[Outcome of the long-term isolation on the development of allergic reactions in humans]. / Vliianie dlitel'noi izoliatsii na formirovanie allergicheskikh reaktsii u cheloveka.

Studied were consequences of long-term isolation in airtight environment for development of the type-I (IgE-antibodies production) and type-IV (involvement of sensibilized T-lymphocytes) allergic reactions in humans. No significant changes in total IgE, specific IgE-antibodies for domestic, epidermal, fungal, grass pollen and food-borne allergens or serum IL-4 level were found in the period of the 240-d isolation with the microclimate and atmospheric parameters within their normal variations, and on completion of the experiment. Yet, after 3 mos. in isolation all subjects exhibited inhibited leukocyte migration in the presence of tuberculin. These findings bear witness to an activation of sensibilized lymphocytes known as effectors of delayed hypersensitivity.

[Effects of the spaceflight factors on the immune system]. / Vliianie faktorov kosmicheskogo poleta na immunitet.

The paper summarizes the main trends and milestones of space immunology starting with initial ground-based investigations with animals to recent experiments in piloted and automatic space vehicles data of which have been highlighted in numerous publications. There is a brief description of lines and results of investigations with participation of cosmonauts, and using laboratory animals and cell cultures. The author dwells upon the present-day notion of immune responses to extreme conditions and future topics of investigations.

Simulated microgravity, psychic stress, and immune cells in men: observations during 120-day 6 degrees HDT.

Because 6 degrees head-down tilt (HDT) is an established method to mimic low gravity on earth, the aim of the present study was to determine the effects of 120-day HDT on psychic stress and peripheral blood immune cells in six healthy male volunteers. Psychological state was assessed by a current stress test, and cortisol was measured in saliva. During HDT, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly altered. In addition, urine excretion of dopamine and norepinephrine increased. The innate part of the immune response was activated, as evidenced by the increase in the expression of beta(2)-integrins on polymorphonuclear leukocytes and a rise in the number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B lymphocytes were observed. Plasma levels of interleukin-6 increased significantly and returned to basal levels after the end of the HDT period. Thus 6 degrees HDT appears to be a valid model to induce psychic stress and neuroendocrine-related changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during long-duration spaceflights.

[Immunologic reactivity and status of the intestinal viral flora of humans in pressurized chambers]. / Immunologicheskaia reaktivnosti' i sostoianie kishechnoi virusnoi flory chekoveka pri obitanii v germetichno zamknutykh pomeshcheniiakh.

Immunity status and intestinal viral flora were studied in 5 experiments with long-term exposure of 26 male subjects in pressurized chamber. In two experiments with congenital microclimate and gaseous environment cellular and humoral indices of immunity did not deviate from the physiological norm. None of 14 subjects in these experiments was identified as a virus-carrier. In three experiments with hard environmental conditions (elevated concentrations of ammonia and carbon dioxide) viruses were isolated from 8 out of 12 subjects. Activation of viral flora mainly occurred on a background of impaired immunologic reactivity. In two experiments carriage of virus was asymptomatic; in the third experiment with the rise of ammonia up to 7 mg/m3 two subjects developed clinic signs that could have been engendered by enteric viruses, the Coxsackie B strain specifically.

[Tuberculin-dependent and nonspecific migration activity of leukocytes in astronauts]. / Tuberkulinzavisimaia i nespetsificheskaia migratsionnaia aktivnost' leikotsitov u kosmonavtov.

There have been presented the results of studying the reactivity of leucocytes with respect to tuberculin and monspecific migration activity of leukocytes in the cosmonatus pre flight and after completion of orbital expeditions of various duration are presented. In some cosmonauts tuberculin rearranged migration of leukocytes. This may bear witness to activisation of the immunity system in response to the antigens which had been already familiar to test-subjects. Experimental data pointed to significant changes in leukocyte mobility in 12 out of 28 cosmonauts examined on days 1 and 7-14 of recovery after the first or repeated long-duration space missions indicating some functional disorders in the phagocytic link which may lead to a typical decline in human resistance to infections.

[The diagnosis of disorders of the T-cell immunity component in space flight]. / Diagnostika narushenii T-kletochnogo zvena immuniteta v kosmicheskom polete.

The investigation yielded two modifications of the procedure FOR determination of T-lymphocytes' functional activity in microsamples of the finger capillary blood and PHA-assisted cultivation of cells in syringe for subsequent morphological analysis by cosmonauts in flight. Testing of the proposed modifications in 14 healthy donors with unconstrained work/rest schedule, 4 volunteers in 60- and 6 volunteers in 120-day HDT showed a rather high comparability of data obtained with the modified and genuine procedures for determination of the T-lymphocytes proliferative activity in cosmonauts before and after orbital flights. Thus, the modified procedures can be successfully used for monitoring the immune status of cosmonauts on missions, and individuals exposed to extreme environments.

