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All sourcesNASA NTRSDOE OSTI
NASA NTRS2009

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

Goodwin, T. J.↗
NASA NTRS2009

The Human in Space: Lesson from ISS

This viewgraph presentation reviews the lessons learned from manned space flight on the International Space Station. The contents include: 1) Overview of space flight effects on crewmembers; 2) General overview of immune system; 3) How does space flight alter immune system? 4) What factors associated with space flight inteact with crewmember immune function and impact health risks? 5) What is the current understanding of space flight effects on the immune system? and 6) Why should NASA be interested in immunology? Why is it significant?

Sams, Clarence F.↗
NASA NTRS2014

NASA HRP Immunology Discipline - Use of Terrestrial Analogs

Due to the cost and operational constraints, as well as technical implementation limitations, it is desirous to perform relevant space physiology investigations first in terrestrial 'space analogs'. This is particularly true for initial investigations, which may then provide appropriate focus for subsequent flight investigations, or for mechanistic investigations that simply cannot be performed during spaceflight. Appropriate analog choice is extremely important. There are a wide variety of terrestrial space analogs, each relevant to a particular physiological discipline (or disciplines) and each with a particular fidelity (or lack thereof) to spaceflight, and each with unique operational constraints. The HRP Immunology Discipline is tasked with managing the HRP Risk concerning clinical risk for Astronaut crews related to spaceflight-associated immune dysregulation. Such dysregulation has been documented to occur during spaceflight, and found to persist for the duration of a 6-month ISS mission. Studies continue to characterize the onorbit phenomenon, but it generally consists of diminished immunocyte function, dysregulated cytokine profiles, and persistent herpesvirus reactivation. Causes are thought to synergistically include microgravity, psychological or physiological stress, radiation, and/or circadian misalignment. An appropriate terrestrial analog for immune dysregulation would replicate as many of these influences as possible. Such analogs may include clinostat or bioreactor cell culture (microgravity), hindlimb suspension (stress, fluid shifts, hypokinesis), or human deployment to remote or extreme environments (isolation, stress, circadian). Also, the laboratory setting may be used as an analog, or to augment analogs, such as sleep deprivation/misalignment or human centrifugation to replicate gravitational stress. As an appropriate example of a NASA Disciplines use of Terrestrial space analogs, this talk will discuss spaceflight associated immune dysregulation, terrestrial immune analogs, and recent analog investigations.

Crucian, Brian↗
NASA NTRS2014

Probiotics in the Space Food System: Delivery, Microgravity Effects, and the Potential Benefit to Crew Health

As mission distance and duration increase, the need grows for non‐invasive disease prevention and immunomodulation, especially given the limited medical response capability expected for these missions and the immune dysregulation documented in crew. Additionally, changes in diet, lifestyle, antibiotic usage, and the environmental stresses during spaceflight may alter crewmembers' intestinal microbiome. The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers, with the potential to counteract the immune dysregulation that has been documented in spaceflight. Based on previous studies that demonstrated unique microbiological responses to the low shear environment of spaceflight, probiotic organisms hold the potential to induce enhanced beneficial responses through mechanisms, such as beneficial interactions with human immune cells and repression of colonization of pathogens on the mucosa. The work presented here will begin to address two research gaps related to providing probiotics in spaceflight: 1) delivery, and 2) the effect of the low shear microgravity environment on probiotic attributes. The probiotic Lactobacillus acidophilus was selected for investigation due to its wide commercial use and documented benefits that include inhibition of virulence related gene expression in pathogens and mucosal stimulation of immune cells. The delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. In order to demonstrate the potential of the space food system to deliver viable probiotic bacteria to crewmembers, the probiotic L. acidophilus was packaged in high barrier flight packaging in nonfat dry milk (NFDM) or retained in commercial capsule form. Viable cells were enumerated over 8 months of storage at 22, 4, and ‐80ºC. The survival of L. acidophilus rehydrated in NFDM, in a PBS control, and directly from the capsule was also evaluated following stress challenge with simulated gastric and intestinal juices to determine the method that would deliver the most viable cells to the intestine, where they would be expected to confer beneficial effects. L. acidophilus was found to be stable to gastric and intestinal juice challenge when delivered in rehydrated NFDM, even after two hours of exposure. In comparison, L. acidophilus was reduced by 1‐5 logs when exposed to gastric and intestinal juice directly and when rehydrated in a PBS control. Shelf life data indicated that L. acidophilus would require refrigerated or frozen storage to remain viable at adequate levels over the multi‐year storage periods required for spaceflight. This study suggests that the protective effect provided by the dairy matrix, and not merely rehydration prior to consumption, extends probiotic viability and stress tolerance during storage in spaceflight and in simulated digestion conditions more adequately than a capsule. In addition to effective delivery, it is essential to understand the microgravity effects on the stress tolerances and genetic expression of probiotic bacteria to enable optimization of growth, survival, strain selection, and conferred benefits in spaceflight. In our current study, ground‐based characterization of the growth, stress response, and transcriptomic response of L. acidophilus will be accomplished using the low shear modeled microgravity (LSMMG) culture environment in the rotating wall vessel (RWV). We hypothesize that L. acidophilus will maintain or improve its growth and stress response following culture in the LSMMG environment, and that transcriptomic analysis will define the associated molecular mechanism(s), resulting in the ability to optimize strain selection.

