The Immune System and Microgravity. Overview in Humans. Innate Immunity

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1 The Immune System and Microgravity Dr. Patricia C. Hunt DO, MHA, CHCQM Overview in Humans There are two types of immune response: innate immunity First line of defense when a microbe enters the body. Rapid response of macrophages, neutrophils Mirrored in Drosophila: hemacytes adaptive immunity Memory response Antibody production Innate Immunity Nonspecific First line of defense against foreign pathogens mediated by natural killer (NK) cells, macrophages, neutrophils, basophils, eosinophils and mast cells. Macrophages and mast cells serve as sentinels stationed in tissues, which continuously monitor their microenvironment for signs of distress. How does it work? Identification of foreign invaders in the bodythis is called recognizing self from non-self. They have the ability to communicate through chemical signals (cytokines, hormones) and by cell to-cell contact (surface receptors). R-1

2 Immune Cell Communication Adaptive Immunity A macrophage traps a foreign bacteria/virus. It processes the foreign organism and becomes an antigen presenting cell (APC). The APC then presents the processed foreign invader to a Helper T cell. T cell activation and undergoes clonal expansion. Memory Helper T cells will remember the target. It causes the B cell to become a plasma cell that makes specific antibody against the invader. The antibodies attach to the virus to destroy it. The B cell clonally expands to make Memory B cells. What do we currently know occurs with prolonged space flight? Hypoplasia of lymphoid organs, alterations of mitogen-induced blastogenesis of leukocytes Severe production of interferons Development of bacterial, viral infections during flight mission, or first week after recovery. (flu, p. aeruginosa, beta strep) Impaired wound healing Impaired T cell activation Aging? Autoimmunity? Autoimmunity R-2

3 Fun (Aerospace)Facts about the Space Station 14th anniversary of continuous human occupation on Nov. 2, million lines of software code on the ground support 1.8 million lines of flight software code. Eight miles of wire connects the electrical power system. The 75 to 90 kilowatts of power for the ISS is supplied by an acre of solar panels. But wait, there s more.. The ISS solar array surface area could cover the U.S. Senate Chamber three times ISS has an internal pressurized volume of 32,333 cubic feet, or equal that of a Boeing 747. The solar array wingspan (240 feet) is longer than that of a Boeing /300 model, which is 212 feet. Fifty-two computers control the systems on the ISS. radiation, microbes, stress, Immune Dysregulation altered sleep cycles and isolation microgravity Rat Leukocytes, Mussel Hemacytes, oh, my! TripleLux-A will test leukocytes in rats on the space station. TripleLux-B will explore how microgravity causes changes in cellular-level genetic mechanisms, including DNA repair. It will compare microgravityinduced changes in rat leukocytes with similar immune system cells in blue mussels. These mussel and rat cells are considered model organisms; they have characteristics making them easy to maintain, reproduce and study in a laboratory. The mussels, for example, generate large numbers of immune system cells that are easy to collect without harming the animal. What do we hope to learn? The aim of Triplelux-A is to understand the mechanisms at the cellular level which underlie Impairment of immune functions under spaceflight conditions, AND Clearly separate the effects of microgravity from other spaceflight factors by use of an onboard 1g centrifuge. Specifically, the ability of rat macrophages to phagocytize zymosan (as an analogue of bacteria) is assessed. Phagocytosis is quantified using luminol as a detector for reactive oxygen species (burst) produced during phagocytosis of zymosan, a safe bacterial substitute. What do we hope to learn? TripleLux-B launched to the International Space Station in December 2014 on Space X s fifth resupply mission. In February 2015, TripleLux-A was scheduled to follow aboard SpaceX's sixth mission. Both investigations examine cellular changes in the immune system and separate out the specific effects of microgravity from other spaceflight factors like radiation, microgravity, and physiological stressors -- confinement, isolation, disrupted circadian rhythms. R-3

4 The Gene, Immune and Cellular Responses to Single and Combined Space Flight Conditions - B (TripleLux-B) compares the mechanisms of vertebrate and invertebrate cells which become impaired through induction of gene activation, phagocytosis, and DNA repair in vertebrate and invertebrate immune cells. TripleLux-B examines the immune function of Mytilus edulis, the blue mussel, hemacytes, compared to rodent macrophages to function in microgravity. Tools for Testing A safe substitute for bacteria, zymosan, is tagged with Luminol to detect oxygen bursts which immune cells induce to fight infectious agents. To clarify if microgravity, radiation, or both is responsible for changes in the immune response, cells will be exposed to microgravity, simulated Earth gravity, and a control on Earth. Is our cellular machinery is able to work without gravitational force or will our cellular architecture keep us dependent on Earth s gravity? To clarify whether microgravity, radiation or a combination is responsible for immune system changes during spaceflight, researchers will expose the cells to microgravity and simulated Earth gravity. The latter will be created in the European Space Agency s BIOLAB centrifuge. Data from these conditions will be compared with measurements of accumulated radiation doses from a reference experiment on the ground. Researchers will assess whether microgravity and radiation work together to create a stronger effect. (This investigation must be performed aboard the space station because cosmic radiation cannot be simulated on Earth.) Credits and Thanks NASA on the web, and personal communications. Dr. Stanley Simon, DO Professor of Allergy and Immunology, NYIT-COM R-4

5 A Tribute to other divisions Occupational Medicine Preventive Medicine R-5