[SOME ASPECTS OF NON-SPECIFIC PROPHYLAXIS AND THERAPY OF ESPECIALLY DANGEROUS INFECTIONS].

Recently, due to spread of dangerous and especially dangerous infections much attention is given to development of complex approaches to their prophylaxis and therapy. Data on use of immune modulators, cytokines, probiotics, preparations of plant origin for non-specific prophylaxis of especially dangerous infections are analyzed in the review, and expediency of their combined use with specific and emergency prophlaxis of these diseases is evaluated.

[Effect of neutrophilokines on functional activity of macrophages during formation of immunity against cholera].

AIM: To study effect of neutrophilokines on functional activity of macrophages (Mph) during formation of immunity against cholera. MATERIALS AND METHODS: In order to obtain peritoneal neutrophils (Nph), 2 ml of 0.1% glycogen solution in buffered with phosphates sodium chloride solution was administered intraperitoneally to 100 outbred mice. Vibrio cholerae 1130 in dose 10 microbial cells/Nph and cholera toxin (CT) in dose 1 or 10 mcg/ ml were used as inducers of neutrophilokines synthesis. Obtained neutrophilokines were assessed on their effect on phagocytic activity of Mph, resistance of these cells to cytotoxic and apoptogenic effects of Vibrio cholerae and CT as well as effect on lysosomal apparatus of Mph. RESULTS: It was established that neutrophilokines induced by Vibrio cholerae and CT stimulate killer activity of Mph and lability of their lysosomal membranes, and suppress programmed death of these cells. CONCLUSION: Results of studies revealed immunoregulatory activity of neutrophilokines relative to Mph and demonstrated ability for cooperation between mono- and polynuclear phagocytes mediated by cytokines and, in particular, neutrophilokines.

[Evaluation of the immunoregulatory activity of neutrophilokine fractions in a macrophage model].

A procedure was proposed to evaluate the immunoregulatory activity of neutrophilokine fractions on a model of macrophages. It was established that all the fractions studied did not affect the absorptive capacity of these cells in both primary and secondary immune responses. At the same time, the majority of neutrophilokine fractions modulated the killer activity of macrophages: they potentiated or inhibited it. The proposed procedure for evaluating the regulatory effect of individual neutrophilokine fractions on a model of studying the killer activity makes it possible not only to characterize their activity, but also to identify helper and suppressor fractions, which discloses approaches to correcting an immune response by means of these fractions.

[Influence of neutrophilokines on population and subpopulation repertoire of lymphocytes and their functional activity during immune response against plague].

Results of experimental study of regulatory effect of nutrophilokines induced by Yersinia pestis EV strain on population and subpopulation repertoire of lymphocytes and their functional activity during immune response against plague infection are presented. It was established that these neutrophilokines stimulate CD4+ and suppress CD8+ lymphocytes. Helper effect of neutrophilokines on functional activity of lymphocytes was more pronounced during secondary than during primary immune response.

[Role of cholera toxin-induced apoptosis in alteration of macrophages in mice].

AIM: To study the role of active programmed cell death induced by Vibrio cholerae antigens in alteration of peritoneal macrophages of experimental animals. MATERIALS AND METHODS: Apoptosis was assessed by cytofluorometric analysis with propidium iodide using cytofluorometer "Coulter" as well as on characteristic morphological changes of cells in stained histological preparations. RESULTS: Performed experiments carried out by both methods provide evidence that V. cholerae and its antigens (cholera toxin, neuraminidase, chitinase, and lypopolysaccharide) cause apoptosis of mice peritoneal macrophages, which leads to their alteration. CONCLUSION: Our results demonstrate that programmed cell death of phagocytes is one of the causes of cytotoxic effect of V.cholerae and its antigens. Performed experiments show the role of apoptosis of macrophages in formation of postimmunization immunosuppression after vaccination against cholera.

[Preparation of fractions and characteristic of neutrophilokines complex induced by Yersinia pestis EV].

Biochemical and immunobiologic characteristics of fractions of neutrophilokines during primary and secondary immune response against plague infection are presented. Fractions were obtained using gel chromatography from neutrophilokines complex induced by vaccine strain of Yersinia pestis. It was revealed that fractions of neutrophilokines regulate IL-2 synthesis by Th1-helpers, IL-4 and IL-5 synthesis by Th2-helpers and also expression of IL-2 receptors by immunocompetent cells. Helper effect of neutrophilokines' fractions was more pronounced during secondary immune response.

