Results of immunological experiments aboard the Cosmos biosatellites and problems in space immunology
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Cosmos 1887 Project↗
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Basic and clinical immunology
Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.
Review↗
Methods for microbiological and immunological studies of space flight crews
Systematic laboratory procedures compiled as an outgrowth of a joint U.S./U.S.S.R. microbiological-immunological experiment performed during the Apollo-Soyuz Test Project space flight are presented. Included are mutually compatible methods for the identification of aerobic and microaerophilic bacteria, yeast and yeastlike microorganisms, and filamentous fungi; methods for the bacteriophage typing of Staphylococcus aureus; and methods for determining the sensitivity of S. aureus to antibiotics. Immunological methods using blood and immunological and biochemical methods using salivary parotid fluid are also described. Formulas for media and laboratory reagents used are listed.
Taylor, G. R.↗
Cosmos-1989 immunology studies
Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.
Sonnenfeld, Gerald↗
Immunology presentation at the 1990 NASA/NSF Antarctica Biomedical Science Working Group
An overview of methodology used for determining human in vitro lymphocyte activation, proliferation and effector cell function was presented and results of previous manned space flight immunology studies from Apollo through Shuttle were reviewed. Until the Shuttle era, lymphocyte assays were not very sensitive and had such large variations among normal subjects that it was difficult to define a consistent effect of space flight. More sensitive assay, however, even with Shuttle missions as brief as 6 days indicate depressed T-cell proliferative responses are routinely observed following space flight. Using a slight modification of the Shuttle assay, five different human stress-immunology models have been studied over the last 6 years in our lab. These have included: academic examinations of medical students having blood drawn during major test periods on three separate groups of first year students and two hypoxia studies (at 25,000 feet in a 6 week chamber ascent to the equivalent of Mount Everest and twice on Pikes Peak at 14,000 feet). These studies are particularly pertinent to Antarctica, since the altitude equivalent of 11,000 feet at the South Pole may affect some of the variables that are being measured in immunology, physiology or cognitive studies. An extravehicular study was performed drawing blood from 35 individuals before and immediately following a chamber exposure study. Preliminary results from 30 Shuttle astronauts investigated immunophenotype analysis and the role of a novel monocyte population in modulating the previously observed suppressed in vitro immune function. The results of the Air Force Academy cadet stress study were also presented.
Meehan, Richard T.↗
Immunological characterization of pulmonary intravascular macrophages
Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.
NASA Discipline Cell Biology↗
Mouse infection models for space flight immunology
Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.
Review↗
Hematology and immunology studies
The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.
Stephen L. Kimzey↗
Cosmos 2229 immunology study (Experiment K-8-07)
The purpose of the current study was to further validate use of the rhesus monkey as a model for humans in future space flight testing. The areas of immunological importance examined in the Cosmos 2229 flight were represented by two sets of studies. The first set of studies determined the effect of space flight on the ability of bone marrow cells to respond to granulocyte/monocyte colony stimulating factor (GM-CSF). GM-CSF is an important regulator in the differentiation of bone marrow cells of both monocyte/macrophage and granulocyte lineages and any change in the ability of these cells to respond to GM-CSF can result in altered immune function. A second set of studies determined space flight effects on the expression of cell surface markers on both spleen and bone marrow cells. Immune cell markers included in this study were those for T-cell, B-cell, natural killer cell, and interleukin-2 populations. Variations from a normal cell population percentage, as represented by these markers, can be correlated with alterations in immunological function. Cells were stained with fluorescein-labelled antibodies directed against the appropriate antigens, and then analyzed using a flow cytometer.
Sonnenfeld, Gerald↗
Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys
During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.
unmanned↗
The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations
This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.
Salyut Project↗
Overview of spaceflight immunology studies
The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.
NASA Discipline Number 18-10↗
Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight
Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and functional conditions of impacted cells/organisms. The administration of an experimental anti-radiation vaccine may provide an immunologically based, adjunct method of prevention or prophylaxis against clinical ARS. The administration of experimental anti-radiation serum (ARS) and the use of the blood dialysis methods, such as immune plasma-sorption, may assist in the clearance of radiation-specific toxins and may enhance established strategies for the mitigation of the biological effects leading to ARS, and should be evaluated for use on exploration-class space missions.
Popov, Dmitri↗
The effect of tetrathionate on the stability and immunological properties of muscle triosephosphate dehydrogenases
Tetrathionate effect on stability and immunological properties of muscle triosephosphate dehydrogenases
IMMUNOLOGY↗
Feasibility study for the manufacture of zero gravity pharmaceuticles, immunological, and viral agents
The feasibility of extracting, isolating, purifying, separating, or preparing medical and biological products of high socio-economic value in space was studied. In particular, the study was designed to concentrate on the isolation or purification of virals, pharmaceutical and immunological agents by means of electrophoresis, as the Apollo 16 flight demonstrated that a mixed population of latex spheres (.2 and .8 microns) could be successfully separated by electrophoresis in space and without sedimentation with minimal convection. This prompted NASA scientists to look into the possibility of carrying out types of biochemical experiments that would utilize space for medical purposes.
Source record↗
Evidence for two immunologically distinct acetyl-coenzyme A synthetases in yeast
Evidence is presented that clearly establishes the presence of two acetyl-CoA synthetases in Saccharomyces cerevisiae, one elaborated under 'aerobic' conditions, the other under 'nonaerobic' conditions. The antibody produced by each enzyme is immunologically specific.
Satyanarayana, T.↗
Hematology and immunology studies - The second manned Skylab mission
The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.
Kimzey, S. L.↗
Hematology and immunology studies
A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.
Kimzey, S. L.↗