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Hazards of Lunar Surface Exploration: Determining the Immunogenicity/Allergenicity of Lunar Dust

Although infrequent, there have been Apollo program reports of lunar dust (LD) exposure leading to notable upper respiratory symptoms in select crewmembers. Possible mechanisms include particulate irritation, oxidization and release of noxious gas, or legitimate adaptive immune-mediated response. Although sterile non-protein matter would not be expected to be an allergen, one Apollo flight surgeon reported increasing symptoms upon repeated exposure with associated eosinophilia, indicative of allergy (*Acta Astronautica. 2008 63 (7–10): 980–987). Many ISS crews display a pattern of persistent immune system dysregulation and latent virus reactivation (NPJ Microgravity. 2015 Sep 3; 1:15013; NPJ Microgravity. 2017 Apr 12; 3:11). Some ISS crews manifest atypical respiratory and/or dermatitis symptoms which could have an allergic pathogenesis (J Allergy Clin. Immunol. Pract. 2016 Jul-Aug; 4(4):759-762.e8). It is logical to anticipate crew immune dysregulation would worsen during prolonged deep space missions. Planetary surface hazards will only complicate crew health risks. This study with investigate if LD exposure will elicit an IgE mediated allergic response either to the LD itself or concomitant antigen exposure during spaceflight. Allergic reactivity could adversely increase clinical and operational impacts for long-duration lunar astronauts and affect countermeasure requirements for surface vehicles. Specific aims for this study are to answer two questions: (1) Does in vitro LD exposure result in increased histamine from human peripheral blood basophils? (2) Can LD impact the capacity of CD4+ T helper and/or CD19+ B-cell mediated IgE production? To address these questions, after the proposal and selection by NASA, our laboratory has separately requested and been approved for receipt of actual LD samples from the Apollo 16 mission. These samples will be used during the study to complete the proposed set of in vitro cell culture experiments (short and long term), using human peripheral blood mononuclear cells (PBMC) and basophils from both atopic and non-atopic individuals. Cells will be co-cultured with cellular mitogens, common recall antigens (Der p1), fine ground silica quartz (as a possible allergenic component of LD), or LD, to study whether LD exposure for varying time intervals will alter the generation of selective immune responses associated with clinical allergic reactions. Measured outputs include supernatant-derived IgE, tryptase, histamine, and selected cytokine levels. Cellular activation will be monitored by assessing activation markers via flow cytometry. EM/x-ray analysis will be used to determine cellular interactions with dust particles. A series of validation experiments was initiated in FY22 once the delivery of LD was received. Based on initial experimental findings, we are optimizing the culture conditions, LD concentrations, and refining our other protocol stimuli.

immunology↗

NASA NTRS1999

Sustained Partial Sleep Deprivation: Effects on Immune Modulation and Growth Factors

The vulnerability to medical emergencies is greatest in space where there are real limits to the availability or effectiveness of ground based assistance. Moreover, astronaut safety and health maintenance will be of increasing importance as we venture out into space for extended periods of time. It is therefore critical to understand the mechanisms of the regulatory physiology of homeostatic systems (sleep, circadian, neuroendocrine, fluid and nutritional balance) and the key roles played in adaptation. This synergy project has combined aims of the "Human Performance Factors, Sleep and Chronobiology Team"; the "Immunology, Infection and Hematology Team"; and the "Muscle Alterations and Atrophy Team", to broadly address the effects of long term sleep reduction, as is frequently encountered in space exploration, on neuroendocrine, neuroimmune and circulating growth factors. Astronaut sleep is frequently curtailed to averages of between 4- 6.5 hours per night. There is evidence that this amount of sleep is inadequate for maintaining optimal daytime functioning. However, there is a lack of information concerning the effects of chronic sleep restriction, or reduction, on regulatory physiology in general, and there have been no controlled studies of the cumulative effects of chronic sleep reduction on neuroendocrine and neuroimmune parameters. This synergy project represents a pilot study designed to characterize the effects of chronic partial sleep deprivation (PSD) on neuroendocrine, neuroimmune and growth factors. This project draws its subjects from two (of 18) conditions of the larger NSBRI project, "Countermeasures to Neurobehavioral Deficits from Cumulative Partial Sleep Deprivation During Space Flight", one of the projects on the "Human Performance Factors, Sleep and Chronobiology Team ". For the purposes of this study, to investigate the effects of chronic sleep loss on neuroendocrine and neuroimmune function, we have focused on the two extreme sleep conditions from this larger study: a 4.2 hour per night condition, and a 8.2 hour per night condition. During space flight, muscle mass and bone density are reduced, apparently due to loss of GH and IGF-I, associated with microgravity. Since >70% of growth hormone (GH) is secreted at night in normal adults, we hypothesized that the chronic sleep restriction to 4 hours per night would reduce GH levels as measured in the periphery. In this synergy project, in collaboration with the "Muscle Alterations and Atrophy Team ", we are measuring insulin-like growth factor-I (IGF-I) in peripheral circulation to test the prediction that it will be reduced by chronic sleep restriction. In addition to stress modulation of immune function, recent research suggests that sleep is also involved. While we all have the common experience of being sleepy when suffering from infection, and being susceptible to infection when not getting enough sleep, the mechanisms involved in this process are not understood and until recently have gone largely overlooked. We believe that the immune function changes seen in spaceflight may also be related to the cumulative effects of sleep loss. Moreover, in space flight, the possibility of compromised immune function or of the reactivation of latent viruses are serious potential hazards for the success of long term missions. Confined living conditions, reduced sleep, altered diet and stress are all factors that may compromise immune function, thereby increasing the risks of developing and transmitting disease. Medical complications, which would not pose serious problems on earth, may be disastrous if they emerged in space.

