[Endogenous regulatory peptides, interferons and cytokines as adaptogens in exposure of the body to adverse environmental factors]. / Endogennye reguliatornye peptidy, interferony i tsitokiny kak adaptogeny pri vozdeistvii na organizm neblagopriiatnykh faktorov vneshnei sredy.

The authors summarize data on the efficacy of various prefabricated recombinant interferons against virus, bacterial, and chlamydial infections, and in unfavorable environments. The spaceflight factors were shown to have a negative influence on natural killers in the human body providing the immunological resistance and defence not only from foreign microorganisms but also the body cells transformed because of a virus infection or malignancy. Entalferon awakes a particular interest for its convenience in extreme conditions, space flight included. It is still an open issue whether the interferon sensitivity of natural killers is compromised by space flight. This trend of investigation seems to be of paramount importance and promise in the context of enhancing the antiviral, antimicrobic and antineoplastic immunity of cosmonauts.

[The effect of recombinant tumor necrosis factor on antibody formation in mice immunized with a preparation of the outer membranes from Francisella tularensis]. / Vliianie rekombinantnogo faktora nekroza opukholi na antitelogenez u myshei, immunizirovannykh preparatom vneshnikh membran Francisella tularensis.

The influence of exogenic human recombinant tumor necrosis factor (TNF-alpha) on antibody production in mice immunized with the preparation of F.tularensis outer membranes (OM) was studied. TNF-alpha was injected into mice in doses of 0.001-10 I.U. before and simultaneously with the injection of the preparation of F.tularensis OM. The levels of tularemia antibodies, determined by ELISA techniques, and the number of antibody-producing cells (APC) were studied. The study revealed that recombinant TNF-alpha in the range of doses used in this investigation stimulated the formation of humoral immunity. The injection of TNF-alpha in a dose of 0.001 I.U. was found to produce the most pronounced effect on the level of tularemia antibodies and the number of antibody-producing cells. The use TNF-alpha as immunomodulator made it possible to decrease the dose of the preparation of F.tularensis OM introduced as immunogenic agent without essential changes in the number of splenic APC and in the level of tularemia antibodies.

[The activity of NK and K cells in mice vaccinated against plague]. / Izuchenie aktivnosti EK i K-kletok u myshei, vaktsinirovannykh protiv chumy.

The activity of NK and K cells in mice immunized against plague has been studied. This activity has been shown to depend on the dose of the vaccine and the time elapsed after immunization. The booster immunization of mice leads to an increase in the specific sensitization of lymphocytes, the antibody level and to an increase in the activity of killer cells. Changes in the cytotoxicity of NK cells on days 21-28 after primary and booster immunization are considered to occur not due to the action of Yersinia pestis themselves, but as the result of the immunological transformation induced by these microorganisms in the animals.

[Europium-labelled Staphylococcus aureus protein A as a reagent for determining specific antibodies]. / Belok A Staphylococcus aureus, mechennyi evropiem, kak reagent dlia opredeleniia spetsificheskikh antitel.

In this work the conditions of labeling protein A with europium ions were studied and the conjugates obtained in this study were compared with traditional peroxidase conjugates currently used in immunochemistry. The conjugates of protein A with Eu3+ chelate were obtained with the use of cyclic dianhydride of diethylenetriaminepentaacetic acid (DADETPA). Conjugation methods with the use of DADETPA was shown to permit obtaining high-quality conjugates with europium chelates. Europium-labeled protein A ensured the sensitivity of the determination of adsorbed IgG at a level of 2 ng/ml and the dynamic analytical range within 3-1,000 ng/ml, which essentially exceeded similar characteristics of peroxidase conjugates with protein A. Europium-labeled protein A was used for the detection of antibodies to Francisella tularensis in the sera of humans immunized against tularemia. The sensitivity of this assay exceeded that of the enzyme immunoassay 10- to 40-fold. A conclusion was made on the possibility of using europium labelled protein A for the determination of specific antibodies to F.tularensis. This preparation may be useful in the determination of specific antibodies in low-immune sera.

[The immunological efficacy of Francisella tularensis outer membranes for hamadryas baboons]. / Immunologicheskaia éffektivnost' vneshnikh membran Francisella tularensis dlia obez'ian-gamadril.