Castro, S. L.↗
NASA NTRS2018

Neutrophil to Lymphocyte Ratio: A Prognostic Indicator for Astronaut Health

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count data collected from astronauts and rodents that have flown for short- and long-term missions on board the International Space Station (ISS) was repurposed to determine the NLR pre-, in-, and post-flight. The results displayed that the NLR progressively increased during spaceflight in both human and mice, while a spike in the NLR was observed at post-flight landing, suggesting stress-induced factors may be involved. In addition, the ground-based chronic microgravity analog, hindlimb unloading in mice, indicated an increased NLR, along with induced myeloperoxidase expression, as measured by quantitative (q)PCR. The mechanism for increased NLR was further assessed in vitro using the NASA-developed rotating wall vessel (RWV) cell culture suspension system with human WBCs. The results indicated that simulated microgravity led to increased mature PMN counts, NLR profiles, and production of reactive oxygen species (ROS). Collectively, these studies show that an increased NLR is observed in spaceflight missions, and in chronic microgravity-analog simulation in mice, and that this effect may be potentiated by the oxidative stress response in blood cells under microgravity conditions. Furthermore, these results suggest that a disrupted NLR profile in spaceflight may further disrupt immune homeostasis, potentially causing chronic immune-mediated inflammatory diseases. Thus, we propose that the health status of astronauts during short- and long-term space missions can be monitored by their NLR profile, in addition to utilizing this measurement as a tool for interventions and countermeasure development to restore homeostatic immunity.

biomarker↗
NASA NTRS2019

Modeled Microgravity Induces Neutrophil Extracellular Trap (NET)osis Formation and Reduced Phagocytosis of Polymorphonuclear Neutrophils

Spaceflight can dysregulate immunity, by way of increasing granulocytes numbers with impaired function. Polymorphonuclear neutrophils (PMN) are granulocytes that are first responders to infection or injury, and consist of the largest pool of immune cells in humans. PMNs function during innate immunity, through phagocytosis and promotion of inflammation, via the release of reactive oxygen species (ROS) mediators and granule-containing enzymes, such as myeloperoxidase (MPO) and NADPH oxidase-2 (NOX-2). In addition, neutrophil extracellular trap (NET) formation is another mechanism of PMN surveillance that works independently of engulfment phagocytosis, and is a last resort function that can induce NETosis or PMN-specific cell death. Previous studies in our lab have identified increased mature neutrophils, ROS and MPO production, and reduced phagocytosis in granulocytes in simulated microgravity (sug) models of hindlimb unloading (HU) in adult mice and leukocytes cultured in high-aspect rotating wall vessels (HARV-RWV). Since sug impaired phagocytosis, but improved enzymatic mediator production of MPO and redox molecules, we sought to address the third known function of PMNs, NETosis. For this, PMNs were culture in the presence or absence of the anti-oxidant N-acetyl cysteine (NAC), which rescued impaired phagocytosis that was present in sug without NAC treatment. Further, NETosis was induced in sug that was no different in the presence of NAC, suggesting NAC targets independent functions of PMNs under sug. Collectively, these results suggest modeled microgravity induced NETosis, which opens a new avenue for spaceflight studies in immune dysfunction.

