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Introduction. An urgent direction is the search for means that increase the effectiveness of the Y. pestis EV NIIEG vaccine and reduce the side pathological manifestations caused by it. Organoselenium compounds have immunotropic properties and increase the antioxidant potential of the body, as well as have an antidystrophic effect and an antiallergic effect. Materials of the study of the immunomodulating effect of the experimental selenium-containing compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the macroorganism of laboratory animals are presented.The aim. To evaluate the effect of the organoselenium compound 974zh on the structural rearrangement of the organs of experimental animals in the dynamics of the vaccine process caused by Y. pestis EV.Methods. The study was carried out on 70 certified outbred white mice. Histological material (thymus, lymph nodes, spleen, adrenal glands, liver) was embedded in paraffin, semi-thin sections were stained with hematoxylin and eosin, thionin, and by the Brachet method. The severity of pathological changes in the liver and adrenal glands, proliferation of plasma cells and structural changes in immunocompetent organs (thymus, lymph nodes and spleen) were assessed. Microphotography and quantitative analysis were performed using MoticImagesPlus 2.0. Statistical processing was carried out using the computer program Statistica.Results. It has been established that the combined administration of 974zh and Y. pestis EV leads to morphological and functional restructuring of immunocompetent organs, enhances the proliferation of plasma cells in the spleen and lymph nodes, and eliminates negative changes in the liver and adrenal glands. Conclusion. Thus, the 974zh preparation enhances the immunogenic effect of the Y. pestis EV vaccine strain, increasing the T- and B-dependent zones of the spleen and lymph nodes, increasing the proliferation of plasma cells, and also significantly reduces pathological changes in the liver and adrenal glands.

Background. The current direction is the study of anatomical and histological changes caused by the causative agent of anthrax with a different plasmid profile. It was found that Bacillus anthracis strains with the same set of plasmids and the same morphological, serological and cultural properties sometimes have different pathogenicity.Aim of the study. Comparative analysis of anatomical and histological changes in the organs of experimental animals in the dynamics of the infectious process caused by the pathogen B. anthracis with different genotypes.Methods. Four strains were used as the study object: B. anthracis I-275 (pCO1–/ pCO2–), B. anthracis I-323 (pCO1–/ pCO2–), B. anthracis I-217 (pCO1+/pCO2– and B. anthracis 34F Stern pCO1+/pCO2–). The study was conducted on 260 certified white mice. Histological material was embedded in paraffin, semi-thin sections were stained with hematoxylin-eosin, thionine, and according to Brachet. The severity of pathological changes, the presence of the pathogen, and the proliferation of plasma cells were evaluated. The changes detected during the autopsy of the animal and the results obtained during the histological examination of the anatomical material were analyzed and generalized. Microphotography and quantitative analysis of plasma cells were performed using the “Motic Images Plus 2.0” application software package. Statistical processing of the obtained data was performed using the computer program “Statistics”, version 6 (Novosibirsk). The results were considered reliable if the probability of error was less than 0.05 (p < 0.05) in relation to the control.Results. Differences in anatomical and histological changes in organs and tissues of white mice infected with B. anthracis with the same set of plasmids were revealed. It was found that in animals infected with non-plasmid strains of B. anthracis, the proliferation of plasma cells is significantly reduced compared to animals infected with singleplasmid strains of the anthrax pathogen.Conclusion. The obtained data suggest that the revealed differences are related to the plasmid profile of the studied strains, but also to the peculiarities of their enzymatic activity, adhesion ability, and other factors. Thus, anthrax strains that have the same morphological, serological and cultural properties sometimes have different virulence. And also, anthrax strains that have lost virulence lose their immunogenicity, as evidenced by the ratio of plasma cells.

Introduction. The current direction in medicine is the creation of immunobiological preparations to increase the effectiveness of specific immunotherapy and immunoprophylaxis, containing immunomodulators in their composition. These natural or synthetic substances can have a regulating effect on the immune system. At present, water-soluble organic-inorganic polymeric materials with nanoparticles of various chemical substances with bactericidal and immunomodulating properties can serve as such promising compounds.The aimof the work is to study the acute toxicity of polymer nanocomposites based on 1-vinil-1,2,4-triazole copolymer with N-vinylpyrrolidone with silver, gold and selenium nanoparticles and their effect on the functional state of immune system cells in vitro.Materials and methods.The study of acute toxicity was performed on outbred white mice. The activity of superoxide dismutase and glucose-6-phosphate dehydrogenase were studied in guinea pig peritoneal macrophages. The study of spontaneous and nanocomposite-induced production of pro- (interferon gamma and tumor necrosis factor alpha) and anti-inflammatory (interleukin-4) cytokines by blood cells was carried out using clinical material obtained from volunteers using the ELISA method. Results. It has been established that nanocomposites with silver and gold nanoparticles do not cause the death of white mice, their temperature increase and body weight decrease. The average lethal dose for a nanocomposite with selenium nanoparticles was determined as 1 gram per 1 kilogram of animal mass. It was shown that the tested nanocomposites have a stimulating effect on the production of cytokines by human blood cells in vitro. It was established that a nanocomposite with selenium nanoparticles increases the activity of superoxide dismutase and glucose-6-phosphate dehydrogenase. A comparative analysis of their actions with the actions of commercial preparations of biological origin, with immunomodulatory properties.Conclusion. The data obtained allow us to substantiate the need for further research on the effects of nanocomposites based on 1-vinyl-1,2,4-triazole copolymer with N-vinylpyrrolidone with silver, gold and selenium nanoparticles on the macroorganism in both in vitro and in vivo conditions.