The protective properties of the preparation of F. tularensis outer membranes (OM), obtained from F. tularensis vaccine strain 15, were studied in experiments on hamadryas baboons challenged subcutaneously with F. tularensis virulent strain Schu (nonarctic subspecies). The subcutaneous immunization with the OM preparation prevented the development of clinically pronounced infection in more than 70% of the monkeys challenged with F. tularensis strain Schu in a dose of 787 live microbial cells 30 days after immunization. Antibody titers determined in the immunized monkeys with the use of the agglutination test (AT) and the passive hemagglutination test (PHAT) were usual in minimal diagnostic limits (1:80 for AT and 1:320 for PHAT) and did not significantly rise by day 20 after immunization. In all intact animals infected with F. tularensis strain Schu the development of the infectious process was registered, which was accompanied by a rise in temperature exceeding 39.5 degrees C and a rise in the titer of specific antibodies.

[The activity of NK and K cells in people vaccinated and revaccinated against plague]. / Izuchenie aktivnosti EK i K-kletok u liudei, vaktsinirovannykh i revaktsinirovannykh protiv chumy.

Changes in the activity of NK and K cells in persons immunized against plague have been studied. A decrease in the activity of natural killer cells has been shown to occur. Booster immunization leads to a greater increase in the specific sensitization of lymphocytes, as well as in the antibody level. The observed increase of the activity of killer cells is regarded not as the result of the direct action of live Yersinia pestis cells, but as the result of the immunological changes in the body which they produce.

[The activity of natural killers and K cells and their interferon sensitivity in subjects inoculated against diphtheria and meningococcal infection]. / Izuchenie aktivnosti estestvennykh killerov, K-kletok, ikh chuvstvitel'nosti k interferonu u liudei, privitykh protiv difteriinoi i meningokokkovoi infektsii.

The work deals with the time course of changes in the activity of natural killers, K-cells, their sensitivity to interferon, which reflects, in our opinion, the reserve possibilities of this killer system simultaneously with the development of the specific sensitization of lymphocytes. Significant changes in the cytotoxicity of natural killers, K-cells, have been detected in persons immunized against meningococcal infection, especially in those immunized with meningococcal vaccine introduced in combination with diphtheria toxoid. In this latter group of volunteers even more pronounced sensitization of peripheral blood lymphocytes has been observed than in persons immunized with monopreparations. The results obtained in this investigation indicate that the determination of these cell reactions may be of importance in the evaluation of the effectiveness of immunization.

[The opsonizing activity of the sera of hamadryas baboons immunized with a preparation of the outer membranes of Francisella tularensis (based on data from the luminol-dependent luminescence method)]. / Opsoniziruiushchaia aktivnost' syvorotok obez'ian gamadrilov, immunizirovannykh preparatom vneshnikh membran Francisella tularensis (po dannym metoda liuminolzavisimoi khemiliuminestsentsii).

The opsonizing properties of sera obtained from hamadryas baboons immunized with the preparation of F. tularensis outer membranes (OM) were studied with the use of luminol-dependent chemiluminescence (CL) of whole blood. The immunization of monkeys with the OM preparation was shown to lead to the formation of functionally active antibodies possessing opsonizing properties with respect to virulent F. tularensis. Immune sera obtained from the animals immunized with live vaccine and from those immunized with OM preparation had no essential differences in their opsonizing properties. The level of IgG antibodies in immune sera correlated with the CL parameters of whole blood in the presence of F. tularensis opsonized with these sera. Increased CL of phagocytes observed after addition of bacteria and immune sera under test to whole blood taken from a nonimmune donor made it possible to evaluate the functional activity of antibodies, thus permitting its use as a test for the evaluation of the effectiveness of new vaccine preparations.

[The characteristics of the antibody response of animals immunized with components of the surface structures of Francisella tularensis]. / Osobennosti antitel'nogo otveta u zhivotnykh, immunizirovannykh komponentami poverkhnostnykh struktur Francisella tularensis]

Antibody formation in animals immunized with one of the components of F. tularensis surface structures was studied. The time course of antibody formation in 20 hamadryas baboons was studied in the passive hemagglutination (PHA) test, microagglutination (MA) test, and indirect enzyme immunoassay, used for the determination of IgG, IgA and IgM antibodies. The character of antibody response in the animals immunized with components of F. tularensis surface structures (S-complex) and with live tularemia vaccine was compared. The study revealed that immunization with the S-complex induced the formation of antibodies detected by all three methods. Antibody formation to the S-complex was found to be dose-dependent. With the increase of the injected dose of the S-complex, antibody titers determined in the PHA test decreased and those determined in the MA test increased, which was seemingly due to the induction of antibodies differing in their isotypes. After immunization with the S-complex the levels of IgG antibodies were lower and the levels of IgM antibodies by day 28 after immunization higher than after the injection of live tularemia vaccine.