Mullington, Janet M.↗

NASA NTRS2015

Development of Long-Lifetime Pulsed Gas Valves for Pulsed Electric Thrusters

It is advantageous for gas-fed pulsed electric thrusters to employ pulsed valves so propellant is only flowing to the device during operation. The propellant utilization of the thruster will be maximized when all the gas injected into the thruster is acted upon by the fields produced by the electrical pulse. Gas that is injected too early will diffuse away from the thruster before the electrical pulse can act to accelerate the propellant. Gas that is injected too late will miss being accelerated by the already-completed electrical pulse. As a consequence, the valve must open quickly and close equally quickly, only remaining open for a short duration. In addition, the valve must have only a small amount of volume between the sealing body and the thruster so the front and back ends of the pulse are as coincident as possible with the valve cycling, with very little latent propellant remaining in the feed lines after the valve is closed. For a real mission of interest, a pulsed thruster can be expected to pulse at least 10(exp 10) - 10(exp 11) times, setting the range for the number of times a valve must open and close. The valves described in this paper have been fabricated and tested for operation in an inductive pulsed plasma thruster (IPPT) for in-space propulsion. In general, an IPPT is an electrodeless space propulsion device where a capacitor is charged to an initial voltage and then discharged, producing a high-current pulse through a coil. The field produced by this pulse ionizes propellant, inductively driving current in a plasma located near the face of the coil. Once the plasma is formed, it can be accelerated and expelled at a high exhaust velocity by the electromagnetic Lorentz body force arising from the interaction of the induced plasma current and the magnetic field produced by the current in the coil. The valve characteristics needed for the IPPT application require a fast-acting valve capable of a minimum of 10(exp 10) valve actuation cycles. Since even 10(exp 9) cycles is well above anything demonstrated, this lower value was selected as the design point for the present work. The valve seal must remain leak-tight throughout operation, and the body must maintain a low internal leakage at relatively high operating temperatures. The full set of design requirements used for this program are summarized in Table 1. In this work, we describe two pulsed gas valves that have been fabricated to have long lifetime and demonstrate the characteristics listed above. The first is a miniaturized, conventional electromagnet-based valve while the second is a piezoelectric-based valve design. The conventional valve, shown in Fig. 1, is opened by use of a solenoid electromagnetic actuator. When current is applied to the solenoid coil, magnetic forces pull the plunger away from the valve seat, allowing fluid to flow through the valve. Removal of electrical current permits the spring and fluid pressure to seat the plunger, halting the flow of fluid. The valve body is fabricated from 304L corrosion resistant steel (CRES) and while the parts that form the magnetic circuit are fabricated from 430 CRES. This material does not have optimum magnetic properties, but its corrosion resistance permits incorporation into a design without requiring an additional plating process. A viton O-ring compound (Parker V0884-75), selected for its mechanical strength at elevated temperatures, was used for the valve seat seal. The design was based solely on the use of analytical sizing calculations, as opposed to a more rigorous finite element analysis. While this valve is small and relatively lightweight, it does not represent a design that is optimized for mass and/or a given volume envelope. The piezoelectric valve is a "puller" valve design. Applying a voltage to the piezo crystal causes it to elongate and pull a pintle off the seat, opening the valve. The valve seal consists of the pintle with an external, spherically-formed tip fabricated from Inconel 625 and the seat fabricated from Inconel 718 and possessing a spherical surface that permits the pintle to align with the valve body centerline after each cycle, maintaining the circumferential metal-on-metal seal. The contact stress on the valve pintle is expected in the worst case to be 96.5 MPa (14 ksi), which is well below the work hardening value of 413.7 MPa (60 ksi) for Inconel 615. Results presented in this work will compare the performance of each valve, both to each other and to the valve design requirements given in Table 1. In general, both valves meet all the performance envelope requirements, but the piezoelectric valve consumes considerably less power and has a faster response time over the conventional solenoid-driven valves.

Burkhardt, Wendel M.↗