The creation of immuno-biological drugs to increase the effectiveness of specific immunotherapy and immunoprophylaxis is a current trend in medicine to date. Therefore, the search and development of new safe and effective artificial bioorganic complexes (immunomodulators) capable of stimulating individual responses of immune system to reduce infectious morbidity is an important area of research. At the moment, such promising preparations can be considered water-soluble polymeric materials and organo-inorganic polymer nanocomposites with nanoparticles of various metals which possess immunomodulating and bactericidal properties. The study results of the effects of 1-vinyl-1,2,4-triazole copolymer with N-vinylpyrrolidone and nanocomposites based on it with gold and silver nanoparticles on acute toxicity and functional state of immunophagocytic cells of experimental animals, as well as the production of IFN-γ, TNF-α and IL-4 by human blood lymphocytes are represented in this article. It was established that the tested preparations do not cause increase in body temperature, decrease in mass and death of animals. It was shown that they also have the multidirectional action on cytokine production by human blood cells in vitro, the ability to increase activity of оxidative stress-related enzymes and antioxidant protection of phagocytes. The data obtained by us allow to explain the need for further investigation of the actions of nanocomposites and copolymer in vitro and in vivo.

Live vaccines are used for specific brucellosis prophylaxis in the Russian Federation. These vaccines in addition to a number of positive properties have some limitations including high agglutinogenicity, reactogenicity, sensitizing activity. In this connection, the development of subunit vaccines without adverse reactions is a perspective direction in modern vaccinology. Complex morphological research of the adrenal glands and comparative analysis of peripheral blood (leukogram, leukocytic index and index of allergization) of white mice immunized with thermoextracts (ТE) of Brucella abortus I-206 in L- and S-form and inactivated vaccine B. abortus 19 ВА were conducted. It was shown that ТE unlike B. abortus 19 ВА caused minor alterations in peripheral blood of the experimental animals in early periods of observation (increase of allergization index, changes in leukogram) with the subsequent levelling to the values in control. Expositions of the adrenal gland zoning were determined and cellular structure was estimated in consideration of morphometry. Changes in architectonics of the mice organ immunized with B. abortus 19 ВА were revealed. These alterations could indicate the stress-reaction development. In case of ТE application the given changes were insignificant and were developed in early periods. The revealed morphological changes in adrenal glands of laboratory animals permit to prove the necessity of realization the further experimental researches to ТE application as the components for development of a subcellular brucellosis vaccine.

At present, development of effective vaccines of new generation is an actual problem, in particular concerning the tularemia causative agent. It determines the need to search antigen determinants with high immunogenic activity. Some authors demonstrate that outer membrane proteins of Francisella tularensis possess immunological activity. This fact gave occasion to isolation and comprehensive study of F tularensis cellular envelopes as a perspective component in vaccine engineering. The influence of cell walls of F. tularensis was studied for morphological changes in immunocompetent organs of experimental animals. Cell walls were obtained from three virulence strains of living cultures: F. tularensis subsp. mediaasiatica А-61, F. tularensis subsp. nearctica В-399 A-Cole, F. tularensis subsp. holarctica 306 and vaccine strain F. tularensis subsp. holarctica 15 (extracted by Research Institute of Epidemiology and Hygiene). Cell walls of different subspecies of F. tularensis stimulate the production of antibody forming cells and cell proliferation more in T-dependent zones of lymph nodes and spleen. It has been determined that these antigen preparations do not cause stress reaction of the experimental animal organisms. Basing on the findings, we made a conclusion that there is a need for further detailed investigation of immunogenic properties of CE F. tularensis subsp. holarctica 306, F. tularensis subsp. mediasiatica А-61 and F. tularensis subsp. tularensis B-399 A-Cole as perspective components in development of tularemia vaccines.