[Influence of neutrophilokines on the synthesis of lymphokines in the process of the formation of immunity to plague].

The evaluation of the complex of neutrophilokines whose synthesis was induced by Yersinia pestis vaccine strain EV on the production of lymphokines in the process of the formation of primary and secondary immunity to plague is presented. As revealed in this study, neutrophilokines regulate the synthesis of IL-2 by T helpers of type 1, IL-4 and IL-5 by T helpers of type 2, IL-1 by B lymphocytes, as well as the expression of receptors IL-2 by immunocompetent cells. The helper effect of neutrophilokines is more pronounced in the secondary immune response.

[Comparative evaluation of mono- and neutrophilokins inducing activity of Yersinia pestis antigens]. / Sravnitel'naia otsenka mono- i neitrofilokinindutsiruiushchei aktivnosti antigenov Yersinia pestis.

The results of the comparative analysis of the cytokine inducing activity of Yersinia pestis EV antigens are presented. Y. pestis fraction 1A (F1A) and lipopolysaccharide (LPS) were shown to induce mono- and neutrophilokines, regulating cooperative interaction of phagocytes in the process of immunity formation to plague. Neutrophilokines and monokines exceed in their capacity for inducing F1A such acknowledged inductor as Escherichia coli LPS. As revealed by the comparative evaluation of Y. pestis EV LPS and E. coli LPS, neutrophilokines synthesized under the action of the former preparation, have greater influence on the inhibition of the macrophage migration from the infection focus as well as on digestive activity of these cells (in secondary immune response) and on the labilization of the lysosome membranes of macrophages than neutrophilokines induced by E. coli LPS. At the same time they produce a lesser modulating effect on the killer and chemotactic activity of neutrophils, as well as on the expression of FC receptors (FcR) on their surface in comparison with monokines, synthesized under the influence of E. coli LPS.

[Monokine-producing activity of human monocyte-like cell line U937 induced by Yersinia pestis EV antigens]. / Monokinprodutsiruiushchaia aktivnost' monotsitopodobnoi linii kletok cheloveka U937, indutsirovannaia antigenami Yersinia pestis EV.

The data on a study of the monokine-producing ability of human monocyte-like cell line U937 are presented. Antigens of Yersinia pestis EV (lipopolysaccharide and fraction 1A) induce monokine production by cell line U937. The obtained monokines essentially enhance neutrophil killer and chemotactic activities, stimulate FcR expression, increase the number of lysosomes, and the lability of lysosomal membranes in neutrophils. F1A significantly suppresses LPS in respect to the ability to induce monokine production, which stimulate neutrophil functional activity.

[A method of assessing immunogenicity of preparations for plague prevention]. / Sposob opredeleniia immunogennosti preparatov dlia profilaktiki chumy.

A rapid, economic, and simple method for assessing the immunogenic properties of preparations for plague prevention is proposed. It is based on amplification of the bactericidal activity of peritoneal macrophages of experimental animals in the course of forming antiplague immunity. The increase in intracellular killing was assessed by the index of macrophage activation, which permits a tentative assessment of the immunogenic properties of the agent. This method is 6 times more rapid and requires 5 times less animals than routine methods and involves no manipulations with virulent strains of Yersinia pestis.

[The effect of a modification to the lipopolysaccharide of Yersinia pestis on its neutrophilokine-inducing activity]. / Vliianie modifikatsii lipopolisakharida chumnogo mikroba na neitrofilokin-indutsiruiushchuiu aktivnost'.

The ability of the isolated and modified Yersinia pestis LPS to induce the synthesis of the neutrophilokines that regulate the macrophage functional activity was studied. It is established that the Y. pestis LPS detoxication, especially by the method of deacylation, does not lead to the decrease in biological, in particular neutrophilokine-inducing activity of these preparations, but actually even increases it. These results are in agreement with many reports showing the possibility of decreasing the LPS toxicity without reducing immunostimulatory activity of this important component of the outer membrane of gram-negative bacteria.

[The virulence of Yersinia pestis strains in serial-passage in guinea pig peritoneal macrophages]. / Virulentnost' shtammov Yersinia pestis, proshedshikh kul'tivirovanie v peritoneal 'nykh makrofagakh morskikh svinok.

The cultivation of Y.pestis virulent strains in macrophages of guinea pigs has been found to enhance their virulence, decreased during storage, and to increase their antiphagocytic and cytopathic properties. This effect makes it expedient to recommend the passage of Y.pestis through peritoneal macrophages of guinea pigs with the aim of stabilizing their virulence. The proposed method reduces the duration of investigation 6 times, decreases the number of experimental animals used in the investigation and permits the simultaneous passage of a large number of subcultures.

