Document Type : Scientific extension


Aerospace Research Institute, Ministry of Science, Research and Technology, Tehran, Iran


The immune system is a complex network of biological structures and processes that by reducing its function or slightly modifying any of its aspects can increase the risk of disease. Research suggests that gravity changes cause alterations in the immune system. This could also lead to conditions where astronauts suffer from skin irritation, abnormal allergies orreactivation of latent viruses. Furthermore, several bacterial strains can proliferate more readily in space which may be related to human reduced immunity. Also, it is observed that some immune cells are impaired and there are changes in the amount of protein produced by these cells. Hence, the weakening of the immune system due to space flight is an area of research that should be fully evaluated in order to maintain the homeostasis of body under such conditions. This article briefly describes the microgravity effects on the immune system, and the results could have ground application in addition to implications for the flight crew.


[1]     Frippiat, J-P, et al., Towards human exploration of space: The THESEUS review series on immunology research priorities. npj Microgravity. Vol. 2, 2016, p. 16040.
[2]     Guéguinou, N. and et al., "Stress response and humoral immune system alterations related to chronic hypergravity in mice," Psychoneuroendocrinology, Vol. 37, No. 1,  2012,  pp. 137-47.
[3]     Chen, Y. and et al., Effect of Long-Term Simulated Microgravity on Immune System and Lung Tissues in Rhesus Macaque," Inflammation. Vol. 40, No. 2, 2017, pp. 589-600.
[4]     Sepiashvili, R., "Functional system of immune homeostasis," Allergol Immunopatol, Vol. 4, No. 2, 2003, p. 5.
[5]     Sonnenfeld, G., "The immune system in space and microgravity," Medicine & Science in Sports & Exercise, Vol. 34, No. 12, 2002, pp. 2021-2027.
[6]     Crucian, BE, et al., "Plasma cytokine concentrations indicate that in vivo hormonal regulation of immunity is altered during long-duration spaceflight," Journal of Interferon & Cytokine Research, Vol. 34, No 10, 2014, pp. 778-86.
[7]     Knight, V, Couch, RB, Landahl, HD., "Effect of lack of gravity on airborne infection during space flight," Jama, Vol. 214, No. 3, 1970, pp. 513-8.
[8]     Cogoli, A., Tschopp, A., Fuchs-Bislin, P., Cell sensitivity to gravity, Science, Vol. 225, 1984, pp. 228-231.
[9]     Sonnenfeld, G., "Space flight modifies T cell activation—role of microgravity," Journal of leukocyte biology, Vol. 92, No. 6,  2012, pp. 1125-1126.
[10]  Chang, TT. and et al., "The Rel/NF-κB pathway and transcription of immediate early genes in T cell activation are inhibited by microgravity," Journal of leukocyte biology, Vol. 92, No. 6, 2012, pp. 1133-45.
[11]  Stowe RP. and et al., "Leukocyte subsets and neutrophil function after short-term spaceflight," Journal of leukocyte biology, Vol. 65, No. 2, 1999, pp. 179-86.
[12]  Kaur, I. and et al., "Changes in monocyte functions of astronauts," Brain, behavior, and immunity, Vol. 19, No. 6, 2005, pp. 547-54.
[13]  Kaur, I. and et al., "Effect of spaceflight on ability of monocytes to respond to endotoxins of gram-negative bacteria," Clinical and Vaccine Immunology, Vol. 15, No. 10, 2008, pp. 1523-8.
[14]  Nichols, HL, Zhang, N, Wen, X., "Proteomics and genomics of microgravity," Physiological genomics, Vol. 26, No. 3, 2006, pp. 163-71.
[15]  Frippiat, J-P., "Contribution of the urodele amphibian Pleurodeles waltl to the analysis of spaceflight-associated immune system deregulation," Molecular immunology, Vol. 56, No. 4, 2013, pp. 434-41.
[16]  Grimm, D. and et al., "How and why does the proteome respond to microgravity?," Expert Review of Proteomics, Vol. 8, No. 1, 2011, pp. 13-27.
[17]  Gueguinou, N. and et al., "Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit?," Journal of leukocyte biology. Vol. 86, No. 5, 2009, pp. 1027-38.
[18]  Pietsch, J, et al., "The effects of weightlessness on the human organism and mammalian cells," Current molecular medicine, Vol. 11, No. 5,  2011, pp. 350-64.
[19]  Johnston, RS. and Dietlein, LF., editors. Biomedical results from Skylab, NASA SP-377. Biomedical Results from Skylab; 1977.