Paul, Amber M.↗
NASA NTRSDate not supplied

Hazards of Lunar Surface Exploration: Determining the Immunogenicity/Allergenicity of Lunar Dust

Although infrequent, there have been Apollo program reports of lunar dust (LD) exposure leading to notable upper respiratory symptoms in select crewmembers. Possible mechanisms include particulate irritation, oxidization and release of noxious gas, or legitimate adaptive immune-mediated response. Although sterile non-protein matter would not be expected to be an allergen, one Apollo flight surgeon reported increasing symptoms upon repeated exposure with associated eosinophilia, indicative of allergy (*Acta Astronautica. 2008 63 (7–10): 980–987). Many ISS crews display a pattern of persistent immune system dysregulation and latent virus reactivation (NPJ Microgravity. 2015 Sep 3; 1:15013; NPJ Microgravity. 2017 Apr 12; 3:11). Some ISS crews manifest atypical respiratory and/or dermatitis symptoms which could have an allergic pathogenesis (J Allergy Clin. Immunol. Pract. 2016 Jul-Aug; 4(4):759-762.e8). It is logical to anticipate crew immune dysregulation would worsen during prolonged deep space missions. Planetary surface hazards will only complicate crew health risks. This study with investigate if LD exposure will elicit an IgE mediated allergic response either to the LD itself or concomitant antigen exposure during spaceflight. Allergic reactivity could adversely increase clinical and operational impacts for long-duration lunar astronauts and affect countermeasure requirements for surface vehicles. Specific aims for this study are to answer two questions: (1) Does in vitro LD exposure result in increased histamine from human peripheral blood basophils? (2) Can LD impact the capacity of CD4+ T helper and/or CD19+ B-cell mediated IgE production? To address these questions, after the proposal and selection by NASA, our laboratory has separately requested and been approved for receipt of actual LD samples from the Apollo 16 mission. These samples will be used during the study to complete the proposed set of in vitro cell culture experiments (short and long term), using human peripheral blood mononuclear cells (PBMC) and basophils from both atopic and non-atopic individuals. Cells will be co-cultured with cellular mitogens, common recall antigens (Der p1), fine ground silica quartz (as a possible allergenic component of LD), or LD, to study whether LD exposure for varying time intervals will alter the generation of selective immune responses associated with clinical allergic reactions. Measured outputs include supernatant-derived IgE, tryptase, histamine, and selected cytokine levels. Cellular activation will be monitored by assessing activation markers via flow cytometry. EM/x-ray analysis will be used to determine cellular interactions with dust particles. A series of validation experiments was initiated in FY22 once the delivery of LD was received. Based on initial experimental findings, we are optimizing the culture conditions, LD concentrations, and refining our other protocol stimuli.

Audrie A. Colorado↗
NASA NTRSDate not supplied

Hazards of Lunar Surface Exploration: Determining the Immunogenicity/Allergenicity of Lunar Dust

