Effect of ionizing radiation on the immune system. The effect of radiation on the immune system

Sources of ionizing radiation (radionuclides) can be outside the body and (or) inside it. If animals are exposed to radiation from the outside, then they talk about external exposure, and the effect of ionizing radiation on organs and tissues from incorporated radionuclides is called internal irradiation. In real conditions, various options for both external and internal irradiation are most often possible. Such options are called combined radiation injuries.

The dose of external exposure is formed mainly due to the impact of g-radiation; b- and c-radiation do not make a significant contribution to the total external exposure of animals, since they are mainly absorbed by the air or the epidermis of the skin. Radiation damage to the skin by β-particles is possible mainly when livestock is kept in open areas at the time of the fallout of radioactive products of a nuclear explosion or other radioactive fallout.

The nature of external exposure of animals over time can be different. Various options are possible single exposure when animals are exposed to radiation for a short period of time. In radiobiology, it is customary to consider a single exposure to radiation exposure for no more than 4 days. In all cases where animals are exposed to external irradiation intermittently (they may vary in duration), there is fractionated (intermittent) irradiation. With continuous long-term exposure to ionizing radiation on the body of animals, they speak of prolonged irradiation.

Allocate common (total) exposure in which the entire body is exposed to radiation. This type of exposure occurs, for example, when animals live in areas contaminated with radioactive substances. In addition, under the conditions of special radiobiological studies, local irradiation, when one or another part of the body is exposed to radiation! With the same dose of radiation, the most severe effects are observed with total exposure. For example, when irradiating the whole body of animals at a dose of 1500 R, almost 100% of their death is noted, while irradiation of a limited area of the body (head, limbs, thyroid gland, etc.) does not cause any serious consequences. In the following, the consequences of only general external exposure of animals are considered.

Effect of ionizing radiation on immunity

Small doses of radiation do not seem to have a noticeable effect on the immune system. When animals are irradiated with sublethal and lethal doses, a sharp decrease in the body's resistance to infection occurs, which is due to a number of factors, among which the most important role is played by: a sharp increase in the permeability of biological barriers (skin, respiratory tract, gastrointestinal tract, etc.), inhibition of the bactericidal properties of the skin , blood serum and tissues, a decrease in the concentration of lysozyme in saliva and blood, a sharp decrease in the number of leukocytes in the bloodstream, inhibition of the phagocytic system, adverse changes in the biological properties of microbes permanently residing in the body - an increase in their biochemical activity, an increase in pathogenic properties, an increase in resistance and etc.

Irradiation of animals in sublethal and lethal doses leads to the fact that from large microbial reservoirs (intestines, respiratory tract, skin) a huge amount of bacteria enters the blood and tissues.! At the same time, a period of sterility is conditionally distinguished (its duration is one day), during which microbes are practically not detected in tissues; the period of contamination of regional lymph nodes (usually coincides with the latent period); the bacteremic period (its duration is 4--7 days), which is characterized by the appearance of microbes in the blood and tissues, and, finally, the period of decompensation of protective mechanisms, during which there is a sharp increase in the number of microbes in organs, tissues and blood (this period occurs a few days before death).

Under the influence of large doses of radiation, causing partial or complete death of all irradiated animals, the body is unarmed both to endogenous (saprophytic) microflora and exogenous infections. It is believed that during the height of acute radiation sickness, both natural and artificial immunity are greatly weakened. However, there are data indicating a more favorable outcome of the course of acute radiation sickness in animals immunized before exposure to ionizing radiation. At the same time, it has been experimentally established that vaccination of irradiated animals aggravates the course of acute radiation sickness, and for this reason it is contraindicated until the disease resolves. On the contrary, a few weeks after irradiation in sublethal doses, the production of antibodies is gradually restored, and therefore, already 1-2 months after exposure to radiation, vaccination is quite acceptable.

The functioning of the human body to a certain extent is provided by relationships with environmental factors. Of particular importance is its effect on immune activity. These factors can be divided into 3 main groups.

Abiotic - temperature, humidity, daylight hours, barometric pressure, magnetic field disturbance, chemical composition of air, soil, water.

Biotic - microflora, flora and fauna.

Anthroponotic - physical (electromagnetic waves, ionizing radiation, noise, vibration, ultrasound, ultraviolet radiation); chemical (emissions from industrial enterprises and transport, contact with chemicals in production, in agriculture); biological (waste of factories for the production of biological products, food industry); socio-ecological (demographic shifts, urbanization, migration of the population, changes in the nature of nutrition, living conditions, psychophysical stress, medical measures).

As already mentioned, the immune system is highly sensitive to environmental changes. Therefore, studies of immune reactivity should be carried out at the stage when inducing factors have not yet led to the development of diseases, but have already caused immune damage. It is clear that the resistance of the immune system to negative influences on the body depends on the genotype, health status, and much more. Nevertheless, general patterns of response exist under these conditions as well.