[20]  Crucian B, et al., "A case of persistent skin rash and rhinitis with immune system dysregulation onboard the International Space Station," The Journal of Allergy and Clinical Immunology: In Practice, Vol. 4, No. 4, 2016, pp. 759-62. e8.
[21]  Crucian, B, et al., "Incidence of clinical symptoms during long-duration orbital spaceflight," International journal of general medicine, No. 9, 2016, p. 383.
[22]  Baqai, FP. and et al., "Effects of spaceflight on innate immune function and antioxidant gene expression," Journal of applied physiology,  Vol. 106, No. 6, 2009, pp. 1935-1942.
[23]  Gridley, DS. and et al., "Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines, erythrocytes, and platelets," J Appl Physiol, Vol. 94, No. 5, 2003, pp. 2095-2103.
[24]  Evans, Jr. CH. and Ball, JR., Safe passage: astronaut care for exploration missions, National Academies Press, 2001.
[25]  Decelle, J., Taylor, G., "Autoflora in the upper respiratory tract of Apollo astronauts," Applied and environmental microbiology, Vol. 32, No. 5, 1976, pp. 659-65.
[26]  Pierson, DL., Microbial contamination of spacecraft, Gravitational and Space Research, Vol. 14, No. 2, 2007, pp. 1-6.
[27]  Ilyin, V., Microbiological status of cosmonauts during orbital spaceflights on Salyut and Mir orbital stations, Acta astronautica, Vol. 56, No.9,  2005, pp. 839-50.
[28]  Novikova, N., "Review of the knowledge of microbial contamination of the Russian manned spacecraft.," Microbial ecology, Vol. 47, No. 2, 2004, pp. 127-32.
[29]  Berry, CA., "Summary of medical experience in the Apollo 7 through 11 manned spaceflights,"  Recent Advances in Aerospace Medicine: Springer; 1970. p. 3-41.
[30]  Puleo, J. and et al., "Microbiological profiles of four Apollo spacecraft," Applied microbiology, Vol. 26, No. 6, 1973, pp. 838-45.
[31]  Taylor, GR., "Space microbiology," Annual Reviews in Microbiology, Vol. 28, No. 1, 1974, pp. 121-37.
[32]  Hammond, TG. and et al., "Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle," Physiological genomics, Vol. 3, No. 3, 2000, pp. 163-73.
[33]  Collister, M. and et al., YIL113w encodes a functional dual‐specificity protein phosphatase which specifically interacts with and inactivates the Slt2/Mpk1p MAP kinase in S. cerevisiae. FEBS letters, Vol. 527, No. 1-3, 2002, pp. 186-92.
[34]  Sonnenfeld, G., "Space flight, microgravity, stress, and immune responses," Advances in Space Research, Vol. 23, No. 12, 1999, pp. 1945-53.
[35]  Leys, N. and et al., "Space flight effects on bacterial physiology," Journal of biological regulators and homeostatic agents, Vol. 18, No. 2, 2004, pp. 193-199.
[36]  Fukuda, T. and et al., "Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 470, No. 2, 2000, pp. 125-32.
[37]  Chopra, V. and et al., "Alterations in the virulence potential of enteric pathogens and bacterial–host cell interactions under simulated microgravity conditions," Journal of Toxicology and EnvironmentalHealth, Part A., Vol. 69, No. 14, 2006, pp. 1345-70.
[38]  Altenburg, SD., Nielsen-Preiss, SM., Hyman, LE., "Increased filamentous growth of Candida albicans in simulated microgravity," Genomics, proteomics & bioinformatics, Vol. 6. No. 1,2008, pp. 42-50.
[39]  Nickerson, CA. and et al., "Microgravity as a novel environmental signal affecting Salmonella enterica serovar Typhimurium virulence," Infection and immunity, Vol. 68, No. 6, 2000, pp. 3147-52.
[40]  Wilson, JW. and et al., "Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon," Proceedings of the National Academy of Sciences, Vol. 99, No. 21, 2002, pp. 13807-13812.
[41]  Wilson, J. and et al., "Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq," Proceedings of the National Academy of Sciences, Vol. 104, No. 41, 2007, pp. 16299-304.
[42]  Durnova, G., Kaplansky, A., Portugalov, V., Effect of a 22-day space flight on the lymphoid organs of rats," Aviation, space, and environmental medicine, Vol. 47, No. 6,  1976, pp. 588-91.
[43]  Steffen, J. and Musacchia, X., "Thymic involution in the suspended rat: adrenal hypertrophy and glucocorticoid receptor content," Aviation, space, andenvironmental medicine, Vol. 57, No. 2,  1986, pp. 162-7.
[44]  Pecaut, MJ., Simske, SJ. and Fleshner, M., "Spaceflight induces changes in splenocyte subpopulations: effectiveness of ground-based models," American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 279, No. 6, 2000, pp. R2072-R8.