Although infrequent, there have been Apollo program reports of lunar dust (LD) exposure leading to notable upper respiratory symptoms in select crewmembers. Possible mechanisms include particulate irritation, oxidization and release of noxious gas, or legitimate adaptive immune-mediated response. Although sterile non-protein matter would not be expected to be an allergen, one Apollo flight surgeon reported increasing symptoms upon repeated exposure with associated eosinophilia, indicative of allergy (*Acta Astronautica. 2008 63 (7–10): 980–987). Many ISS crews display a pattern of persistent immune system dysregulation and latent virus reactivation (NPJ Microgravity. 2015 Sep 3; 1:15013; NPJ Microgravity. 2017 Apr 12; 3:11). Some ISS crews manifest atypical respiratory and/or dermatitis symptoms which could have an allergic pathogenesis (J Allergy Clin. Immunol. Pract. 2016 Jul-Aug; 4(4):759-762.e8). It is logical to anticipate crew immune dysregulation would worsen during prolonged deep space missions. Planetary surface hazards will only complicate crew health risks. This study with investigate if LD exposure will elicit an IgE mediated allergic response either to the LD itself or concomitant antigen exposure during spaceflight. Allergic reactivity could adversely increase clinical and operational impacts for long-duration lunar astronauts and affect countermeasure requirements for surface vehicles. Specific aims for this study are to answer two questions: (1) Does in vitro LD exposure result in increased histamine from human peripheral blood basophils? (2) Can LD impact the capacity of CD4+ T helper and/or CD19+ B-cell mediated IgE production? To address these questions, after the proposal and selection by NASA, our laboratory has separately requested and been approved for receipt of actual LD samples from the Apollo 16 mission. These samples will be used during the study to complete the proposed set of in vitro cell culture experiments (short and long term), using human peripheral blood mononuclear cells (PBMC) and basophils from both atopic and non-atopic individuals. Cells will be co-cultured with cellular mitogens, common recall antigens (Der p1), fine ground silica quartz (as a possible allergenic component of LD), or LD, to study whether LD exposure for varying time intervals will alter the generation of selective immune responses associated with clinical allergic reactions. Measured outputs include supernatant-derived IgE, tryptase, histamine, and selected cytokine levels. Cellular activation will be monitored by assessing activation markers via flow cytometry. EM/x-ray analysis will be used to determine cellular interactions with dust particles. A series of validation experiments was initiated in FY22 once the delivery of LD was received. Based on initial experimental findings, we are optimizing the culture conditions, LD concentrations, and refining our other protocol stimuli.

immunology↗
NASA NTRS2023

T-Cell Shenanigans: The Impact of MHC Pathway & Lipid Metabolism Genes on T-Cell Differentiation in the Thymus

Astronaut health and proper immune function are key to the success and sustainability of long term missions in space. While previous studies have observed adaptive immune dysfunction such as diminished WBC counts and cytokine production during spaceflight, the underlying mechanisms behind why immune function worsens are poorly understood. Using transcriptomic data analyzed from mouse thymus tissues available from the GLDS-421 experiment on the Rodent Research-9 mission, we used the GeneLab standardized RNA-Seq pipeline and identified four genes that were largely dysregulated (p<0.05): lipid metabolic genes Hpgd and Pgr and cell cycle regulator genes Cenpe and Kif11. We analyzed how these genes regulate the MHC-TCR interaction, and used this understanding to propose a novel mechanism for alterations to T-cell differentiation. In our experimental methodology, we propose to use 36 transgenic CD4-CD8 mice and 12 wild-type mice from the Jackson Lab to create a microgravity-simulating hindlimb unloading model and test our hypothesis. By silencing the aforementioned genes using custom siRNA based primers, we will use flow cytometry and RNA-Seq to quantify Treg counts in comparison to naive CD4+ cells, Alamar Blue assay for observing the metabolic activity in T-cells, and Enzyme-Linked Immunosorbent Assay (ELISA) to observe the general immune response in terms of T-cell differentiation. We hope this methodology will improve our knowledge of MHC-TCR interaction, contribute to a better understanding of the mechanisms of autoimmune diseases such as lupus, and improve the success rate of newer cancer treatments such as CAR-T cell therapy.

