Dysregulation of the immune system has been shown to be associated with space flight, and there have been several excellent reviews published regarding this subject. Causal factors for immune dysfunction include physiological stress, isolation, disrupted circadian rhythms, nutrition, and radiation. Also, microgravity itself may have a direct effect on immune cell function. Some of the alterations that have been observed following space flight (immediate post-flight testing) include altered: cytokine production patterns; NK cell function; leukocyte distribution; monocyte function; granulocyte function; T cell intracellular signaling; neuroendocrine responses; and leukocyte proliferation following activation. Due to the complexities associated with in-flight experiments, there have been comparatively few in-flight studies of immune function. Those that have been performed have found reactivation of latent herpes viruses during short duration flight and altered cell mediated immunity during long-duration flight. As a whole, these data strongly suggest that immune dysregulation is associated with space flight, regardless of duration. However, the precise in-flight nature of the dysregulation, especially as equilibrates over longer duration flights (distinct from launch/landing stresses) is not known.
One goal of NASA and the space life science community is to determine the clinical risks associated with prolonged space flight on human physiology, so that countermeasures may be developed prior to the initiation of exploration-class space missions. This need has been heightened by the impending deep space exploration program, which should be implemented by NASA over the next decade. An appropriate ground analog for space flight-associated immune dysregulation would offer a platform for ground evaluation of potential countermeasures. Choice of an appropriate ground analog is dependent on the physiological system of interest. The best analog for immune dysfunction would mimic on-orbit effects on human immunity, such as mission stress, adverse environment, isolation, etc. This study evaluated the NASA Extreme Environment Mission Operations (NEEMO) consisting of 14 day undersea deployment at the Aquarius station, as an analog for this phenomenon. Given the comparatively short duration, NEEMO is viewed as a Space Shuttle analog. NEEMO missions consist of actual (not simulated) deployment, real-time station lifestyle, and legitimate risk associated with saturation diving. For this study, assays included measures of adaptive immunity, viral reactivation and stress factors. This assay panel is similar to those currently employed to evaluate on-orbit changes, allowing direct ground-flight comparison.
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A total of 16 subjects participated in this study, representing the NEEMO 12, 13, and 14 missions. Informed consent was obtained from all subjects, and relevant institutional CPHS/IRB approvals were obtained. All NASA general immune and viral assessment methods used for this study, including immunophenotype analysis, T cell number, cytometric bead array analysis of cytokines, MHC tetramer analysis of viral specific T cell function, peptide stimulation for viral specific T cell function, and PCR for latent viral reactivation, were performed.
Some changes in leukocyte distribution, T cell function, cytokine production, virus specific immunity and viral reactivation that occur during NEEMO missions which are similar to those observed during or immediately following short-duration space flight. Unfortunately, six days prior may be too near to mission start to serve as an appropriate baseline measurement which is also the case for Shuttle and International Space Station (ISS) missions. The current NEEMO platform may have utility for short-duration, ground-based space flight immune research, such as investigations of mechanism or countermeasures validation. Longer NEEMO missions (>30 days) may serve as a model for ISS missions.
Crucian BE, Stowe RP, Mehta SK, Feuerecker M, Choukèr A, Quiriarte H, Pierson DL, and Sams CF. NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation. 18th IAA Humans in Space Symposium, Houston, Texas, April 11-15, 2011.
Cytomegalovirus - CMV, antibodies
Epstein-Barr virus - EBV, antibodies
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Latent viral reaction
Number and function of viral specific T cells
Peripheral leukocyte subset distribution
Plasma stress hormones
Saliva stress hormones
Saliva viral DNA
T cell function
Urine stress hormones
Urine viral DNA
Virus specific immunity
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
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the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
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