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At least 307 records · Page 17

Effects of the space flight environment on man's immune system. II - Lymphocyte counts and reactivity.

The present studies were undertaken to assess the effects of the environment of space flights on the cellular division of the human immune system. Peripheral blood absolute lymphocyte counts were determined at various preflight and postflight intervals for the 21 crewmen of Apollo Missions 7-13. Mean lymphocyte numbers tended to exhibit a delayed significant but fluctuating increase shortly after recovery, although a variety of responses was seen in individual astronauts. The in vitro reactivity of lymphocytes, reflected by RNA and DNA synthesis rates by unstimulated and PHA-stimulated lymphocytes tissue-cultured preflight and postflight from the same participants, was found to remain within previously established normal ranges. These results indicate that functional integrity of cellular immune potential as reflected by in vitro techniques is maintained during this spaceflight experience.

Fischer, G. L.↗

Microflora analysis of a child with severe combined immune deficiency

The paper presents a microflora analysis of a 5-year-old male child with severe combined immune deficiency who was delivered by Caesarean section and continuously maintained in an isolator. Despite precautions, it was found that the child had come in contact with at least 54 different microbial contaminants. While his skin autoflora was similar to that of a reference group of healthy male adults in numbers of different species and the number of viable cells present per square centimeter of surface area, the subject's autoflora differed from the reference group in that significantly fewer anaerobic species were recovered from the patient's mouth and feces. It is suggested that the child's remaining disease free shows that the reported bacteria are noninvasive or that the unaffected components of the child's immune defense mechanisms are important.

Taylor, G. R.↗

Effect of simulated weightlessness on the immune system in rats

Rats suspended in a model system designed to simulate many aspects of weightlessness were immunized with sheep red blood cells. Parameters measured on these and control rats included titers of anti-sheep red blood cell antibodies, serum immunoglobulin levels, spleen and thymus weights, hematocrits, and leukocyte differential counts on peripheral blood. No significant differences were found between test and weight-bearing, harnessed controls; however, the thymuses of animals in both these groups were significantly smaller than untreated cage controls. The lack of an effect of simulated weightlessness on the immune system is an interesting result, and its significance is discussed.

Caren, L. D.↗

Specific immunization of mice against Leishmania mexicana amazonensis using solubilized promastigotes

In this work, it was demonstrated that mice (BALB/c strain) highly susceptible to Leishmania mexicana amazonensis can be protected against infection by this parasite by being preimmunized with whole solubilized (in a buffer that contained EDTA, NP-40, and SDS) promastigotes; the use of adjuvant or intact inactivated parasite cells is shown to be not necessary. The best immunization schedule consisted of three intravenous injections of 5 x 10 to the 7th parasite equivalents, administered one to eight weeks before infection. Immunized mice exhibited a marked inhibition of primary lesion development, reduced numbers of parasites in the spleen, and reduced death rate.

Barral-Netto, M.↗

Cytokines and immune surveillance in humans

Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to further explore the effects of space flight on cytokines and cytokine-directed immunological function.

Sonnenfeld, Gerald↗

Cytokines and immune surveillance in humans

Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

Sonnenfeld, Gerald↗

Immune changes in humans concomitant with space flights of up to 10 days duration

The time relation of various classes of in-flight human physiological changes is illustrated. Certain problems, such as neurovestibular, fluid, and electrolyte imbalances tend to occur early in a flight, followed by stabilization at some microgravity equilibrium level. Cardiovascular dysfunctions and erythrocyte mass losses appear to follow a similar pattern, although the significant changes occur later in flight. Bone and calcium changes and radiation effects are thought to progressively worsen with time, whereas the time course of immune change is yet to be fully understood. Significant immunologic changes in cosmonauts and astronauts during and after space flight have been documented as have microbiological changes. Thus, space flight can be expected to effect a blunting of the human cellular immune mechanism concomitant with a relative increase in potentially pathogenic microorganisms. This combination would seem to increase the probability of infectious disease events in flight.

Taylor, Gerald R.↗

Portable Immune-Assessment System

Portable immune-assessment system developed for use in rapidly identifying infections or contaminated environment. System combines few specific fluorescent reagents for identifying immune-cell dysfunction, toxic substances, buildup of microbial antigens or microbial growth, and potential identification of pathogenic microorganisms using fluorescent microplate reader linked to laptop computer. By using few specific dyes for cell metabolism, DNA/RNA conjugation, specific enzyme activity, or cell constituents, one makes immediate, onsite determination of person's health or of contamination of environment.