[The use of microdot immunoenzyme analysis with visual detection for the determination of tularemia antibodies]. / Ispol'zovanie mikrotochechnogo immunofermentnogo analiza s vizual'noi indikatsiei dlia opredeleniia tuliaremiinykh antitel.

The possibility of using the micropoint enzyme immunoassay (EIA) on a nitrocellulose membrane with the visual evaluation of results for the detection of tularemia IgG antibodies in hamadryas baboons at the postvaccinal period has been studied. The sensitivity of this assay has been compared with that of the passive hemagglutination (PHA) test, the microagglutination (MA) test and EIA with the spectrophotometric evaluation of results in plates. As shown in this study, EIA in the above-mentioned modification can be successfully used for the detection of tularemia antibodies in the blood serum. The sensitivity of micropoint EIA has proved to be not inferior to that of EIA in plates, while exceeding the sensitivity of the PHA test 10- to 20-fold and the sensitivity of the MA test 10- to 1,000-fold. This method is simple, reliable, highly sensitive, economic and requires no special equipment, which makes it highly promising for the diagnosis of tularemia and the evaluation of humoral immunity at the postvaccinal period.

[The efficacy of immunoenzyme assay in determining IgG in blood]. / Effektivnost' immunofermentnogo analiza dlia opredeleniia IgG v syvorotke krovi.

The efficacies of two methods for measuring human blood serum IgG, heterogenic enzyme immunoassay (EIA) and radial immunodiffusion in gel (RIG), are compared. The accuracy of both the methods was verified by the data of IgG spectrophotometry; IgG were isolated by ion exchange chromatography from human blood serum. The results of all the three methods were in high correlation: correlation coefficient of spectrophotometry and EIA data was 0.992, p less than 0.01; that of spectrophotometry and RIG data 0.975, p less than 0.01; that of RIG and EIA 0.888, p less than 0.01. Since EIA has some advantages over RIG (it is more rapid, sensitive, accurate, and the investigation may be automated), it is recommended for measuring human blood serum IgG in mass screenings.

[Suppressive action of bone marrow and spleen cells on antibody genesis and lymphoid cell proliferation in an in vitro culture of autoimmune mice (NZB.NZW)F1]. / Supressivnoe deistvie kletok kostnogo mozga i selezenki na antitelogenez i proliferatsiiu limfoidnykh kletok v kul'ture in vitro u autoimmunnykh myshei (NZB.NZW)F1.

The ability of bone marrow and spleen cells of autoimmune (NZB.NZW) F1 strain of mice of various age to suppress the immune response and spleen cells proliferation of young syngeneic mice in vitro was studied. The SRBC were used as an antigen. The proliferation rate was measured by the intensiveness of 3H-thymidine incorporation into DNA of cells being in the process of division. It has been found out that the bone marrow supressive activity in (NZB.NZW) F1 strain of mice undergoes age-associated changes. In mice 4-5 months of age the temporary reduction of suppressor-cell activity in the bone marrow is observed. The bone marrow suppressive activity recovers by 8-10 months, reaching the level of that observed in mice 1.5-2 months of age. In the spleens of (NZB.NZW) F1 strain of 8-10 months old mice suppressor cells appear lacking in young animals. The possibility of bone marrow B-suppressor participation in the development of the autoimmune process in (NZB.NZW) F1 strain of mice is discussed.

[Hematopoietic stem cell migration and differentiation in autoimmune mice of varying ages]. / Migratsiia i differentsirovka krovetvornykh stvolovykh kletok u autoimmunnykh myshei raznogo vozrasta.

Age-dependent migration and differentiation of hematopoietic stem cells was studied in autoimmune mice (NZB chi chi NZW) F(1) of different age. It was shown that the migration rate of stem cells in old (NZB X NZW) F(1) mice decreases. Despite the age the granulopoietic differentia of stem cells was inhibited in these mice. It is suggested that (NZB x NZW) F(1) mice have either an impaired development of T lymphocyte subpopulation affecting the granulopoietic differentiation of stem cells or a genetic defect of the granulopoietic progenitors (CFU(c)).