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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2005

Use of animal models for space flight physiology studies, with special focus on the immune system

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

Review↗
NASA NTRS2002

Maintaining the Body's Immune System: Incidence of Latent Virus Shedding During Space Flight

Your body protects you from illness with its own security system - the immune system. This system keeps illness at bay not only by mounting a defense against foreign organisms, but also by controlling the population of bacteria and viruses that normally live in your body. But there's no need to panic: certain microbes can actually exist in your body without causing illness. Some bacteria are even beneficial - like the E. coli in the large intestine that are an important source of vitamin K. While viruses are not exactly considered beneficial, they can also inhabit the human body without causing immediate harm or infection. A good example is the herpes simplex virus type 1 (HSV1), more commonly known as cold sores or fever blisters. This virus infects 70 to 80 percent of all adults but remains latent much of the time. While latent, the virus within cells remains dormant. Activation of the dormant virus causes it to make copies of itself (known as replication) constantly detectable in body fluids such as urine or saliva in a process called shedding. When a person becomes sick or stressed, however, this weakened condition allows the virus to reactivate and multiply. These elevated levels may be enough to produce symptoms, but shedding can also occur without symptoms. This ability to shed without showing signs of infection, or asymptomatic shedding, is of great interest, as it increases the chances of infecting others. The stresses associated with space flight - adapting to microgravity, isolation from family and friends, living and working in a confined space, sleep deprivation, and busy schedules, to name but a few - may weaken astronauts' immune systems, leaving them at greater risk of viral reactivation. Members of the STS-107 crew will participate in this experiment, Incidence of Latent Viral Shedding in Space Flight, to help scientists understand how reactivation works in space, and at what level replication reaches before symptoms begin to show. This study also promises more insight into the behavior of the larger virus family, herpesvirus, which will help us understand how to prevent infection in populations on Earth and reactivation in those already infected.

Pierson, Duane↗
NASA NTRS2002

Artificial Immune System Approaches for Aerospace Applications

Artificial Immune Systems (AIS) combine a priori knowledge with the adapting capabilities of biological immune system to provide a powerful alternative to currently available techniques for pattern recognition, modeling, design, and control. Immunology is the science of built-in defense mechanisms that are present in all living beings to protect against external attacks. A biological immune system can be thought of as a robust, adaptive system that is capable of dealing with an enormous variety of disturbances and uncertainties. Biological immune systems use a finite number of discrete "building blocks" to achieve this adaptiveness. These building blocks can be thought of as pieces of a puzzle which must be put together in a specific way-to neutralize, remove, or destroy each unique disturbance the system encounters. In this paper, we outline AIS models that are immediately applicable to aerospace problems and identify application areas that need further investigation.

KrishnaKumar, Kalmanje↗
NASA NTRS2002

Total-body irradiation with high-LET particles: acute and chronic effects on the immune system

Although the immune system is highly susceptible to radiation-induced damage, consequences of high linear energy transfer (LET) radiation remain unclear. This study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion (56Fe(26)) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and 113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (28Si) was euthanized on day 113. On day 4 after 56Fe irradiation, dose-dependent decreases were noted in spleen and thymus masses and all major leukocyte populations in blood and spleen. The CD19(+) B lymphocytes were most radiosensitive and NK1.1(+) natural killer (NK) cells were most resistant. CD3(+) T cells were moderately radiosensitive and a greater loss of CD3(+)/CD8(+) T(C) cells than CD3(+)/CD4(+) T(H) cells was noted. Basal DNA synthesis was elevated on day 4, but response to mitogens and secretion of interleukin-2 and tumor necrosis factor-alpha were unaffected. Signs of anemia were noted. By day 113, high B cell numbers and low T(C) cell and monocyte percents were found in the 2.0 Gy 56Fe group; the 2.0 Gy 2)Si mice had low NK cells, decreased basal DNA synthesis, and a somewhat increased response to two mitogens. Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.