The sensitivity of individual parts of the immune system to any factors is different, but in any case, it is a critical target for a large number of eubiotics and other influences. This circumstance causes the formation of prenosological changes in immune reactivity in the body, which, on the one hand, are markers of unfavorable living conditions, and on the other hand, provide the basis for the subsequent development of pathology, chronicity or aggravation of existing diseases.

11.1. IMMUNE REACTIVITY AND THE MICROBIAL ENVIRONMENT

The concept of "microbial environment" includes not only normal automicroflora, but also those microorganisms that a person encounters in everyday life, at work, and in a medical institution.

Certain changes in the composition of the microflora of the body occur under the influence of various factors. This is observed as a result of prolonged use of large doses of antibacterial drugs and in a number of other cases. The human microflora is composed of several compartments. The first - own, constant, capable of self-sustaining, includes a limited number of species. Second - this is a true microflora, limitedly capable of self-sustaining, it consists of a significantly larger number of species. It is inconsistent in composition. Third - passing, random microflora. Its representatives in the body die, and if they multiply, they are very limited, and are quickly eliminated.

Simplification of the microflora creates favorable conditions for the colonization of the macroorganism by new species or varieties, and these processes occur with the formation of secondary immune deficiency in patients.

In modern conditions, the number of so-called nosocomial, hospital infections is increasing - infectious processes caused by pathogens circulating in medical institutions. This pathology is 2-30%, with mortality from 3.5 to 60% of all infectious diseases. In surgical clinics, the frequency of nosocomial infections is 46.7 cases per 1000, in therapeutic clinics - 36.3, in gynecology - 28.1, in maternity wards - 15.3, in pediatrics - 13.9.

Hospital infections occur for a number of reasons.

Firstly, because patients develop secondary immune disorders, most often immune deficiency as a result of the underlying disease.

Secondly, many drugs (antibiotics, sulfonamides, etc.) cause a simplification of automicroflora.

Thirdly, in large hospitals, the risk of infection of patients with hospital strains of microorganisms increases. Indeed, on an area of more than 15-16 km 2 there are 3 million 300 thousand beds, on which 64 million patients and 6 million medical workers are accommodated during the year with a density of 200 thousand people / km 2.

The cause of nosocomial infections can be more than 2000 types of pathogenic, opportunistic microorganisms, sometimes multi-resistant to 4-5 antibacterial drugs simultaneously, circulating in hospitals for decades. These include staphylococci, pseudomonas, respiratory entero- and rotaviruses, hepatitis A viruses, anaerobic bacteria, molds and yeasts, legionella.

Fourth, invasive aggression, characteristic of modern medicine, including more than 3,000 types of manipulation interventions - catheterization, bronchoscopy, plasmapheresis, probing, etc., complex medical devices (anesthesia, cardiopulmonary bypass, the internal contour of which is difficult to disinfect, optical equipment).

To this we must add a twofold increase in the number of the elderly population with weakened immune reactivity due to age, frequent use of drugs, X-ray exposure and other reasons that violated the natural biocenosis.

11.2. IMMUNE REACTIVITY AND CHEMICALS

Chemical substances, the number of which reaches 4 billion (63 thousand are used in everyday life), can enter the body and cause various disorders. These include general toxic and local irritant effects, desquamation of the epithelium, bronchospasm, increased penetration of microorganisms through mechanical barriers. With chronic exposure, activation of CD8-lymphocytes is observed, which causes the development of immune tolerance, suppression of antibody formation, and inhibition of nonspecific anti-infective resistance factors.

The formation of conjugated antigens and the induction of reactions that deplete the immune system are possible. All these actions, except for the formation of immune deficiency, are also dangerous due to the mutagenic effect.

Immunotropic chemical compounds can be divided into the following groups.

1. Products of complete or partial combustion of fossil fuels - fly ash, toxic radicals, nitrogen peroxides, sulfur dioxide, polycyclic aromatic hydrocarbons, benzpyrenes, cholanthrenes.

2. Chemical industry products: benzene, phenols, xylene, ammonia, formaldehyde, plastics, rubber, paint and varnish products, petroleum products.

3. Household and agricultural chemicals, pesticides, insecticides, herbicides, fertilizers, detergents, cosmetics, medicines, flavors, detergents, etc.

