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Current Selection Filters |
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| Risk 8: Immune Dysfunction, Allergies and Autoimmunity |
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| Crosscutting Area : Human Health and Countermeasures |
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 Discipline : Immunology & Infection |
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| Description : Atopic and autoimmune diseases may occur due to long-term space flight effects on immune-regulatory pathways or on specific immune cells. |
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Context / Risk Factors :
This risk may be influenced by radiation, microgravity, isolation, stress (e.g., sleep deprivation, extreme environments, and nutritional deprivation), or crewmember genetics.
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| Justification / Rationale : In vitro studies have demonstrated that contributing risk factors of space flight collectively have a powerful effect upon the cells of the immune system: T cells, particularly CD4+ (helper) T cells, B cells, NK cells, monocyte/ macrophages/dendritic cells, hematopoietic stem cells and cytokine networks can be negatively affected. Alterations in one or more immune system regulatory network (i.e. cells or cell products) could affect homeostasis, which could result in allergic (atopic) or autoimmune disease. The relatively short time of the lunar mission (10-44 days) would tend to reduce the risk of developing immunodeficiency or atopic disease. The long-term exposure (>1 year) to deep-space radiation, to microgravity (> 2 years), and to other conditions of space flight during a Mars mission would offer the greatest challenge to the host immune system. |
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| Reference Missions :
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Risk Rating
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Current Countermeasures
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- Assessment of crewmembers for prior autoimmune or atopic disorders.
- Radiation shielding
- Monitor and limit exposure to radiation and other environmental factors
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Projected Countermeasures or Mitigations and Other Deliverables with their CRL/TRL scores
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- Definition of surrogate markers of immune function that will allow for the monitoring of immune cells and/or immune system compartments during a long-duration space flight
- Definition of the background of crewmembers to identify individuals more likely to develop autoimmune or atopic disease
- Detection systems for assessment of immune function [CRL 2]
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Research & Technology Questions
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| 8a |
What are the molecular and genetic mechanisms that are affected by space flight related environments (e.g., radiation, microgravity, stress, isolation, sleep deprivation, extreme environments, nutritional deficiency, and social interactions) that can result in the loss of immunoregulation/immune tolerance and/or affect innate/acquired immunity, respectively? |
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| 8b |
Can the effects on immune function (innate/acquired immunity), or dysfunction (loss of tolerance/immune surveillance) be summarized as a consequence of the conditions relating to each mission and/or its duration (i.e., 1-year ISS, 30-day lunar, 30-month Mars)? |
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| 8c |
What autoimmune diseases or allergies may affect astronauts exposed to space flight environments of different missions and/or durations? |
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| 8d |
Are there detection systems that can identify the first alterations in immune regulatory networks (identify surrogate markers of immune function/dysfunction) so that therapeutic interventions can be instituted? |
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| 8e |
What steps can be taken during space flight to modify immune function as it relates to autoimmunity or atopic disease? |
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| 8f |
Will it be possible to use immuno-regulatory agents to prevent immune imbalances with respect to the development of atopic or autoimmune diseases? |
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| 8g |
Will nutritional supplements be able to modify immune responses by working in concert with other immuno-modulators to reduce atopic and/or autoimmune disease? |
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| 8h |
What pharmalogical agents used during long-term space flights, or interactions between pharmalogical agents, negatively affect the immune system? |
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Related Risks
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Important References
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Aviles H, Belay T, Vance M, Sonnenfeld G. Increased levels of catecholamines correlate with decreased function of the immune system in the hindlimb-unloading rodent model of spaceflight (Abstract 107). Gravit Space Biol Bull. 17:56, 2003.
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Chinen J, Shearer WT. Immunosuppression induced by therapeutic agents and by environmental conditions. In Stiehm ER, ed. Immunologic disorders in infants and children, 5th Edition. Philadelphia: WB Saunders, in press, 2004.
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Chitnis T, Khoory SJ. Role of costimulatory pathways in the pathogenesis of multiple sclerosis and experimental autoimmune encephalitis. J Allergy Clin Immunol. 112:837-849, 2003.
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Dicello JF. The impact of the new biology on radiation risks in space. Health Phys. 85:94-102, 2003.
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Dicello JP. Cucinotta FA. Space radiation. Shankar Vinala Art No. sst036:1-8, 2003.