GL4HS↗
NASA NTRSDate not supplied

Validation of Multisystem Countermeasures Protocol for Spaceflight during Antarctica Winter-over at Palmer Station (Palmer Countermeasures)

Stressors associated with spaceflight induce persistent immune compromise in astronauts which increase subclinical latent virus reactivation. In select crews, adverse clinical events have been documented. Antarctica winter-over (AWO) mission most closely reproduces these mission stressors: prolonged deployment, extreme environment, circadian misalignment, isolation, station lifestyle, and personal risk. The US maintains three primary stations in Antarctica: South Pole Station, McMurdo, and Palmer. Previous studies suggest that stations located near the interior of Antarctica (South Pole, McMurdo) have confounding effects on the immune system due to persistent hypobaric hypoxia. We hypothesized that winter-over at a coastal station (Palmer) would be more akin to spaceflight due to its normoxic but still extreme environment. Therefore, AWO at Palmer Station was selected, and validated in a pilot study [2], as the platform for testing and validating the effectiveness of an immune-restorative countermeasure protocol designed for deep space missions. Specifics include diet modifications, nutritional supplementation (vitamin D, probiotic, etc.), prescribed aerobic and resistive exercise, and a protocol of stress relieving virtual reality exercises. A multitude of biological sample types, including blood, saliva, and hair will be collected in tandem with the countermeasures in order to examine the combined effectiveness of the countermeasures. Samples and logs from subjects will be transported from Palmer Station to Johnson Space Center for further processing and distribution to co-investigators at the end of each winter-over. Extracted samples will be analyzed by appropriate testing platforms (Multiplex, qPCR, ELISA, etc.) to monitor alterations in leukocyte distribution, T cell and NK function, cytokine profiles, reactivation of latent herpesviruses, and nutritional factors. The data collected will be compared to a control year in which no countermeasures were deployed to evaluate the overall effectiveness of the analog and to validate the candidate immune countermeasure strategy. AWO 2023 concluded with the 4th in-mission timepoint conducted in September 2023. Samples for 16 subjects, including blood, saliva, hair, surveys, and PCR data, were all successfully returned from Antarctica to NASA/JSC mid-November 2023. Samples have since been distributed to co-investigators for further processing and analysis. With the completion of the first countermeasure year, preliminary data on the effectiveness of the deep-space protocol is being evaluated, however, no conclusions can be drawn yet until the completion of the second AWO countermeasure year, AWO 2024. AWO 2024 commenced in late-March 2024, with 13 subjects consenting and performing their baseline data collections (BDCs). Unique to the 2024 deployment, NSF lifted certain COVID restrictions and rallied the crewmembers in Punta Arenas, Chile. All NSF activities were transferred to this location and NASA was allowed, for the first time, to perform consent briefings, baseline samplings and training in person. This augment greatly increased the likelihood of success for the overwinter activities.

Cody L Gutierrez↗
NASA NTRSDate not supplied

Validation of Multisystem Countermeasures Protocol for Spaceflight during Antarctica Winter-over at Palmer Station (Palmer Countermeasures)

Stressors associated with spaceflight induce persistent immune compromise in astronauts which increase subclinical latent virus reactivation. In select crews, adverse clinical events have been documented. Antarctica winter-over (AWO) mission most closely reproduces these mission stressors: prolonged deployment, extreme environment, circadian misalignment, isolation, station lifestyle, and personal risk. The US maintains three primary stations in Antarctica: South Pole Station, McMurdo, and Palmer. Previous studies suggest that stations located near the interior of Antarctica (South Pole, McMurdo) have confounding effects on the immune system due to persistent hypobaric hypoxia. We hypothesized that winter-over at a coastal station (Palmer) would be more akin to spaceflight due to its normoxic but still extreme environment. Therefore, AWO at Palmer Station was selected, and validated in a pilot study, as the platform for testing and validating the effectiveness of an immune-restorative countermeasure protocol designed for deep space missions. Specifics include diet modifications, nutritional supplementation (vitamin D, probiotic, etc.), prescribed aerobic and resistive exercise, and a protocol of stress relieving virtual reality exercises. A multitude of biological sample types, including blood, saliva, and hair will be collected in tandem with the countermeasures in order to examine the combined effectiveness of the countermeasures. Samples and logs from subjects will be transported from Palmer Station to Johnson Space Center for further processing and distribution to co-investigators at the end of each winter-over. Extracted samples will be analyzed by appropriate testing platforms (Multiplex, qPCR, ELISA, etc.) to monitor alterations in leukocyte distribution, T cell and NK function, cytokine profiles, reactivation of latent herpesviruses, and nutritional factors. The data collected will be compared to a control year in which no countermeasures were deployed to evaluate the overall effectiveness of the analog and to validate the candidate immune countermeasure strategy. AWO 2023 concluded with the 4th in-mission timepoint conducted in September 2023. Samples for 16 subjects, including blood, saliva, hair, surveys, and PCR data, were all successfully returned from Antarctica to NASA/JSC mid-November 2023. Samples have since been distributed to co-investigators for further processing and analysis. With the completion of the first countermeasure year, preliminary data on the effectiveness of the deep-space protocol is being evaluated, however, no conclusions can be drawn yet until the completion of the second AWO countermeasure year, AWO 2024. AWO 2024 commenced in late-March 2024, with 13 subjects consenting and performing their baseline data collections (BDCs). Unique to the 2024 deployment, NSF lifted certain COVID restrictions and rallied the crewmembers in Punta Arenas, Chile. All NSF activities were transferred to this location and NASA was allowed, for the first time, to perform consent briefings, baseline samplings and training in person. This augment greatly increased the likelihood of success for the overwinter activities.