4. Metals: lead, mercury, cobalt, molybdenum, etc.

5. Inorganic dust, quartz dioxide, asbestos, carbon, talc, polymetallic aerosols, welding fumes, etc.

Different chemicals trigger different mechanisms of damage to the immune system. For example, chlorinated cyclic dilexins, brominated biphenyls, methylmercury are the cause of impaired maturation of CD3 cells, thymus atrophy, lymph node hypoplasia; alkylating compounds, benzene, ozone, heavy metals - immunosuppression due to DNA damage, and aromatic amines, hydrazine - the formation of cytotoxic antibodies and cell clones against autolymphocytes. The use of halogen aromatic, ozone is accompanied by a decrease in the production of interleukins and interferons; chlorinated cyclic dilexins - functions of CD19 cells and the formation of antibodies; heavy metals, acridine dyes, hexachlorobenzene, aromatic amines - complement defects with a risk of developing SLE. Toxic nitrogen radicals, sulfur oxides, sulfur dioxide, quartz, coal, asbestos cause insufficiency of local immunity, phagocytosis, gastrointestinal tract, lungs, eyes; methylmercury, brominated biphings - suppression of the suppressor function of T-cells with hyperreactivity of CD3- and CD19-lymphocytes; aromatic amines, thiol poisons, mercury, heavy metals, methane - changes in the genotype of lymphocytes, solubilization of membrane HLA antigens, epitopes, CD and other receptors.

11.3. IMMUNE REACTIVITY AND OTHER FACTORS

Electromagnetic waves and microwave fields under chronic exposure cause phase fluctuations in the phagocytic activity of neutrophils, disruption of AT synthesis, which leads to immunopathological and immunosuppressive conditions.

Noise with an intensity of 60-90 dB for 2 months or more contributes to the inhibition of bactericidal and complementary activity.

blood serum, decrease in titers of normal and specific antibodies.

Various metals have a significant effect on the immune system. Beryllium, vanadium and iron induce, respectively, sensitization and modulation, stimulation of lymphoproliferation and modulation, inhibition of phagocytosis and antibody formation; gold, cadmium, potassium and cobalt - inhibition of chemotaxis and release of enzymes from phagocytes; suppression of the humoral immune response; CD3 lymphopenia, decreased DTH and NK cell activity; induction of HNT, HRT. Lithium, copper, nickel, mercury can cause suppression of leukocyte activity; decreased function of CD3 and CD19 cells; thymus involution and allergies; induction of autoimmune reactions and thymus atrophy, respectively. Finally, there are reports that selenium and zinc can cause modulation and, accordingly, thymus hypoplasia and the development of immunodeficiencies.

11.4. IMMUNE REACTIVITY AND REGIONAL

PECULIARITIES

There is a certain relationship between meteorological factors and indicators of nonspecific anti-infective resistance. The increase in the complementary activity of blood serum turned out to be closely associated with an increase in atmospheric pressure, and the production of lysozyme throughout the year - with changes in air temperature and its relative humidity. The level of β-lysines in the blood turned out to be associated with all weather factors, but air temperature had the highest degree of correlation with these indicators.

It is known that each individual is adapted to the usual conditions of life and, when changing his place of residence, adapts to a new environment for a long time. So, immigrants from areas with a hot or temperate climate to the north or northerners to the south experience suppression of immune reactivity during the year, which causes them to have an increased incidence of the upper respiratory tract, acute intestinal disorders with a sluggish course and an increase in protracted and chronic forms.

On the other hand, in areas with a cold climate, there is a decrease in the severity of allergic diseases, which is associated with fewer allergens in the environment. At the same time, in persons with a predisposition to allergies, cold air, windy weather cause attacks of asthmatic bronchitis, bronchitis.

al asthma, the occurrence of dermatoses, urticaria. In part, pathological reactions are due to the release into the blood of cold agglutinins, complete and incomplete autoantibodies against skin tissues and internal organs. The change in the immune reactivity of persons who have arrived to live in the Arctic and Antarctic regions is determined not only by the effect of low temperature, but also by the lack of ultraviolet radiation, malnutrition, etc.

When examining the immune status of about 120 thousand healthy individuals from 56 cities and 19 territorial regions of the CIS, several types of immune status were established. So, immune status with suppression of T-cell immunity found in residents of Norilsk, regions of the Far North, Krasnoyarsk Territory, the city of Kurchatov, Semipalatinsk Region, Novokuznetsk, Tbilisi, suppressive type of immune status - in the city of Serzhal, Semipalatinsk region and Vitebsk, immune status with suppression of humoral immunity - among residents of some cities and towns of the Central Asian region, as well as - Moscow, St. Petersburg, Chelyabinsk. A uniformly activated type of immune status with some stimulation of the cellular and humoral link was established in the cities of Kirishi and Odessa. An activated profile due to humoral mechanisms with normal or slightly reduced cellular reactions was registered in residents of Rostov-on-Don, Tashkent region, Nizhny Novgorod, Karaganda, Yerevan. Mixed type of immune status with suppression of cellular and activation of humoral immunity - in Kyiv, Armavir, Karakalpakstan.

