influence of mitogens B! or P! origin. It has a less pronounced antiviral effect, but a strong immunomodulatory effect.
The mechanism of the antiviral action of interferon:
Interferon leaves the affected cell and binds to specific receptors (ganglioside-like substances) of the same or neighboring cells. Receptors signal for the synthesis of enzymes - protein kinase and endonuclease. Enzymes are activated by viral replicative complexes. In this case, endonuclease cleaves viral mRNA, and protein kinase blocks the translation of viral proteins Þ suppression of viral reproduction.
Interferon does not save an already affected cell, but protects neighboring cells from infection.
Resistance (from lat. resistere - resist, resist) - the body's resistance to the action of extreme stimuli, the ability to resist without significant changes in the constancy of the internal environment; this is the most important qualitative indicator of reactivity;
Nonspecific resistance is the resistance of the organism to damage (G. Selye, 1961), not to any particular damaging agent or group of agents, but in general to damage, to various factors, including extreme ones.
It can be congenital (primary) and acquired (secondary), passive and active.
Congenital (passive) resistance is due to the anatomical and physiological characteristics of the organism (for example, the resistance of insects, turtles, due to their dense chitinous cover).
Acquired passive resistance occurs, in particular, with serotherapy, replacement blood transfusion.
Active nonspecific resistance is due to protective and adaptive mechanisms, arises as a result of adaptation (adaptation to the environment), training to a damaging factor (for example, an increase in resistance to hypoxia due to acclimatization to a high mountain climate).
Biological barriers provide nonspecific resistance: external (skin, mucous membranes, respiratory organs, digestive apparatus, liver, etc.) and internal - histohematogenous (hematoencephalic, hematoophthalmic, hematolabyrinth, hemato-testicular). These barriers, as well as biologically active substances contained in fluids (complement, lysozyme, opsonins, properdin), perform protective and regulatory functions, maintain the composition of the nutrient medium that is optimal for the organ, and help maintain homeostasis.
FACTORS REDUCING NON-SPECIFIC RESISTANCE OF THE BODY. WAYS AND METHODS OF ITS INCREASING AND STRENGTHENING
Any impact that changes the functional state of regulatory systems (nervous, endocrine, immune) or executive (cardiovascular, digestive, etc.), leads to a change in the reactivity and resistance of the body.
Factors that reduce nonspecific resistance are known: mental trauma, negative emotions, functional inferiority of the endocrine system, physical and mental overwork, overtraining, starvation (especially protein), malnutrition, lack of vitamins, obesity, chronic alcoholism, drug addiction, hypothermia, colds, overheating, pain trauma, detraining of the body, its individual systems; hypodynamia, a sharp change in the weather, prolonged exposure to direct sunlight, ionizing radiation, intoxication, past diseases, etc.
There are two groups of pathways and methods that increase nonspecific resistance.
With a decrease in vital activity, loss of the ability to independently exist (tolerance)
2. Hypothermia
3. Ganglion blockers
4. Hibernation
While maintaining or increasing the level of vital activity (SNPS - a state of not specifically increased resistance)
1 1. Training of basic functional systems:
Physical training
Hardening to low temperatures
Hypoxic training (adaptation to hypoxia)
2 2. Changing the function of regulatory systems:
Autogenic training
Verbal suggestion
Reflexology (acupuncture, etc.)
3 3. Non-specific therapy:
Balneotherapy, balneotherapy
Autohemotherapy
Protein therapy
Nonspecific vaccination
Pharmacological agents (adaptogens - ginseng, eleutherococcus, etc.; phytocides, interferon)
To the first group include the impacts with the help of which resistance increases due to the loss of the body's ability to exist independently, a decrease in the activity of vital processes. These are anesthesia, hypothermia, hibernation.
When an animal is infected in hibernation with plague, tuberculosis, anthrax, diseases do not develop (they occur only after it awakens). In addition, resistance to radiation exposure, hypoxia, hypercapnia, infections, and poisoning increases.
Anesthesia contributes to an increase in resistance to oxygen starvation, electric current. In a state of anesthesia, streptococcal sepsis and inflammation do not develop.
With hypothermia, tetanus and dysentery intoxication is weakened, the sensitivity to all types of oxygen starvation, to ionizing radiation decreases; increased resistance to cell damage; allergic reactions are weakened, in the experiment, the growth of malignant tumors slows down.
In all these conditions, a deep inhibition of the nervous system and, as a consequence, of all vital functions occurs: the activity of the regulatory systems (nervous and endocrine) is inhibited, metabolic processes are reduced, chemical reactions are inhibited, the need for oxygen decreases, blood and lymph circulation slows down, the temperature decreases body, the body switches to a more ancient metabolic pathway - glycolysis. As a result of the suppression of the processes of normal vital activity, active defense mechanisms are also turned off (or inhibited), an areactive state arises, which ensures the body's survival even in very difficult conditions. At the same time, he does not resist, but only passively transfers the pathogenic action of the environment, almost not reacting to it. This state is called portability(increased passive resistance) and is a way of survival of the organism in adverse conditions, when it is impossible to actively defend oneself, it is impossible to avoid the action of an extreme stimulus.
To the second group include the following methods of increasing resistance while maintaining or increasing the level of vital activity of the body:
Adaptogens are agents that accelerate adaptation to adverse influences and normalize stress-induced disturbances. They have a broad therapeutic effect, increase resistance to a number of factors of physical, chemical, biological nature. The mechanism of their action is associated, in particular, with their stimulation of the synthesis of nucleic acids and protein, as well as with the stabilization of biological membranes.
Using adaptogens (and some other drugs) and adapting the body to the action of unfavorable environmental factors, it is possible to form a special state nonspecifically increased resistance - SNPS. It is characterized by an increase in the level of vital activity, mobilization of active defense mechanisms and functional reserves of the body, increased resistance to the action of many damaging agents. An important condition for the development of SNPS is a dosed increase in the force of exposure to unfavorable environmental factors, physical exertion, the exclusion of overloads, in order to avoid a breakdown of adaptation-compensatory mechanisms.
Thus, the more stable is the organism that is better, more actively resists (SNPS) or is less sensitive and has greater tolerance.
The management of the reactivity and resistance of the organism is a promising direction in modern preventive and curative medicine. Increasing nonspecific resistance is an effective way to strengthen the body in general.
Loading ...