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The human immune system is composed of a complex set of specialized cells, chemicals, and organ systems that interact to protect the host from pathogenic challenge and aberrant tissue growth. The immune system consists of two major elements: innate immunity and acquired immunity. The innate or nonspecific immunity includes the phagocytes and natural killer cells as well as chemical factors (lysozyme, complement, etc.) that act to control extra-cellular pathogens. Resistance of this system to pathogenic entities is not adaptive and is not increased by repeated exposure. The acquired immune system itself consists of two functional components: humoral immunity and cell-mediated immunity. These elements adapt and become more responsive with repeated exposure to pathogens. Simplistically, the humoral immune system encompasses protein factors (antibodies) that bind and neutralize their antigen targets and the specific cells (B cells) that produce the antibodies. The cell-mediated immune system includes the T cells which regulate many aspects of overall immune response and directly provide self vs. non-self discrimination. This system is critical to the control of intracellular pathogens (such as viruses) and the containment and elimination of malignant cells. These elements interact to protect the host from a broad range of medical threats. Defects in immune function can result in three distinct failure modes: (1) immunodeficiency, where the immune system fails to contain infections, (2) autoimmunity, an inappropriate response to self antigens that damages the host, and (3) hypersensitivity, an over-reaction of the immune system to innocuous foreign antigens. Any of these failures can have a significant medical impact on crewmembers during space flight. Precise regulation of immune function is critical because an overly active immune system can be just as damaging as an unresponsive one. Finally, the interplay of immune changes and environmental exposures in space flight (e.g., radiation, chemical exposures) can also induce long-term health risks for the crewmember. [ABSTRACT FROM AUTHOR]