11.5. IMMUNE REACTIVITY AND NUTRITION

Moderate manifestations of malnutrition do not cause profound damage to immune reactivity. However, in chronic protein-calorie deficiency, there is a decrease in the activity of phagocytosis, the properdino-complementary system, the formation of interferon, lysozyme, γ-globulins of various classes, a decrease in the content of CD3- and CD19-lymphocytes, their subpopulations, and an increase in the number of immature null cells.

Deficiency of retinol, riboflavin, folic acid, pyridoxine, ascorbic acid, iron reduces the resistance of tissue barriers, and in combination with a lack of protein inhibits the activity of cellular and humoral immunity. In individuals with hypo-

vitamin deficiencies, infectious diseases occur more often, are more severe, prone to chronicity and complications.

Exclusion from the diet of animal proteins leads to inhibition of humoral defense mechanisms. On the other hand, the lack of nucleic acids, even with sufficient caloric intake, leads to the suppression of cellular immunity. It should be emphasized that fasting, including therapeutic, to a certain extent reproduces the above effects.

11.6. IMMUNE REACTIVITY DURING EXPOSURE TO IONIZING RADIATION

The widespread use of nuclear technology entails an expansion of the circle of people exposed to the adverse effects of radiation factors, to which should be added the contingent living in areas contaminated with radionuclides after the Chernobyl accident.

Irradiation of the body causes an increase in the permeability of the skin, subcutaneous fat, pulmonary, blood-brain and hemato-ophthalmic barriers, intestinal vessels in relation to various microorganisms, decay products of autologous tissues, etc. These processes contribute to the development of complications. Violation of permeability begins in the first hours after radiation injury at a dose of 100 roentgens or more, reaches a maximum after 1-2 days. All this contributes to the formation of autoinfections.

A common characteristic feature of the irradiated organism is the prolongation of the period of purification from pathogens, the tendency to generalized infections, and resistance to opportunistic microorganisms (Escherichia coli, Proteus, sarcins, etc.) is especially strongly reduced. Reduced resistance to bacterial toxins Cl. perfringens, Cl. tetani, Cl. botulinum, diphtheria, staphylococcus, shigella. This is based on a decrease in the ability of blood serum to neutralize toxins, as well as damage to the function of the pituitary gland, adrenal glands, and thyroid gland.

Representatives of normal automicroflora living in natural cavities (intestines, respiratory tract), as well as pathogens located in various foci of infection, if any, migrate into the blood, spread to organs. At the same time, the composition of normal microflora changes dramatically,

Species immunity is highly stable to the influence of ionizing radiation.

With regard to specific immunity, irradiation with lethal and sublethal doses before immunization causes a sharp suppression of the formation of antibodies during the first two days, which lasts up to 7 days or more. Inhibition of antibody production is combined with a significant prolongation of the inductive phase of antibody genesis from 2–3 days in the norm to 11–18 days. As a result, the maximum production of antibodies is registered only 40-50 days after irradiation. However, complete inhibition of the synthesis of specific immune globulins does not occur.

If irradiation is carried out after immunization, then the synthesis of antibodies either does not change or slows down slightly. Installed two phases of antibody production under the influence of ionizing radiation. First - radiosensitive, lasting 1-3 days, second - radioresistant, making up the rest of the time period.

Revaccination is quite effective with primary immunization carried out before exposure.

Irradiation of an immunized organism, produced at the height of antibody production, can short-term (several times) reduce the number of circulating antibodies, but after a day (less often two), it is restored to its original values.

Chronic exposure in the same dose as acute exposure before vaccination damages the immune system to a much lesser extent. In some cases, to obtain the same effect, its total dose may exceed a single "acute" dose by more than 4 times.

Ionizing radiation also causes suppression of transplantation immunity. The closer the irradiation is applied to the time of transplantation, the more damage to transplant immunity occurs. With the lengthening of this interval, the inhibitory effect decreases. The normalization of the transplantation reaction of the organism occurs, as a rule, 30 days after exposure.

To a lesser extent, the formation of a secondary transplantation response suffers. As a result, secondary grafts in irradiated contingents are rejected much faster than primary ones.

Ionizing radiation, suppressing the immune system of the recipient

that significantly lengthens the period of immune inertness or tolerance. For example, when bone marrow is transplanted to irradiated persons, the transplanted cells proliferate intensively during the period of immune tolerance caused by irradiation and replace the destroyed hematopoietic tissue of the recipient. There is a chimera organism, because. the hematopoietic tissue in such an organism is the tissue of the donor. All this leads to a prolongation of the engraftment of the donor tissue and the possibility of transplanting other tissues of the donor. On the other hand, radiation can break the formed tolerance. Most often, incomplete non-response suffers, while complete non-response is more radioresistant.