[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.

[Carbohydrate adaptive substance for prophylaxis of immune disorders and correction of dysbacterioses]. / Uglevodnyi adaptogen dlia profilaktiki immunnykh rasstroistv i korrektsii disbakteriozov.

Effects of a new preparation, adaptokhit, on the intestinal microbiocenosis and some parameters of immune resistance were studied in Macaque rhesus during 13-day hypokinesia. Experimental animals were given adaptokhit as an alimentary supplement preventing dysbiotic consequences of the microecologic unbalance due to motor restraint. Results of the investigation showed certain distinctions in the intestinal microflora in the experimental and control animals as early as on day three of the experiment. Intestinal microflora of the experimental primates who daily consumed adaptokhit at 50 mg/kg of the body remained stable throughout the period of observation. In contrast, in their controls lactoflora was found to decrease in parallel to the growth of opportunistically pathogenic endobacteria including representatives of Proteus and Clostridia sp., and development of dysbacteriosis of categories II and III. Besides, in the experimental animals adaptokhit prevented decline in the proliferative activity of lymphocytes further into adaptation. Also, at the final stage of observation following canceling the preparation there were signs of normalization of the allergologic status of primates in the experimental group. Therefore, adaptokhit can be used as an alimentary supplement to strengthen the colony resistance of animals in extreme conditions.

[Lipid peroxidation and antioxidative system in imitation diving]. / Perekisnoe okislenie lipidov i sostoianie antiokislitel'noi sistemy pri imitatsionnom pogruzhenii.

Plasma lipid oxidation (LPO) and antioxidative system were examined in test divers who made imitation diving in the pressure chamber to the depth of 250 meters. Imitation diving showed higher iron levels, followed by a rise in the concentration of primary LPO products. There were no increases in the levels of secondary LPO products probably due to the fact that the ceruloplasmin-transferrin system released active iron from the reaction and that peroxy radicals were inactivated by SH groups.

[Human cellular immunity and space flights]. / Kletochnyi immunitet cheloveka i kosmicheskii polet.

Results of studying cellular immunity of crew members of long-term space missions, data of an experiment with extended head-down tilting of human subjects (HDT), and data obtained in the course of adapting immunologic test methods for the use in microgravity are summarized. Disorders in immunologic reactivity were shown to occur under the conditions of space flight. They included decreases in both quantitative and functional indices of cellular immunity, and emergence of signs of sensibilization to different allergens. The modified tests were evaluated by efficacy of determination of the proliferative activity of lymphocytes in minimal volumes of capillary blood inside one-piece syringes with a medium containing PHA and the Cytodex-1 suspension, evaluation of natural cytotoxicity on the level of an effector cell (number of peripheral blood lymphocytes capable of producing conjugates with fixed target cells). Sensibilization to allergens of normal human microflora was tested in analogs of routine hematocrit capillaries used for examination of healthy donors under ordinary rest-work regimen. No significant differences between the standard and modified tests were revealed. The proposed test modifications are quite simple in use and require minimum of equipment.

[Migration capacity of phagocytes during simulation of some spaceflight factors under the terrestrial conditions]. / Migratsionnaia sposobnost' fagotsitiruiushchikh kletok pri modelirovanii faktorov kosmicheskogo poleta v nazemnykh usloviiakh.

Migration activity of the leukocytes featuring the functional state and metabolic activity of immunocompetent cells was studied. Migration of phagocyting cells was explored in 8 female test-subjects in the course of 120-day head-down bed rest and 3 male volunteers isolated in a hermetically sealed room over a similar period. Bed rest without use of preventive measures decreased significantly the migration activity of leukocytes; on the opposite, administration of the preventive measures by the bedrested subjects doubled the parameter. In the experiment with the long-term isolation the activity of leukocytes decreased significantly.

Phagocyte system under spaceflight conditions.

The spaceflight conditions lead to disturbances in immune system and cause the changes in microbial and chemical environment that create preconditions for immunodeficiency and allergic disease development. With the spaceflights lengthening the problem of crewmembers immunodeficiency and the probability of allergic disease manifestation became actual. The higher risk of various pathological conditions noted in cosmonauts during space flight due to lowered immunological resistance and unnatural biological and chemical environment (autoimmune reactions, bacterial and viral autoinfections, possible allergic events etc.) proves the need of studying the mechanisms of these disturbances and determination the most labile links between the immune system and antigen environment. In this case phagocytes seems to be one of the most important cells that can influence both induction and effector stage of immune reactions and also take part in the regulation of the immune response. The goal of the investigation was to conduct studies of one of the of the phagocytes metabolic and migration activity that are closely connected with functional activity of the cells.

Immune responses in extreme environments.

In order to identify some of these interactions and regulation between the immune system and other physiological variables we have investigated the immune status in extreme conditions such as long term isolation and confinement, strict antiorthostatic bed rest and spaceflight.