Cody L Gutierrez↗
NASA NTRS1999

Combined effects of space flight factors and radiation on humans

The probability that a dose of ionizing radiation kills a cell is about 10,000 times the probability that the cell will be transformed to malignancy. On the other hand, the number of cells killed required to significantly impact health is about 10,000 times the number that must be transformed to cause a late malignancy. If these two risks, cell killing and malignant transformation, are about equal, then the risk that occurs during a mission is more significant than the risk that occurs after a mission. The latent period for acute irradiation effects (cell killing) is about 2-4 weeks; the latent period for malignancy is 10-20 years. If these statements are approximately true, then the impact of cell killing on health in the low-gravity environment of space flight should be examined to establish an estimate of risk. The objective of this study is to synthesize data and conclusions from three areas of space biology and environmental health to arrive at rational risk assessment for radiations received by spacecraft crews: (1) the increased physiological demands of the space flight environment; (2) the effects of the space flight environment on physiological systems; and (3) the effects of radiation on physiological systems. One physiological system has been chosen: the immune response and its components, consisting of myeloid and lymphoid proliferative cell compartments. Best-case and worst-case scenarios are considered. In the worst case, a doubling of immune-function demand, accompanied by a halving of immune capacity, would reduce the endangering dose to a crew member to around 1 Gy.

Non-NASA Center↗
NASA NTRS1976

Increased concentration of Pseudomonas aeruginosa and Staphylococcus sp. in small animals exposed to aerospace environments

The effects of increased concentrations of PSEUDOMONAS AERUGINOSA AND STAPHYLOCOCCUS in the total bacterial flora of small animals exposed to simulated spacecraft environments were evaluated. Tests to detect changes in infectivity, effects of antibiotic treatments, immune responses to bacterial antigens, and effectiveness of immune responses in the experimental environment were conducted. The most significant results appear to be the differences in immune responses at simulated altitudes and the production of infection in the presence of a specific antibody.

Guthrie, R. K.↗
NASA NTRS1976

Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

Some immune response are effected through immunoglobulins (Ig), of which five classes have been recognized, namely, IgA, IgD, IgE, IgG, and IgM. Auto-antibodies associated with rheumatoid arthritis, termed rheumatoid factors (RF) react with antigenic determinants on IgG heavy chains. RF has predominant but not complete IgM specificity. This auto-antibody response was not detected in treated patients with primary brain tumors (where tissue is sequestered from the immune system by an intact bloodbrain barrier) or with multiple myeloma where humoral immunity is usually impaired. In addition, the prevalence of RF is not increased with solid tumors prior to initiation of chemotherapy or radiotherapy. It is proposed that RF is related to prior chemotherapy or radiotherapy of tumors anatomically accessible to immunologic tissues capable of antibody responses. A primary IgG response occurs, antigen-antibody complexes form, complexed IgG becomes immunologic, and an RF response results.