Passive immunity is more resistant to radiation. The timing of the withdrawal of passively administered immune globulins from the irradiated organism, as a rule, does not change. However, their therapeutic activity drops sharply. This makes it necessary to administer 1.5-8 times higher doses of serum or γ-globulins to the corresponding contingents in order to achieve the proper preventive or therapeutic effect.

Irradiation also changes the antigenic composition of tissues. This causes the disappearance of some normal antigens, i.e. simplification of the antigenic structure and the emergence of new antigens. Species antigenic specificity does not suffer from irradiation, organ and organoid specificity changes. The appearance of autoantigens is nonspecific in relation to the radiation factor. Tissue destruction and the appearance of autoantigens are observed within a few hours after irradiation. In some cases, their circulation persists for 4-5 years.

Most of the lymphocytes are highly sensitive to radiation, and this manifests itself already when exposed to external radiation at a dose of 0.5 to 10.0 Gy (in principle, internal radiation has the same effect). Cortical thymocytes, splenic T-cells and B-lymphocytes are the most sensitive to exposure. More resistant are CD4 cells and T-killers. These data substantiate the high risk of autoimmune complications after external and incorporated irradiation.

One of the manifestations of the functional inferiority of irradiated lymphocytes is the violation of their cooperative capabilities. For example, in the first days (1-15 days) after the Chernobyl accident, there was a decrease in the number of cells with the CD2DR+ phenotype. At the same time, there was a decrease in thymic serum titer

factor and indicator RTML with Con-A. All this is evidence of inhibition of the functional activity of the T-system of immunity. Changes in the humoral link were less pronounced.

Small doses of radiation, as a rule, do not cause gross morphological changes in the immune system. Their effect is realized mainly at the level of functional disorders, the recovery of which occurs very slowly and is cyclical. For example, in irradiated contingents, there is a decrease in the amount of CD2DR+, which is eliminated only after 1-12 months, depending on the dose received. In some cases, even after 2 years, there was a persistence of a secondary immunodeficiency state.

In addition to the negative effect of the radiation factor on lymphocytes, the auxiliary cells of the immune system are damaged. In particular, the stroma, thymic epithelial cells are affected, which leads to a decrease in the production of thymosin and other thymic factors. As a result, sometimes even after 5 years, there is a decrease in the cellularity of the thymus cortex, a disorder in the synthesis of T-cells, the function of the peripheral organs of the lymphoid system is weakened, and the number of circulating lymphocytes is reduced. At the same time, antibodies are formed against thymus tissue, which leads to "radiation aging" of the immune system. There is also an increase in IgE synthesis, which increases the risk of developing allergic and autoimmune processes in the irradiated organism.

Evidence of the negative effect on the immune system of exposure is the change in the incidence of the inhabitants of Kyiv after the accident at the Chernobyl nuclear power plant. Thus, from 1985 to 1990, the incidence per 10,000 population increased: bronchial asthma - by 33.9%, bronchitis - by 44.2%, contact dermatitis - by 18.3%.

Characteristic was the formation of the following clinical syndromes.

1. Increased susceptibility to respiratory infections, especially in patients with bronchial asthma and bronchitis, with an allergic component. The presence of inflammatory processes of an infiltrative nature in the lungs, subfebrile conditions, skin allergic reactions.

2. Hemorrhagic systemic vasculitis, lymphadenopathy, polymyalgia, polyarthralgia, fever of unknown origin, severe general weakness, mainly in young people.

3. "Syndrome of mucous membranes." This is burning, itching of mucous membranes of various localization (eyes, pharynx, oral cavity, genitals) in combination with an astheno-neurotic condition. At the same time, there are no visible changes in the mucous membranes. Microbiological examination of the mucous membranes reveals conditionally pathogenic microflora, more often staphylococcal and fungi.

4. Syndrome of multiple intolerance to a wide range of substances of various nature (food, drugs, chemicals, etc.). This is most often observed in young women in combination with pronounced signs of autonomic dysregulation and asthenic syndrome.

Effects of radiation on the immune system and their consequences

Ionizing radiation in any dose causes functional and morphological changes in cellular structures and changes the activity in almost all body systems. As a result, the immunological reactivity of animals is increased or inhibited. The immune system is highly specialized, it consists of lymphoid organs, their cells, macrophages, blood cells (neutrophilic, eosinophilic and basophilic, granulocytes), complement system, interferon, lysozyme, properdin and other factors. The main immunocompetent cells are T - and B-lymphocytes responsible for cellular and humoral immunity.