Data of histological study of pathomorphological changes in liver of white mice with experimental plague are represented in the article. An important element in evaluation and prediction of the pathological process in the liver is the analysis of hepatocyte karyokinesis, the mitotic index calculation, the counting number of atypical mitosis and the degree of organ regeneration ability. Dynamics of these liver changes at infection process in experimental animals caused by Yersinia pestis plasmid variants was investigated in this work. The variability of liver injuries was shown depending on plasmid-associated virulence of the infection agent. It was proved that the Y. pestis strain carrying three basic pYP (6 mDa), pYV (45 mDa), pYT (61 mDa) plasmids caused the most severe systemic disease with lethal outcome as a rule. Lack of species-specific plasmids and especially virulence and pathogenicity plasmids reduced the rate of infection process generalization and the ability of the pathogen to initiate pathological changes incompatible with the microorganism life. Therefore, all morphological liver changes in experimental plague infection are directly dependent on plasmid profile of the pathogen. The mechanism of toxicity included the damaging effect of the toxin to the cellular structures and failure of the metabolic processes in the organism. Acuity of intoxication and the development of pathological process can be estimated by exploring changes in liver morphology.

Experimental data concerning complex study of antioxidant activity of Y. pestis with different plasmid spectrum (wild-type Yersinia pestis subsp. pestis, Yersinia pestis subsp. altaica and their isogenic variants) are represented in the article. Superoxide dismutase activity of the tested Y. pestis strains was from 6.0 to 9.0 x 109 microbe cells. Significant differences between the Y. pestis strains with different plasmid composition were not detected by this parameter. Our results, consistent with the data of other authors, tell that superoxide dismutase activity is a thermo-inducible feature and does not depend on a plasmid spectrum. High peroxide destroying activity was also detected in all tested Y. pestis strains. The differences between the strains regarding their common peroxide destroying activity were found. This parameter of the plague microbe strains lacking pYP plasmid was at least 3 times lower than common peroxide destroying activity in strains with this plasmid in the genome. In our opinion these revealed differences were caused by characteristics of plasmid spectrum. The common peroxide destroying activity's degree of Y. pestis strains can be associated with the presence of pYP plasmid in the genome. The isogenic variants of Y. pestis strains lacking one of the plasmids had smaller pathogenic activity. This fact points to the need for further study of these strains.

The article presents the research results of immunogenic potency of antigen preparation Bacillus anthracis Sterne 34F on the guinea pig model. It was found that a single inoculation of this preparation, before the contamination of virulent B. anthracis strain, protects 60-80 % of experimental animals. The metal-containing nanocomposites were used to improve the immunogenicity of this antigen preparation. The combined use of antigenic preparation S-2 with argentogalactomannan increases its immunogenic potency and conduces to the survival of experimental animals. Argentogalactomannan exhibits adjuvant properties enhanced the immunogenic features of the S-2 B. anthracis 34F2 Sterne that may indicate its availability as an adjuvant in the construction of chemical vaccines.

The article presents the results of the research of effect of metal-containing nanocomposites on the content of splenic Band T-lymphocytes of white mice. Phenotypic analysis of the spleen cells suspension was conducted by flow cytometry on BD FACSCanto ™ П. Stimulating effect of these medications on the immune response formation is showed and is proved by the increase of content of B-lymphocytes and T-helper cells and it indicates cooperative interactions between the cells of immune system. It was experimentally showed that the medications 2-N-HTP-Ag, GM-Ag can be recommended for the further research in order to increase protective properties of an organism.

The article presents the data on the influence of Yersinia pestis plasmid profile on subpopulation structure of mononuclear cells of peritoneal fluid of mice at the early stages of infectious process. It was showed that change of cellular composition of peritoneal fluid of the experimental animals depended on the plasmid profile of Yersinia pestis strains. The phase character in the changes of quantitative composition of the mast cells of peritoneal fluid of white mice infected with Y. pestis strains with different plasmid spectrum was determined.

Data of Yersinia pestis plasmid structure influence on its adhesive properties and phagocytic activity of peritoneal macrophages in vitro are represented. It is shown that Y. pestis strains of diverse subspecies differing by a plasmid profile, particularly by one of the plasmids (pYP, pYV) lacking, possess low adhesive activity and promote the increase of laboratory animal phagocyte absorbing capacity.

Influence of Francisella tularensis lipopolysaccharide preparations on morphological changes in immunocompetent experimental animals was studied by subcutaneous introduction using survey microscopy and morphometric methods. Low expressed activation of B- and T-dependent bands in immunocompetent organs was determined. Proliferation of antigen-presented cells at early stages of investigation indicates the cell immunity activation. Pathomorphological alterations caused by lipopolysaccharide inoculation are homogeneous and benignant.

We studied influence of silver-containing nanocomposites — galactomannan and poly-1-vinyl-1,2,4-triazole — on cell structure of peripheral blood and red marrow of white mice. The results obtained after the experiments testify that these nanocomposites aren't toxic, the changes caused by their introduction are productive and. part of them points at the activization of immune system of macroorganizm.

Influence of a cobalt-containing nanobiocomposite on basis of arabinogalactane on morphological changes in immunocompetent organs of the experimental animals at peroral and parenteral introduction was studied, by a computer program. «Morphometry». Comparative estimation, of morphological and. histological changes in spleen and. regional lymph, nodes of the outbred. white mice was performed.