[Immune status and resistance to the tick-borne encephalitis virus in directed exposure to particular links in immunogenesis]. / Immunnyi status i rezistentnost' k virusu kleshchevogo éntsefalita v usloviiakh napravlennogo vozdeistviia na opredelennye zven'ia immunogeneza.

Mechanism of specific resistance development in experimental tick-borne encephalitis (TBE) and possible effects on this mechanism were studied. Thorough characterization of the immune status of animals included quantitative and functional changes in populations of T and B lymphocytes determined over time via changes in the rosette-forming and antibody producing cells, antihemagglutinins, and index of migration inhibition. Stimulation or inhibition of some links of immunogenesis by means of preparations of directed effect (carageenan, ascorbic acid, heterologous serum, theophylline, levamisole) was reflected in parameters of the immune status and pathogenetic features of TBE. The appearance in the first days after infection of marked specific sensitization, high values of RFC in passive rosette-formation and inhibited function of antibody producing cells, no IgG synthesis by the end of the 1st week were accompanied by high lethality which indicated the lack of resistance to primary infection. The degree of specific sensitization and responsiveness of the animals to antigen was inversely, and antibody response directly related to the degree of resistance.

[Variants of the host immune response to the tick-borne encephalitis virus]. / Varianty immunnogo otveta khoziaina na virus kleshchevogo éntsefalita.

Syrian hamsters intracerebrally infected with tick-borne encephalitis (TBE) virus were used to study the correlation between virulence of the strains, their serotype, form and course of the disease, average survival time (AST) of hamsters, features of CNS pathomorphology, and the changes of values of cell-mediated and humoral immunity. Thirty one strains of TBE virus isolated in Siberia and Far East were studied. Virulence of the strains ranged from 100% to 5%, AST from 5 to 237 days. Hamsters developed acute lethal encephalitis, subacute encephalitis, or asymptomatic infection. Most virulent strains produced early and extensive lesions in the brain stem. In encephalitis with subacute course pathomorphological changes in the CNS developed slower and the brain stem was less involved. Each variant of TBE course was associated with a certain pattern of host immune response formed as early as the first day of infection. Highly virulent strains inducing acute encephalitis and 100% lethality within 5-9 days produced immune response characterized by high antigen reactivity of lymphocytes by the level of rosette-forming cells, marked specific sensitization in splenocyte migration-inhibition test, moderate antibody-producing cell reaction, increased thymus weight index, low values of nonspecific resistance with low levels of antihemagglutinins and virus-neutralizing antibody by the end of the first week. Different immunologic condition was associated with asymptomatic infection and increase of AST to 100-237 days.

[Interrelation of animal genotype and viral strain characteristics to the course of experimental tick-borne encephalitis]. / Vzaimosviaz' genotipa zhivotnogo i shtammovykh osobennostei virusa s techeniem éksperimental'nogo kleshchevogo éntsefalita.

Differences in the susceptibility to a single subcutaneous inoculation of tick-borne encephalitis (TBE) virus, features of immune response and development of resistance were studied in animals of one species but 2 genotypes (mouse lines CBA and C57BL). In the formation of resistance, the determining factors include the degree of susceptibility, specific sensitization of the animal to the definite antigen, and the level of specific microglobulins. No resistance is formed in C57BL mice highly sensitive to TBE virus antigen.

[Activating effect of cyclophosphane at late stages of persistence of the tick-borne encephalitis virus]. / Aktiviruiushchii éffekt tsiklofosfana na pozdnikh étapakh persistentsii virusa kleshchevogo éntsefalita.

Conditions of activation of persistent infection caused by subcutaneous inoculation of Syrian hamsters with the B-383 and Vasilchenko strains of tick-borne encephalitis virus (TBE) were studied. After 2 administrations of cyclophosphane (CP) on day 170 of infection clinically manifest disease developed in some animals with increasingly severe pathomorphological lesions in the CNS. Several variants of activated TBE virus were isolated from brains and spleens of CP-treated hamsters. The activation of persistent infection was observed in the presence of marked decreased of humoral immunity level, weight of the thymus, and values of spontaneous rosette-formation.

[Features of immunogenesis in simians infected with attenuated strains of tick-borne encephalitis and Langat virus]. / Kharakteristika immunogeneza u obez'ian, infitsirovannykh attenuirovannymi shtammami virusov kleshchevogo éntsefalita i Langat.

Certain parameters of humoral and cellular immunity induced by attenuated tick-borne encephalitis (TBE) and Langat virus strains were studied in monkeys. The immunogenic activity of the strains inoculated subcutaneously and intracerebrally was manifested by two processes: synthesis of specific antibody and cellular immune response. The highest titers of humoral immunity in N, HI, and CF tests were observed to homologous viruses. The immune response to both homologous and heterologous viruses could be optimized by increasing the number of antigenic stimulations. The sequence of antibody synthesis of the macro- and microglobulin series was similar in monkeys infected with virulent and attenuated strains. Cellular immunity reactions were detected and changes in the quantity and functional activity of T- and B-lymphocytes were determined. Most marked immunological changes were observed with the virulent TBE virus strain as compared with naturally and experimentally attenuated Langat virus strains.

[Functional activity of the macrophage elements of animal peritoneal exudate in the process of infection by tick-borne encephalitis complex viruses]. / Izuchenie funktsional'noi aktivnosti makrofagal'nykh élementov peritoneal'nogo ékssudata zhivotnykh v protsesse infitstirovaniia virusami kompleksa kleshchevogo éntsefalita.

Investigations of the functional activity values of macrophages showed that free peritoneal macrophages of random-bred mice and guinea pigs participated in primary immune response to a single subcutaneous inoculation of the Pan strain of tick-borne encephalitiss virus. TR-21 strain of Langat virus, and the 237 strain, an experimentally attenuated variant of the latter. When the mice developed an acute infection, functional changes of macrophages were characterized by increased phagocytic activity towards infected cells. In subacute infection in mice and inapparent infection in guinea pigs nonspecific resistance increased as manifested in activation of phagocytosis of non-infected cells and developing in the presence of immune response and specific sensitization of the animal hosts.

[Comparative study of B-lymphocyte activity in the spleen of mice infected with viruses of the tick-borne encephalitis complex]. / Sravnitel'noe izuchenie aktivnosti B-limfotsitov v selezenke myshei, infitsirovannykh virusami kompleksa kleshchevogo éntsefalita.

Most arbovirus infections are characterized by multiplication of the causative agent in tissues of the reticuloendothelial system. In this study, the effect of some viruses of the tick-borne encephalitis complex on the reaction of B-cells of mouse spleens was investigated by the hemolysin-producing activity (number of plaque-forming cells). To equal small doses of a highly virulent (Pan), naturally attenuated (Tp-21) and experimentally attenuated (Tp-21-237) strains the immunocompetent cells of mouse spleens responded by active reactions. The immunocompetence of these cells after primary introduction of the antigens persists and revaccination response occurs after a secondary infection with the same viruses. Under these experimental conditions the active response of spleen cells to the antigenic stimulation correlates with formation of the specific resistance and does not correlate with the level of antihemagglutinins in the blood.