Pierson, Duane L.↗

Role of Dendritic Cells in Immune Dysfunction

The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

Savary, Cherylyn A.↗

The Influence of Modulated Signal Risetime in Flight Electronics Radiated Immunity Testing with a Mode-Stirred Chamber

For electromagnetic immunity testing of an electronic system, it is desirable to demonstrate its functional integrity when exposed to the full range and intensity of environmental electromagnetic threats that may be encountered over its operational life. As part of this, it is necessary to show proper system operation when exposed to representative threat signal modulations. Modulated signal transition time is easily overlooked, but can be highly significant to system susceptibility. Radiated electromagnetic field immunity testing is increasingly being performed in Mode Stirred Chambers. Because the peak field vs. time relationship is affected by the operation of a reverberating room, it is important to understand how the room may influence any input signal modulation characteristics. This paper will provide insight into the field intensity vs. time relationship within the test environment of a mode stirred chamber. An understanding of this relationship is important to EMC engineers in determining what input signal modulation characteristics will be transferred to the equipment under test. References will be given for the development of this topic, and experimental data will be presented

Ely, Jay J.↗

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↗

Immune alterations in male and female mice after 2-deoxy-D-glucose administration

Administration of 2-deoxy-D-glucose (2-DG) induces acute cellular glucoprivation. In the current study, we examined differences in immune parameters after 2-DG administration in both sexes. Male and female BDF1 mice were injected three times, 48 h apart, either with a saline solution (control group) or with 2-DG in saline (500 mg/kg). Two hours after the last injection, blood and spleens were collected. Plasma levels of interleukin-1beta, and interferon-gamma levels were measured. Additionally, the levels of the specific leukocyte antigens CD3, CD4, CD8, T cell receptor (TCR) alpha/beta, I-Ad, and H-2Ld/H-2Db were evaluated by flow cytometry on both blood and spleen cells. The blastogenic response of leukocytes from both tissues to mitogens was assessed. Levels of glucose, corticosterone, testosterone, progesterone, 17beta-estradiol, follicle-stimulating hormone, and luteinizing hormone were also determined. Increases in the percentage of cells bearing TCR alpha/beta and I-Ad in the blood and H-2Ld/H-2Db in the spleen were observed in the 2-DG-treated group for both sexes. In contrast, higher corticosterone and IL-1beta plasma concentrations, as well as higher percentages of splenocytes bearing TCR alpha/beta and I-Ad, and lower mitogen-induced proliferation of mature T splenocytes (79%) were observed in female but not in male mice injected with 2-DG compared with those injected with saline (p < 0.05). Taken together, these results suggest that female mice are more sensitive than male mice to immune alterations induced by 2-DG administration.

Non-NASA Center↗

Immune responses in humans after 60 days of confinement

A confinement experiment in a normobaric diving chamber was undertaken to better understand the effect of confinement and isolation on human psychology and physiology. Pre- and postconfinement blood samples were obtained from four test subjects and control donors to analyze immune responses. No modification in the levels of CD2+, CD3+, CD4+, CD8+, CD19+, and CD56+ cells was observed after confinement. Mitogen-induced T-lymphocyte proliferation and interleukin-2 receptor expression were not altered significantly. Whole blood interferon-alpha and gamma-induction and plasma cortisol levels were also unchanged, as was natural killer cell activity. These data suggest that in humans, no specific components of the immune response are affected by a 2-month isolation and confinement of a small group.

NASA Discipline Number 18-10↗

Human Immune Function and Microbial Pathogenesis in Human Spaceflight

This oral presentation was requested by Conference conveners. The requested subject is microbial risk assessment considering changes in the human immune system during flight and microbial diversity of environmental samples aboard the International Space Station (ISS). The presentation will begin with an introduction discussing the goals and limitations of microbial risk assessment during flight. The main portion of the presentation will include changes in the immune system that have been published, historical data from microbial analyses, and initial modeling of the environmental flora aboard ISS. The presentation will conclude with future goals and techniques to enhance our ability to perform microbial risk assessment on long duration missions.