[45]  Chapes, S. and et al., Effects of space flight and IGF-1 on immune function," Advances in Space Research, Vol. 23, No. 12, 1999, pp. 1955-64.
[46]  Chapes, SK. and et al., "Effects of spaceflight and PEG-IL-2 on rat physiological and immunological responses," Journal of applied physiology, Vol. 86, No. 6, 1999, pp. 2065-76.
[47]  Congdon, C. and et al., "Lymphatic tissue changes in rats flown on Spacelab Life Sciences-2," Journal of applied physiology, Vol. 81, No. 1, 1996, pp. 172-7.
[48]  Gould, CL. and et al., "Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the space shuttle," Aviation, space, and environmental medicine, Vol. 58, No. 10, 1987, pp. 983-6.
[49]  Grove, DS., Pishak, SA. and Mastro, AM., "The effect of a 10-day space flight on the function, phenotype, and adhesion molecule expression of splenocytes and lymph node lymphocytes, Experimental cell research, Vol. 219, No. 1, 1995, pp. 102-9.
[50]  Vernikos, J. Human, "physiology in space," Bioessays, Vol. 18, No. 12, 1996, pp. 1029-37.
[51]  Gridley, DS. and et al., "Spaceflight effects on T lymphocyte distribution, function and gene expression," Journalof applied physiology, Vol. 106, No. 1,  2009, pp. 194-202.
[52]  Mills, PJ. and et al., "Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration," Psychosomatic medicine, Vol. 63, No. 6,  2001, pp. 886-90.
[53]  Rykova M, Antropova E, Larina I, Morukov B., "Humoral and cellular immunity in cosmonauts after the ISS missions," Acta Astronautica. Vol. 18, No. 7, 2008, pp. 697-705.
[54]  Kaur, I. and et al., "Changes in neutrophil functions in astronauts," Brain, behavior, and immunity, Vol. 18, No. 5,2004, pp. 443-50.
[55]  Fitzgerald, KA., Rowe, DC., Golenbock, DT., "Endotoxin recognition and signal transduction by the TLR4/MD2-complex" Microbes and Infection, Vol. 6, No. 15, 2004, pp. 1361-7.
[56]  Miyake, K., "Innate recognition of lipopolysaccharide by Toll-like receptor 4–MD-2," Trends in microbiology, Vol. 12, No. 4, 2004, pp. 186-92.
[57]  Mehta, SK. and et al., "Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight," Journal of applied physiology, Vol. 91, No. 4,  2001, pp. 1814-8.
[58]  Rykova, MP. and et al., "Effect of spaceflight on natural killer cell activity," Journal of Applied Physiology, Vol. 37, No. 2, 1992, pp. S196-S200.
[59]  Sonnenfeld, G. and et al., "Spaceflight alters immune cell function and distribution," Journal of applied physiology, Vol. 73, No. 2, 1992, pp. S191-S5.
[60]  Ichiki, A. and et al., "Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells," Journal of leukocyte biology,  Vol. 60, No. 1, 1996, pp. 37-43.
[61]  Boonyaratanakornkit, JB. and et al., "Key gravity-sensitive signaling pathways drive T cell activation," The FASEB journal, Vol. 19, No. 14, 2005, pp. 2020-2.
[62]  Cohrs, RJ. and et al., "Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts," Journal of medical virology, Vol. 80, No. 6, 2008, pp. 1116-22.
[63]  Mehta, S. and et al., "Reactivation of latent viruses is associated with increased plasma cytokines in astronauts," Cytokine, Vol. 61, No. 1, 2013, pp. 205-9.
[64]  Pierson, D. and et al., "Epstein–Barr virus shedding by astronauts during space flight," Brain, behavior, and immunity, Vol. 19, No. 3, 2005, pp. 235-42.
[65]  Stowe, RP. and et al., "Immune responses and latent herpesvirus reactivation in spaceflight," Aviation, space, and environmental medicine, Vol. 72, No. 10, 2001, pp. 884-91.
[66]  Rykova, M., "Immune system of Russian cosmonauts after orbital space flights," Human Physiology, Vol. 39, No. 5, 2013,  pp. 557-66.
[67]  Gaignier, F. and et al., "Three weeks of murine hindlimb unloading induces shifts from B to T and from th to tc splenic lymphocytes in absence of stress and differentially reduces cell-specific mitogenic responses," PLOS one, Vol. 9, No. 3, 2014, pp. e92664.
[68]  Hughes-Fulford, M., Chang, TT., Martinez, EM., Li, C-F., "Spaceflight alters expression of microRNA during T-cell activation," The FASEB Journal, Vol. 29, No. 12, 2015, pp. 4893-900.