NASA Discipline Radiation Health↗
NASA NTRS2024

Flow Cytometry Methods to Monitor Immune System Dysregulation in Astronauts

Persistent immune system dysregulation has been documented to occur in astronauts participating in orbital spaceflight onboard the International Space Station. The phenomenon consists of reductions in T and NK cell function, altered cytokine profiles, persistent inflammation, and the subclinical reactivation of latent herpesviruses. In select crewmembers the dysregulation does actually lead to clinical symptoms, primarily atypical allergy or atopic dermatitis/zoster. Flow cytometry has served a central role defining the ‘immune assessment’ panel of assays that allow monitoring of astronauts. The cytometry assays which have been utilized include: 1. Peripheral leukocyte subsets 2. T cell function 3. Monocyte function 4. NK cell function 5. Intracellular cytokine analysis 6. Virus-specific T cell number (tetramer assay) 7. Virus-specific T cell function (peptide stimulation) 8. Leukocyte-bacterial challenge cytometry 9. Cytometric bead/multiplex array (soluble proteins) The use of these assays has been validated through various ISS flight investigations to define, to varying degrees, both in-flight, and post-flight immune system alterations. The kinetics of the dysregulation through the various phases of spaceflight, as well as post-flight recovery, have also been documented. To allow the science to occur within the orbital constraints of a spaceflight investigation, particular sample collection and processing techniques were developed compatible with the delays associated with terrestrial processing of in-flight samples. A subset of the assays has been adapted to routine monitoring of astronauts via a NASA ‘ISS Standard Measures’ activity, with the data from a specific crew then provided to all science investigators for that particular mission. This battery of cytometry assays has also been applied, through ground investigations, to several terrestrial ‘spaceflight analog’ populations. The purpose was to validate the analog which most closely replicates the in-flight observed pattern of alterations, generally believed to be winterover at an Antarctica station. To assist in determination of clinical risk, the assay panel has also been applied to investigations of various terrestrial patient populations, particularly zoster patients. As NASA is initiating crewed lunar missions via the ‘Artemis’ program, deployment of a miniaturized, microgravity-compatible flow cytometer, would be extremely beneficial to allow real time monitoring of crewmembers. Real time medical data could influence use of several countermeasures options during deep space missions. Several such instruments have been developed and validated to varying degrees of success. Assay details and summary findings across the various flight and ground platforms will be presented, as will current status in developing such technology for in-flight use.

Brian Crucian↗
NASA NTRS2011

Clonal Selection Based Artificial Immune System for Generalized Pattern Recognition

The last two decades has seen a rapid increase in the application of AIS (Artificial Immune Systems) modeled after the human immune system to a wide range of areas including network intrusion detection, job shop scheduling, classification, pattern recognition, and robot control. JPL (Jet Propulsion Laboratory) has developed an integrated pattern recognition/classification system called AISLE (Artificial Immune System for Learning and Exploration) based on biologically inspired models of B-cell dynamics in the immune system. When used for unsupervised or supervised classification, the method scales linearly with the number of dimensions, has performance that is relatively independent of the total size of the dataset, and has been shown to perform as well as traditional clustering methods. When used for pattern recognition, the method efficiently isolates the appropriate matches in the data set. The paper presents the underlying structure of AISLE and the results from a number of experimental studies.

pattern recognition↗
NASA NTRS2005

Countermeasure for space flight effects on immune system: nutritional nucleotides

Microgravity and its environment have adverse effects on the immune system. Abnormal immune responses observed in microgravity may pose serious consequences, especially for the recent directions of NASA for long-term space missions to Moon, Mars and deep Space exploration. The study of space flight immunology is limited due to relative inaccessibility, difficulty of performing experiments in space, and inadequate provisions in this area in the United States and Russian space programs (Taylor 1993). Microgravity and stress experienced during space flights results in immune system aberration (Taylor 1993). In ground-based mouse models for some of the microgravity effects on the human body, hindlimb unloading (HU) has been reported to cause abnormal cell proliferation and cytokine production (Armstrong et al., 1993, Chapes et al. 1993). In this report, we document that a nutritional nucleotide supplementation as studied in ground-based microgravity analogs, has potential to serve as a countermeasure for the immune dysfunction observed in space travel.