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Fedorenko B, Druzhinin S, Yudaeva L, Petrov V,Akatov Y, Snigiryova G, Novitskaya N, Shevchenko V, and Rubanovich A. Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on Mir station. Adv Space Res. 27(2):355-9, 2001.
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Graczyk PP. Caspase inhibitors as anti-inflammatory and antiapoptotic agent. Prog Med Chem. 39:1-72, 2003
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Greeneltch KM, Haudenschild CC, Keegan AD, Shi Y. The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-alpha production. Brain Behav Immun. 18(5):476-84, 2004.
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Gridley DS, Nelson GA, Peters LL, Kostenuik PJ, Bateman TA, Morony S, 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. 94:2095-2103.
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Gridley DS, Pecaut MJ, Dutta-Roy R, Nelson GA, Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: part I. Immunol Lett. 80:55-66, 2002.
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Grove DS, Pishak SA, and Matro AM. The effect of a 10-day spaceflight on the function, phenotype, and adhesion molecule expression of splenocytes and lymph node lymphocytes. Exp Cell Res. 219(1):102-9, 1995.
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Nelson RP Jr, Ballow M. Immunomodulation and immunotherapy: drugs, cytokines, cytokine receptors and antibodies. J Allergy Clin Immunol. 11:S720-S743, 2003.
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Pecaut MJ, Gridley DS, Smith AL, Nelson GA Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II. Immunol Lett. 80:67-73, 2002.
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Pecaut MJ, Nelson GA, Peters LL, Kostenuik PJ, Bateman TA, Morony S, et al. Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions. J Appl Physiol. 94:2085-2094, 2003.
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Shearer WT, Lee B-N, Cron SG, Rosenblatt HM, Smith EO, Lugg DJ, Nickolls PM, Sharp RM, Rollings K, Reuben JM. Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN- during the isolation of the Antarctic winter. J Allergy Clin Immunol. 109:854-857, 2002.
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Shearer WT, Sonnenfeld G. Alterations of immune responses in space travel. In: Mark M, ed. Encyclopedia of Space Science and Technology. NY, NY John Wiley & Sons, pp. 810-838, 2003.
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Shi YF, Devadas S, Greeneltch KM, Yin DL, Mufson R, Zhou JN. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology. Brain Behav Immun. 17:S18-S26, 2003.
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Shirai T, Magara KK, Motohashi S, Yamashita M, Kimura M, Suwazomo Y, et al. TH1-biased immunity induced by exposure to Antarctic winter. J Allergy Clin Immunol. 111:1353-1360.
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Sonnenfeld G, Butel JS, Shearer WT. Effects of the spaceflight environment of the immune system. Rev Environ Health. 18:1-17, 2003.
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Sonnenfeld G, Shearer WT. Immune function during spaceflight. Nutrition. 18:899-903, 2002.
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Stanislaus M, Bennett P, Guidal P, Danet G, Luongo J, Sutherland B, Gewirtz A. Effect of deep-space radiation on human hematopoietic stem cell function (Abstract 195). Exp Hematol. 195(Suppl 1):85, 2002.
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Sutherland BM, Bennett PV, Cintron-Torres N, Hada M, Trunk J, Monteleone D, Sutherland JC, Laval J, Stanislaus M, Gewirtz A. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation. J Radiat Res. (Tokyo) 43Suppl: S149-S152, 2002.
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Sutherland BM, Bennett PV, Georgakilas AG, Sutherland JC. Evaluation of number average length analysis in quantifying double strand breaks in genomic DNAs. Biochemistry. 42(11):3375-84, 2003.
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Sutherland BM, Georgakilas AG, Bennett PV, Laval J, Sutherland, JC. Quantifying clustered DNA damage induction and repair by gel electrophoresis, electronic imaging and number average length analysis, submitted, 2003.
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Torvey SE, Sundel RP. Autoimmune diseases. In Leung DYM, Sampson MA, Geha RS, Szefler SF, eds. Pediatric Allergy: Principles and Practice, Philadelphia: Mosby, pp. 159-169, 2003.
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Wei LX, Zhou JN, Roberts AI, Shi YF. Lymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the spleen and thymus. Cell Res. 13: 465-471, 2003.
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Zhang XR, Zhang L, Devadas S, Li L, Keegan AD, Shi YF. Reciprocal expression of TRAIL and CD95L in Th1 and Th2 cells: role of apoptosis in T helper subset differentiation. Cell Death Differ. 10(2):203-10, 2003.
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