[69]  Meloni, MA., Galleri, G., Pippia, P., Cogoli-Greuter, M., "Cytoskeleton changes and impaired motility of monocytes at modelled low gravity," Protoplasma, Vol. 229, No. 2, 2006, pp. 243-9.
[70]  Janmey, PA., "The cytoskeleton and cell signaling: component localization and mechanical coupling," Physiological reviews, Vol. 78, No. 3, 1998, pp. 763-81.
[71]  INGBER, D., "How cells (might) sense microgravity," The FASEB Journal, Vol. 13, No. 9001, 1999, pp. S3-S15.
[72]  Thiel,, CS. and et al., "Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity," Cell Communication and Signaling, Vol. 10, No. 1, 2012, p. 1.
[73]  Battista, N. and et al., "5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: data from the ROALD experiment," The FASEB Journal. Vol. 26, No. 5, 2012, pp. 1791-8.
[74]  Tauber, S. and et al., "Signal transduction in primary human T lymphocytes in altered gravity–results of the MASER-12 suborbital space flight mission," Cell Communication and Signaling, Vol. 11, No. 1, 2013, p. 32.
[75]  Crucian, BE., Stowe, RP., Pierson, DL. and Sams, CF., "Immune system dysregulation following short-vs long-duration spaceflight," Aviation, space, and environmental medicine, Vol. 79, No. 9, 2008, pp. 835-43.
[76]  Crucian, B. and et al., "Alterations in adaptive immunity persist during long-duration spaceflight," npj Microgravity, Vol. 1, 2015, p. 15013.
[77]  Crucian, B. and et al., "Immune system dysregulation occurs during short duration spaceflight on board the space shuttle," Journal of clinical immunology, Vol. 33, No. 2, 2013, pp. 456-65.
[78]  Wen, X., Yang, G., Wang, T. and Hu, P., "Effects of simulated weightlessness on T cell subpopulations and activity of IL-2 and IL-6 in mice," Hang tian yi xue yu yi xue gong cheng= Space medicine & medical engineering, Vol. 14, No. 1, 2001, pp. 60-2.
[79]  Lewis, ML. and et al., "Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat)" The FASEB Journal, Vol. 12, No. 11, 1998, pp. 1007-18.
[80]  Dinarello, CA., Novick, D., Kim, S. and Kaplanski, G., "Interleukin-18 and IL-18 binding protein," Frontiers in immunology, Vol. 4,  2013.
[81]  Hundsberger, H. and et al., "TNF: a moonlighting protein at the interface between cancer and infection," Frontiers in bioscience: a journal and virtual library,  Summary of medical experience in the Apollo 7 through 11 manned spaceflightol. 13, 2007, pp. 5374-86.
[82]  Konstantinova, IV., Rykova, M., Lesnyak, AT. and Antropova, EA., "Immune changes during long-duration missions," Journal of Leukocyte Biology, Vol. 54, No. 3, 1993, pp. 189-201.
[83]  Michurina, T., Domaratskaya, E., Nikonova, T. and Khrushchov, N., "Blood and clonogenic hemopoietic cells of newts after the space flight," Advances in Space Research, Vol. 17, No. 6-7, 1996, pp. 295-8.
[84]  Bascove, M. and et al., "Spaceflight-associated changes in immunoglobulin VH gene expression in the amphibian Pleurodeles waltl," The FASEB Journal, Vol. 23, No. 5, 2009, pp. 1607-15.
[85]  Bascove, M, and et al., "Decrease in antibody somatic hypermutation frequency under extreme, extended spaceflight conditions," The FASEB Journal, Vol. 25, No. 9, 2011, pp. 2947-55.
[86]  Huin-Schohn, C. and et al., "Gravity changes during animal development affect IgM heavy-chain transcription and probably lymphopoiesis," The FASEB Journal,  Vol. 27, No. 1,2013, pp. 333-41.
[87]  Lescale, C. and et al., "Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging," The FASEB Journal, Vol. 29, No. 2, 2015, pp. 455-63.
[88]  Schaerlinger, B., Bascove, M., Frippiat, J-P., "A new isotype of immunoglobulin heavy chain in the urodele amphibian Pleurodeles waltl predominantly expressed in larvae" Molecular immunology, Vol. 45, No. 3, 2008, pp. 776-86.
[89]  Maule, J. and et al., "Antibody binding in altered gravity: implications for immunosorbent assay during space flight," Journal of gravitational physiology: a journal of the International Society for Gravitational Physiology, Vol. 10, No. 2,  2003, pp. 47-55.