NASA Center JSC↗
NASA NTRS2018

Radiation and the Immune System

Radiation has profound effects on the immune system. This makes it particularly important to study in order to protect astronauts venturing into deep space and cancer patients considering radiotherapy treatments. Beyond the Earth's magentic field lies galactic cosmic radiation, which contains heavy ion based rays. Immune alterations in response to radiation depends on factors such as the type and amount of radiation, and potentially even the genes of the individual being exposed. In order to study the effects of cosmic radiation on the immune system, we are exposing primary human immune cells to various types and amounts of radiation. To measure sensitivity to radiation, we are quantifying the DNA damage within the cells before irradiation, 4 hours after irradiation, and 24 hours after irradiation. DNA damage is visualized by fluorescently staining for known DNA repair proteins, which get recruited to the site of damage within a cell. These results will be analyzed to search for correlations between immune cell responses and the type of radiation, amount of radiation, or any genetic markers present in the human blood donors. We will also be attempting to determine which specific immune cells are most suspectible to radiation damage. These correlations and discoveries will contribute to making long duration human deep space exploration a possibility, and can even be used to design more personalized and effective radiation treatments for cancer patients.

Malkani, Sherina S.↗
NASA NTRS2014

Pulmonary and Systemic Immune Response to Chronic Lunar Dust Inhalation

Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra‐fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non‐exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post‐exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL‐1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL‐1b and IL‐6, and decreased IL‐2 production. Conclusion: Lunar dust inhalation results in significant lung inflammation, and some systemic effects, that does not resolve through 13 weeks. Lunar dust may therefore represent a crew health risk during sortie or long‐duration Lunar missions.

Crucian, Brian↗
NASA NTRS1995

Effects of Space Missions on the Human Immune System: A Meta-Analysis

Future spaceflight will require travelers to spend ever-increasing periods of time in microgravity. Optimal functioning of the immune system is of paramount importance for the health and performance of these travelers. A meta-analysis statistical procedure was used to analyze immune system data from crew members in United States and Soviet space missions from 8.5 to 140 days duration between 1968 and 1985. Ten immunological parameters (immunoglobulins A, G, M, D, white blood cell (WBC) count, number of lymphocytes, percent total lymphocytes, percent B lymphocytes, percent T lymphocytes, and lymphocyte reactivity to mitogen) were investigated using multifactorial, repeated measure analysis of variance. With the preflight level set at 100, WBC count increased to 154 +/- 14% (mean +/- SE; p less than or equal to 0.05) immediately after flight; there was a decrease in lymphocyte count (83 +/- 4%; p less than or equal to 0.05) and percent of total lymphocytes (69 +/- 1%; p less than or equal to 0.05) immediately after flight, with reduction in RNA synthesis to phytohemagglutinin (PHA) to 51 +/- 21% (p less than or equal to 0.05) and DNA synthesis to PHA to 61 +/- 8% (p less than or equal to 0.05) at the first postflight measurement. Thus, some cellular immunological functions are decreased significantly following spaceflight. More data are needed on astronauts' age, aerobic power output, and parameters of their exercise training program to determine if these immune system responses are due solely to microgravity exposure or perhaps to some other aspect of spaceflight.

Greenleaf, J. E.↗
NASA NTRS2005

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

NASA Discipline Regulatory Physiology↗
NASA NTRS2003

Effects of the space flight environment on the immune system

Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

NASA Discipline Regulatory Physiology↗
NASA NTRS2005

Artificial Immune System for Recognizing Patterns

A method of recognizing or classifying patterns is based on an artificial immune system (AIS), which includes an algorithm and a computational model of nonlinear dynamics inspired by the behavior of a biological immune system. The method has been proposed as the theoretical basis of the computational portion of a star-tracking system aboard a spacecraft. In that system, a newly acquired star image would be treated as an antigen that would be matched by an appropriate antibody (an entry in a star catalog). The method would enable rapid convergence, would afford robustness in the face of noise in the star sensors, would enable recognition of star images acquired in any sensor or spacecraft orientation, and would not make an excessive demand on the computational resources of a typical spacecraft. Going beyond the star-tracking application, the AIS-based pattern-recognition method is potentially applicable to pattern- recognition and -classification processes for diverse purposes -- for example, reconnaissance, detecting intruders, and mining data.