The direction and degree of changes in the immunological reactivity of animals under the action of radiation is determined mainly by the absorbed dose and the power of irradiation. Small doses of radiation increase the specific and non-specific, cellular and humoral, general and immunobiological reactivity of the body, contribute to the favorable course of the pathological process, increase the productivity of livestock and birds.

Ionizing radiation in sublethal and lethal doses leads to the weakening of animals or the suppression of the immunological reactivity of animals. Violation of the parameters of immunological reactivity is noted much earlier than the clinical signs of radiation sickness appear. With the development of acute radiation sickness, the immunological properties of the body are increasingly weakened.

The resistance of the exposed organism to infectious agents decreases due to the following reasons: impaired permeability of tissue barrier membranes, reduced bactericidal properties of blood, lymph and tissues, suppression of hematopoiesis, leukopenia, anemia and thrombocytopenia, weakening of the phagocytic mechanism of cellular defense, inflammation, inhibition of antibody production and other pathological changes in tissues and organs.

Under the influence of ionizing radiation in small doses, the permeability of tissues changes, and with a sublethal dose and more, the permeability of the vascular wall, especially capillaries, increases sharply. After irradiation with medium lethal doses, animals develop an increased permeability of the intestinal barrier, which is one of the reasons for the settlement of intestinal microflora in organs. Both with external and internal irradiation, an increase in the autoflora of the skin is noted, which manifests itself early, already in the latent period of radiation injury. This phenomenon can be traced in mammals, birds and humans. Increased reproduction and settlement of microorganisms on the skin, mucous membranes and organs is caused by a decrease in the bactericidal properties of liquids and tissues.

Determining the number of Escherichia coli and especially hemolytic forms of microbes on the surface of the skin and mucous membranes is one of the tests that allows you to early determine the degree of impaired immunobiological reactivity. Usually, an increase in autoflora occurs synchronously with the development of leukopenia.

The pattern of changes in the autoflora of the skin and mucous membranes under external irradiation and the incorporation of various radioactive isotopes is preserved. With general exposure to external sources of radiation, zoning of the violation of bactericidal skin is observed. The latter, apparently, is associated with the anatomical and physiological characteristics of various areas of the skin. In general, the bactericidal function of the skin is directly dependent on the absorbed dose of radiation; at lethal doses, it sharply decreases. In cattle and sheep exposed to gamma rays (cesium-137) at a dose of LD 80-90/30, changes in the autoflora of the skin and mucous membranes begin from the first day, and the initial state in surviving animals comes on the 45-60th day.

Internal irradiation, like external irradiation, causes a significant decrease in the bactericidal activity of the skin and mucous membranes with a single administration of iodine-131 to chickens at doses of 3 and 25 mCi per 1 kg of their weight, the number of bacteria on the skin begins to increase from the first day, reaching a maximum on the fifth day. Fractional command of the specified amount of the isotope for 10 days leads to a significantly large bacterial contamination of the skin and oral mucosa with a maximum on the 10th day, and the number of microbes with increased biochemical activity increases. In the next time, there is a direct connection between the numerical increase in bacteria and the clinical manifestation of radiation injury.

One of the factors that provide natural antimicrobial resistance of tissues is lysozyme. With radiation injury, the content of lysozyme in tissues and blood decreases, which indicates a decrease in its production. This test can be used to detect early changes in resistance in exposed animals.

Phagocytosis plays an important role in the immunity of animals to infections. With internal and external irradiation, in principle, changes in the phagocytic reaction have a similar picture. The degree of violation of the reaction depends on the magnitude of the dose of exposure; at low doses (up to 10-25 rad) there is a short-term activation of the phagocytic ability of phagocytes, with semi-lethal - the activation phase of phagocytes is reduced to 1-2 days, then the activity of phagocytosis decreases and in lethal cases reaches zero. In recovering animals, a slow activation of the phagocytosis reaction occurs.

The phagocytic abilities of the cells of the reticuloendothelial system and macrophages undergo significant changes in the irradiated organism. These cells are quite radioresistant. However, the phagocytic ability of macrophages under irradiation is disturbed early. The inhibition of the phagocytic reaction is manifested by the incompleteness of phagocytosis. Apparently, irradiation breaks the connection between the processes of capture of particles by macrophages and enzymatic processes. Suppression of the function of phagocytosis in these cases may be associated with inhibition of the production of the corresponding opsonins by the lymphoid system, because it is known that in radiation sickness there is a decrease in the blood of complement, properdin, opsonins and other biological substances.