[Immune resistance of humans during extended isolation]. / Immunologicheskaia rezistentnost' cheloveka pri dlitel'noi izoliatsii.

Analyzed were parameters of the immune reactivity and allergological status of participants in the 135-day chamber experiment with periods of induced psychoemotional strain. Stressful situations gave rise to shifts in the antibody system, i.e. decreased blood levels of ImgA, ImgM, and ImgG, decline in the functional activity of T-lymphocytes, suppression of the cytokinetic activity of lymphocytes-natural killers, and sensibilization to various allergens. Totality of these shifts resembles the ones which are typically seen during initial readaptation to the Earth's conditions on after long-term space mission.

Effect of SLS-2 spaceflight on immunologic parameters of rats.

During the Spacelab Life Sciences-2 mission, rats were dissected in space and biosamples were returned to Earth for analysis. Immunologic studies addressed the kinetics of T lymphocyte proliferative responses, cytotoxic activity of natural killer cells, and cytokine production. Experiments were performed by using spleen and bone marrow of rats dissected before flight, during flight, immediately after landing of the space shuttle (R + 0), or 14 days after landing (R + 14), as well as those of respective control animals. Each group consisted of five male Sprague-Dawley rats. It was demonstrated that T lymphocyte activity of rats dissected in flight was significantly decreased compared with the controls. This was observed during 48-, 72-, and 96-h cultivation and stimulation with the following mitogenic stimuli: concanavalin A (Con A; 0.1, 1.0, and 10.0 mg/ml), phytohemagglutinin (PHA; 2.5 mg/ml), and interleukin-2 (IL-2; 1 U/ml). The cell proliferation rate in rats dissected immediately after landing did not decrease, whereas that in rats dissected at R + 14 increased. The activity of spleen natural killer cells was reduced in response to 51Cr-labeled target cells during flight (YAC-1 and K-562) and after flight (YAC-1). At R + 14, their activity returned to normal. Another technique employed to measure natural cytotoxicity, using [3H]uridine-labeled target cells and ribonuclease, did not reveal any differences between control and experimental groups. In bone marrow, the activity of natural killer cells did not vary significantly. The production of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, and TNF-beta in spleen cell cultures of the flight rats was reduced. At R + 0, IL-1 and TNF-beta levels remained lowered, whereas TNF-alpha was increased. At R + 0, interferon-alpha and interferon-gamma levels were diminished. In summary, cell-mediated immunity in rats was significantly suppressed during flight. The time course variation of immune parameters after flight suggests that the changes may truly indicate a response of the immune system to spaceflight conditions that could increase over time.

Natural killer cells after ALTAIR mission.

Reduced in vitro NK cytotoxic activity have routinely been observed after both prolonged and short-term space flights. This study investigated the effects of space flight on NK cell functions, NK cell counts and the production of IL-2 and TNF by lymphocytes of French-Russian crew members. In the French cosmonaut, after 21 days space flight, the cytotoxic activity of NK cells, the capacity the NK cells to bind and lyse the individual target cells and the percentage of NK cells were decreased. In this cosmonaut a twofold reduction TNF production in cultures of lymphocytes stimulated with PMA and with the mixture of PHA and PMA was observed on the first day after landing. However, the activity of the production of TNF in 48-hour PHA-cultures of lymphocytes was unchanged and the biological activity of IL-2 was not reduced. The immunological examination did not detect any substantial deviations from the norm in both russian cosmonauts after 197 days space flight. Various explanations for decreased cytotoxicity in cosmonauts after space flight can be proposed, and these include the defective function of NK cells and reduced numbers of circulating effector cells.

The natural cytotoxicity in cosmonauts on board space stations.

The nature of the changes of resistance to infection seems to be very important. Our studies indicate that different functions of natural killers could be depressed after the spaceflight. The decrease of the percentage of the lymphocytes that can bind target cells lead to the lowering of the "active" NK level and this can be resulted in the depression of total NK activity and lowering of resistance to viral and tumor antigens. The investigation of natural killer cells in cosmonauts before and after short and long- term spaceflights also revealed the important role of spaceflight duration, stress and individual immune reactivity.

[Effects of space flight factors on production of oxygen radicals by phagocytes in cosmonauts]. / Vliianie faktorov kosmicheskogo poleta na produktsiiu kislorodnykh radikalov aktivirovannymi fagotsitami u kosmonautov.

In cosmonauts participated in space missions of various duration there changed one of the most important functions of phagocytes--the capacity to produce the active forms of oxygen during effect of corpuscular activator of zymosan. These changes depending on flight duration and individual peculiarities of cosmonauts manifested both as increase and decrease of the parameters studied. Family analysis of chemiluminescence of phagocytosing cells of the blood has revealed much importance of genotype in genesis of the variability of this function which points to the utility of an individual approach to evaluation of the immunity in cosmonauts.