Towmey, J. J.↗
NASA NTRS1985

Effects of deceleration on the humoral antibody response in rats

Effects of hypergravity, simulated by chronic centrifugation, followed by a return to normal G (deceleration) on the immune system of rats were investigated. Two groups of male rats (28 days at 2.1 G, and 3.1 G) were compared to the control group (1.0 G). The animals were immunized by i.p. injections of sheep red blood cells on days 29, 42, and 57, and bled on days 36, 47, and 62. While the centrifuged rats ate and gainedsignificantly less than the control rats, the antibody titers and the organ/body mass ratios for the adrenal glands, kidneys, lungs, heart, and thymus were unaffected by gravity exposures, as were the values of the hematocrit and the white blood cell counts. It is concluded that deceleration does not adversely affect these particular aspects of the immune system.

Barone, R. P.↗
NASA NTRS1987

TOMS as a monitor of the ultraviolet radiation environment: Applications to photobiology

The flux of biologically relevant ultraviolet radiation that reaches the surface of the Earth varies with the ozone amount, surface reflectivity, and cloudcover. The Total Ozone Mapping Spectrometer (TOMS) provides information relevant to all three items. A recent application of satellite-based ozone measurements has been to develop climatologies of the biologically significant UV-B radiation reaching the Earth's surface. A growing body of research suggests that UV-B radiation tends to suppress the immune system of laboratory mice. At tropical latitudes, it is likely that parasitical diseases develop most readily in people who have experienced immune system suppression from UV-B exposure. The computed distribution of surface radiation combined with information on disease incidence may clarify the role of UV-B as a suppressor of the human immune system. TOMS used in conjunction with radiative transfer calculations can provide information of relevance in photobiology.

Frederick, John E.↗
NASA NTRS1988

Computer viruses

The worm, Trojan horse, bacterium, and virus are destructive programs that attack information stored in a computer's memory. Virus programs, which propagate by incorporating copies of themselves into other programs, are a growing menace in the late-1980s world of unprotected, networked workstations and personal computers. Limited immunity is offered by memory protection hardware, digitally authenticated object programs,and antibody programs that kill specific viruses. Additional immunity can be gained from the practice of digital hygiene, primarily the refusal to use software from untrusted sources. Full immunity requires attention in a social dimension, the accountability of programmers.

Denning, Peter J.↗
NASA NTRS1999

Locomotion in Lymphocytes is Altered by Differential PKC Isoform Expression

Lymphocyte locomotion is critical for proper elicitation of the immune response. Locomotion of immune cells via the interstitium is essential for optimal immune function during wound healing, inflammation and infection. There are conditions which alter lymphocyte locomotion and one of them is spaceflight. Lymphocyte locomotion is severely inhibited in true spaceflight (true microgravity) and in rotating wall vessel culture (modeled microgravity). When lymphocytes are activated prior to culture in modeled microgravity, locomotion is not inhibited and the levels are comparable to those of static cultured lymphocytes. When a phorbol ester (PMA) is used in modeled microgravity, lymphocyte locomotion is restored by 87%. This occurs regardless if PMA is added after culture in the rotating wall vessel or during culture. Inhibition of DNA synthesis also does not alter restoration of lymphocyte locomotion by PMA. PMA is a direct activator of (protein kinase C) PKC . When a calcium ionophore, ionomycin is used it does not possess any restorative properties towards locomotion either alone or collectively with PMA. Since PMA brings about restoration without help from calcium ionophores (ionomycin), it is infer-red that calcium independent PKC isoforms are involved. Changes were perceived in the protein levels of PKC 6 where levels of the protein were downregulated at 24,72 and 96 hours in untreated rotated cultures (modeled microgravity) compared to untreated static (1g) cultures. At 48 hours there is an increase in the levels of PKC & in the same experimental set up. Studies on transcriptional and translational patterns of calcium independent isoforms of PKC such as 8 and E are presented in this study.

Sundaresan, A.↗