Autoantibodies play an important role in the immunological mechanisms of self-defense of the organism. With radiation damage, there is an increase in the formation and accumulation of autoantibodies. After irradiation, immunocompetent cells with chromosomal translocations can be detected in the body. In genetic terms, they differ from normal cells of the body, i.e. are mutants. Organisms in which there are genetically different cells and tissues are referred to as chimeras. Formed under the action of radiation, abnormal cells responsible for immunological reactions acquire the ability to produce antibodies against normal body antigens. The immunological reaction of abnormal cells against their own body can cause splenomegaly with atrophy of the lymphoid apparatus, anemia, retardation in growth and weight of the animal, and a number of other disorders. With a sufficiently large number of such cells, the death of the animal can occur.

According to the immunogenetic concept put forward by the immunologist R.V. Petrov, the following sequence of radiation injury processes is observed: mutagenic effect of radiation → relative increase in abnormal cells that have the ability to aggression against normal antigens → accumulation of such cells in the body → autogenic aggression of abnormal cells against normal tissues. According to some researchers, autoantibodies that appear early in an irradiated organism are involved in an increase in its radioresistance during single exposures to sublethal doses and during chronic irradiation with low doses.

Leukopenia and anemia, suppression of the activity of the bone marrow and elements of the lymphoid tissue testify to the violation of resistance in animals during irradiation. Damage to blood cells and other tissues and a change in their activity affect the state of humoral immunity systems - plasma, fractional composition of serum proteins, lymph and other fluids. In turn, these substances, when exposed to radiation, affect cells and tissues and in themselves determine and supplement other factors that reduce natural resistance.

Inhibition of non-specific immunity in irradiated animals leads to an increase in the development of endogenous infection - the number of microbes in the autoflora of the intestine, skin and other areas increases, its species composition changes, i.e. dysbacteriosis develops. Microbes - inhabitants of the intestinal tract - begin to be detected in the blood and internal organs of animals.

Bacteremia is extremely important in the pathogenesis of radiation sickness. Between the onset of bacteremia and the period of death of animals there is a direct relationship.

With radiation damage to the body, its natural resistance to exogenous infections changes: tuberculosis and dysentery microbes, pneumococci, streptococci, pathogens of paratyphoid infections, leptospirosis, tularemia, trichophytosis, candidiasis, influenza viruses, influenza, rabies, poliomyelitis, Newcastle disease (highly contagious viral disease of birds from order chicken, characterized by damage to the respiratory, digestive and central nervous system), protozoa (coccidia), bacterial toxins. However, species immunity of animals to infectious diseases is preserved.

Radiation exposure in sublethal and lethal doses aggravates the course of an infectious disease, and infection, in turn, aggravates the course of radiation sickness. With such options, the symptoms of the disease depend on the dose, virulent and temporal combination of factors. At radiation doses that cause a severe and extremely severe degree of radiation sickness, and when animals are infected, the first three periods of its development (the period of primary reactions, the latent period and the height of the disease) will mainly be dominated by signs of acute radiation sickness. Infection of animals with the causative agent of an acute infectious disease shortly or against the background of irradiation with sublethal doses leads to an aggravation of the course of this disease with the development of relatively characteristic clinical signs. So, in piglets irradiated with lethal doses (700 and 900 R) and infected after 5 hours, 1,2,3,4, and 5 days. after irradiation with the plague virus, at autopsy, mainly changes are found that are observed in irradiated animals. Leukocyte infiltration, cell proliferative reaction, splenic infarcts observed in the pure form of plague are absent in these cases. Increased sensitivity of gilts to the causative agent of erysipelas in patients with radiation sickness of moderate severity persists after 2 months. after irradiation with X-rays at a dose of 500 R. During experimental infection with the erysipelas pathogen, the disease in pigs manifests itself more rapidly, the generalization of the infectious process occurs on the third day, while in control animals it is usually recorded only on the fourth day. Pathological changes in irradiated animals are characterized by pronounced hemorrhagic diathesis.

Experimental studies on guinea pigs and sheep revealed a peculiar course of anthrax in animals with moderate radiation sickness. Both externally and combined exposure to radiation reduces their resistance to infection by the causative agent of this disease. Clinical signs are not strictly specific for either radiation sickness or anthrax. Severe leukopenia is noted in patients, body temperature rises, pulse and respiration become more frequent, the function of the gastrointestinal tract is disturbed, anthrax antibodies in low titers, detected by the indirect hemagglutination reaction, appear in the blood serum. The disease is acute and ends fatally. At pathological autopsy, in all cases, a decrease in the spleen and seeding with anthrax microbes of internal organs and lymph nodes is recorded.

Consequently, the impact of ionizing radiation on animals in sublethal doses in lethal doses causes a decrease in all natural factors of the body's resistance to endogenous and exogenous infections. This is manifested by the fact that in irradiated animals the onset of infectious diseases occurs at a lower dose of the pathogen, among the irradiated animals the percentage of sick people increases, the disease ends faster and more often in death.