Pierson, Duane J.↗

Immune Dysregulation Following Short versus Long Duration Space Flight

Immune system dysregulation has been demonstrated to occur during spaceflight and has the potential to cause serious health risks to crewmembers participating in exploration-class missions. A comprehensive immune assessment was recently performed on 13 short duration Space Shuttle crewmembers and 8 long duration International Space Station (ISS) crewmembers. Statistically significant post-flight phenotype alterations (as compared to pre-flight baseline) for the Shuttle crewmembers included: granulocytosis, increased percentage of B cells, reduced percentage of NK cells, elevated CD4/CD8 ratio, elevated levels of memory CD4+ T cells, and a CD8+ T cell shift to a less differentiated state. For the Shuttle crewmembers, T cell function was surprisingly elevated post-flight, among both the CD4+ and CD8+ subsets. This is likely an acute stress response in less-deconditioned crewmembers. The percentage of CD4+/IL-2+, CD4+/IFNg+ and CD8+/IFNg+ T cells were all decreased at landing. Culture secreted IFNg production was significantly decreased at landing, whereas production of Th2 cytokines was largely unchanged. It was found that the IFNg:IL-10 ratio was obviously declined in the Shuttle crewmembers immediately post-flight. A similar pattern of alterations were observed for the long duration ISS crewmembers. In contrast to Shuttle crewmembers, the ISS crewmembers demonstrated a dramatic reduction in T cell function immediately post-flight. This may be related to the effect of acute landing stress in conjunction with prolonged deconditioning associated with extended flight. The reduction in IFNg:IL-10 ratio (Th2 shift) was also observed post-flight in the ISS crewmembers to a much higher degree. These data indicate consistent peripheral phenotype changes and altered cytokine production profiles occur following space travel of both short and long duration.

Crucian, Brian E.↗

CHOICE - Directed Study: Consequences of longterm- Confinement and Hypobaric HypOxia on Immunity in the Antarctic Concordia Environment

Concerning ground-based space physiological research, the choice of analog must carefully match the system of interest. For spaceflight-associated immune dysregulation (SAID), Antarctica winter-over has emerged as potentially the best terrestrial analog. The prolonged mission durations, extreme/dangerous environment, station-based lifestyle, isolation from outside world, disrupted circadian rhythms, and other psychological aspects make this analog extremely high fidelity for exploration-class space missions (long duration lunar, Mars). NASA, ESA and RSA are currently investigating SAID, with NASA currently operating the Integrated Immune flight study. It is desirable to have a ground analog for SAID validated, so that potential countermeasures might be validated terrestrially prior to during flight. For this presentation, NASA data collected on the winterover 2009 crewmembers, baseline through early deployment will be presented. Through early deployment (approximately 2-3 weeks at Concordia), phenotypic alterations included increased levels of memory T cells, shifts among the CD8+ T cell compartment to a more mature phenotype, and increases in constitutively activated T cells. CD8+/IFNg+ T cell percentages, and T cell blastogenesis functional responses were depressed early deployment as compared to healthy controls. In four compatible subjects, secreted T cell Th1/Th2 cytokines were measured following culture stimulation, and a Th2 shift was observed as compared to controls. Post-winter over frozen sample return will be required to determine if this shift persisted during the winter over period. Additionally, circadian rhythms remained altered compared to baseline, as determined through 5x daily cortisol measurements. Latent viral reactivation will not be determined until frozen sample return occurs.

Sams, Clarence↗

Immune System Dysregulation, Viral Reactivation and Stress During Short-Duration Spaceflight

The objective of this NASA Short-Duration Bioastronautics Investigation (SDBI) was to assess spaceflight-associated immune dysregulation. Many previous studies have investigated this phenomenon post-flight, and found altered distribution and function of the peripheral leukocyte populations. Alterations in cytokine production profiles have also been reported. Unfortunately, post-flight data may be altered by the stress associated with high-G re-entry and readaptation to unit gravity following deconditioning. Therefore, the current study collected blood and saliva samples from crewmembers immediately before landing, and returned those samples to Earth for terrestrial analysis. Assays include peripheral comprehensive immunophenotype, T cell function, cytokine profiles, viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. A total of 18 short duration crewmembers completed the study and the final data will be presented.

Pierson, Duane↗