Huntsberger, Terrance↗
NASA NTRS1984

The unresponsiveness of the immune system of the rat to hypergravity

The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

Scibetta, S. M.↗
NASA NTRS1999

Study Design to Test the Hypothesis That Long-Term Space Travel Harms the Human and Animal Immune Systems

The potential threat of immunosuppression and abnormal inflammatory responses in long-term space travel, leading to unusual predilection for opportunistic infections, malignancy, and death, is of ma or concern to the National Aeronautics and Space Administration (NASA) Program. This application has been devised to seek answers to questions of altered immunity in space travel raised by previous investigations spanning 30-plus years. We propose to do this with the help of knowledge gained by the discovery of the molecular basis of many primary and secondary immunodeficiency diseases and by application of molecular and genetic technology not previously available. Two areas of immunity that previously received little attention in space travel research will be emphasized: specific antibody responses and non-specific inflammation and adhesion. Both of these areas of research will not only add to the growing body of information on the potential effects of space travel on the immune system, but be able to delineate any functional alterations in systems important for antigen presentation, specific immune memory, and cell:cell and cell:endothelium interactions. By more precisely defining molecular dysfunction of components of the immune system, it is hoped that targeted methods of prevention of immune damage in space could be devised.

Shearer, William T.↗
NASA NTRS2007

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 deg. head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of EBV and CMV was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in plasma cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 10(exp 6) PBMCs. These data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Mehta, Satish↗
NASA NTRS2007

Monitoring Immune System Function and Reactivation of Latent Viruses in the Artificial Gravity Pilot Study

Numerous studies have indicated that dysregulation of the immune system occurs during or after spaceflight. Using 21 day -6 degrees head-down tilt bed rest as a spaceflight analog, this study describes the effects of artificial gravity (AG) as a daily countermeasure on immunity, stress and reactivation of clinically important latent herpes viruses. The specific aims were to evaluate psychological and physiological stress, to determine the status of the immune system, and to quantify reactivation of latent herpes viruses. Blood, saliva, and urine samples were collected from each participating subject at different times throughout the study. An immune assessment was performed on all treatment and control subjects that consisted of a comprehensive peripheral immunophenotype analysis, intracellular cytokine profiles and a measurement of T cell function. The treatment group displayed no differences throughout the course of the study with regards to peripheral leukocyte distribution, cytokine production or T cell function. Shedding of Epstein barr virus (EBV), Cytomegalovirus (CMV), and Varicella zoster virus (VZV) was quantified by real time PCR in saliva and urine samples, respectively. There was no significant difference in CMV DNA in the treatment group as compared to the control group. EBV and VZV on the other hand showed a mild reactivation during the study. There were no significant differences in cortisol between the control and treatment groups. In addition, no significant differences between antiviral antibody titers (EBV-VCA, -EA, -EBNA, CMV) or tetramer-positive (EBV, CMV) were found between the two groups. EBV DNA copies in blood were typically undetectable but never exceeded 1,500 copies per 106 PBMCs. Overall, these data indicate that the artificial gravity countermeasure and the 21 day head-down tilt bed rest regimen had no observable adverse effect on immune function.

Mehta, Satish K.↗
NASA NTRS2011

NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation?

This poster paper reviews the use of 14 day undersea missions as a possible analog for short duration spaceflight for the study of immune system dysregulation. Sixteen subjects from the the NASA Extreme Enviro nment Mission Operations (NEEMO) 12, 13 and 14 missions were studied for immune system dysregulation. The assays that are presented in this poster are the Virleukocyte subsets, the T Cell functions, and the intracellular/secreted cytokine profiles. Other assays were performed, but are not included in this presntation.

Crucian, B. E.↗