Violation of immunobiological reactivity occurs already during the period of primary reactions to radiation and, gradually increasing, reach a maximum of development in the midst of radiation sickness. In surviving animals, the natural factors of immunity are restored, the completeness of which is determined by the degree of radiation injury.

It should be noted that with regard to the effect of ionizing radiation on the factors of natural immunity, there is still a lot of unexplained, in particular, the issues of the sequence of their inhibition, the significance of each of them in various infections and in different animals, the possibility of their compensation and activation are poorly studied.

Radiation immunology studies the effect of ionizing radiation on the immune system. In more detail, radiation immunology studies disorders and methods of restoring antimicrobial immunity, the features of the interaction of the irradiated organism with microbes, the role of infectious complications and autoimmune mechanisms in the pathogenesis, treatment and outcome of radiation sickness, the effect of radiation on transplant immunity, problems associated with the emergence of so-called radiation chimeras, with the possibility of overcoming biological incompatibility in the irradiated organism, using transplantation of cells of hematopoietic organs for the treatment of radiation sickness (see).

The effect of ionizing radiation on immunological reactivity is manifested in a sharp inhibition of the main mechanisms of immunity. The permeability of biological barriers increases, the bactericidal activity of blood and tissues decreases, the phagocytic activity of cells decreases, and the formation of antibodies is sharply inhibited. In acute radiation sickness, the body is actually unarmed not only against pathogenic, but also conditionally pathogenic microorganisms. A constant companion of radiation sickness is an endogenous infection with bacteremia due to microbes - inhabitants of the intestines, respiratory tract, etc. The direct cause of the death of an irradiated organism is often autoinfection. Exogenous infectious diseases are very difficult, characterized by a generalization of the process and the accumulation of pathogens in tissues. Prevention and treatment of infectious complications is an obligatory measure in the complex therapy of radiation sickness.

As a result of the action of radiation on cells and tissues, their antigenic properties change. This circumstance and the circulation of tissue antigens in the blood lead to the appearance of autoantibodies and autosensitization. However, the significance of the autoimmune mechanism in the overall picture of radiation injury has not yet been finally elucidated.

Radiation immunology also deals with transplantation immunity. Irradiation, inhibiting transplantation immunity, ensures the engraftment and reproduction of cells of hematopoietic organs transplanted from a donor. However, due to the immunological competence of hematopoietic tissues, an immunological reaction of transplanted cells against host cells (“graft versus host”) is possible. This explains the development on the 4-8th week after transplantation of a "secondary disease", which manifests itself in animals with dermatitis, hair loss, exhaustion, leading to death. In humans, the "secondary disease" has similar symptoms. Many researchers also consider a host-versus-graft reaction likely. Radiation immunology seeks means to prevent the development of a "secondary disease", which is important not only for the treatment of radiation sickness, but also in a broader sense for solving the problem of biological incompatibility of tissues.

Effects of radiation on the immune system and their consequences

Ionizing radiation in any dose causes functional and morphological changes in cellular structures and changes the activity in almost all body systems. As a result, the immunological reactivity of animals is increased or inhibited. The immune system is highly specialized, it consists of lymphoid organs, their cells, macrophages, blood cells (neutrophilic, eosinophilic and basophilic, granulocytes), complement system, interferon, lysozyme, properdin and other factors. The main immunocompetent cells are T- and B-lymphocytes responsible for cellular and humoral immunity.

Phagocytosis plays an important role in the immunity of animals to infections. With internal and external irradiation, in principle, changes in the phagocytic reaction have a similar picture. The degree of violation of the reaction depends on the magnitude of the dose of exposure; at low doses (up to 10–25 rad), a short-term activation of the phagocytic ability of phagocytes is noted, with semi-lethal doses, the activation phase of phagocytes is reduced to 1–2 days, then the activity of phagocytosis decreases and in lethal cases reaches zero. In recovering animals, a slow activation of the phagocytosis reaction occurs.

Leukopenia and anemia, suppression of the activity of the bone marrow and elements of the lymphoid tissue testify to the violation of resistance in animals during irradiation. Damage to blood cells and other tissues and changes in their activity affect the state of humoral immune systems - plasma, fractional composition of serum proteins, lymph and other fluids. In turn, these substances, when exposed to radiation, affect cells and tissues and in themselves determine and supplement other factors that reduce natural resistance.

Inhibition of non-specific immunity in irradiated animals leads to an increase in the development of endogenous infection - the number of microbes in the autoflora of the intestine, skin and other areas increases, its species composition changes, i.e. dysbacteriosis develops. In the blood and internal organs of animals, microbes - inhabitants of the intestinal tract - begin to be detected.

Bacteremia is extremely important in the pathogenesis of radiation sickness. Between the onset of bacteremia and the period of death of animals there is a direct relationship.