[The effect of a vaccinal strain of the plague microbe on C3-receptor expression on the surfaces of peritoneal and alveolar macrophages]. / Vliianie vaktsinnogo shtamma chumnogo mikroba na ékspressiiu C3-retseptorov na poverkhnosti peritoneal'nykh i al'veoliarnykh makrofagov.

The work is devoted to the effect of vaccine strain of the plague microbe on the expression of C3-receptors (C3R) in interaction with macrophages in vitro and in vivo. It is established that the activation of macrophages accompanied by the increase of C3R expression on the external surface of the membrane of both peritoneal and alveolar macrophages occurs in the process of formation of antiplague immunity. Maximum activity of C3R in the both populations of macrophages is observed on the 7th day after vaccination. Immunization of the plague microbe by the vaccine strain does not change the character of response of peritoneal and alveolar macrophages to their interaction with this microorganism in vitro: a decrease of C3R expression on the surface of the both populations of cells obtained from both intact and immunized animals is observed. Heterogeneity of the studied populations as to C3R expression both in the intact and immune organism is detected.

[The effect of a vaccinal strain of Yersinia pestis on lysosome fusion with phagosomes in peritoneal and alveolar macrophages]. / Vliianie vaktsinnogo shtamma chumnogo mikroba na sliianie lizosom s fagosomami v peritoneal'nykh i al'veoliarnykh makrofagakh.

It is established that the frequency of phagosome-lysosome fusion in alveolar macrophages is lower than in the peritoneal cells upon endocytosis of Yersinia pestis. The subcutaneous immunization activates the phagosome-lysosome fusion in peritoneal macrophages, whereas alveolar cells remain without change. The aerogenic vaccination stimulates this process in both peritoneal and alveolar macrophages, as distinct from subcutaneous immunization.

[The use of the macrophage disappearance reaction for detecting delayed hypersensitivity to Yersinia pestis antigens]. / Ispol'zovanie reaktsii ischeznoveniia makrofagov dlia vyiavleniia povyshennoi chuvstvitel'nosti zamedlennogo tipa k antigenam Yersinia pestis.

The possibility of using the reaction of macrophage disappearance (RMD) for the detection of delayed hypersensitivity (DH) to Y. pestis has been studied. As the result of these studies, RMD has been found suitable, in principle, for use in the quantitative evaluation of DH to Y. pestis. High sensitivity and specificity of this reaction have been established. The presence of DH in the process of the formation of immunity after immunization with Y. pestis antigen FIA has been shown. RMD can be observed during 28 days after immunization (the term of observation).

[The expression of Fc gamma receptors on the surface of macrophages activated by a vaccinal strain of Yersinia pestis]. / Ekspressiia Fc gamma-retseptorov na poverkhnosti makrofagov, aktivirovannykh vaktsinnym shtammom chumnogo mikroba.

The expression of Fc gamma R on the surface of macrophages in the process of antiplague immunity formation is analyzed. The stud is performed on the alveolar and peritoneal macrophages obtained from intact and immunized guinea pigs in different periods after vaccination (the 1st, 7th, 14th and 21st day). It is established that during the formation of the antiplague immunity there occurs activation of macrophages which is accompanied by an increase of the Fc gamma R expression on the outer surface of the membrane both of peritoneal and alveolar macrophages and the pattern of response of these cells to the interaction with the vaccine strain of the plague microbe changes. The Fc gamma R expression heterogeneity of certain macrophage populations is revealed both in an intact and in immune organism as well as different pattern of the intact alveolar and peritoneal macrophage response during the interaction with the vaccine strain of the antiplague microbe. These differences are levelled in the process of the antiplague immunity formation.

[Changes in the "latent" virulence of a vaccinal strain of Yersinia pestis multiplying within macrophages]. / Izmenenie "latentnoi" virulentnosti vaktsinnogo shtamma Yersinia pestis pri razmnozhenii vnutri makrofagov.

The multiplication of Y. pestis vaccinal strain inside peritoneal macrophages of guinea pigs and white mice in vitro leads to an essential increase in its latent virulence. This effect is most pronounced when guinea pig macrophages are used. Changes in the latent virulence of Y. pestis vaccinal strains, occurring in the process of their passage inside macrophages in vitro, correlate with those observed in vivo, i.e. in animal experiments.