Page 154 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Space travel and microgravity effects on immune cell function are highly cell-type specific.
Evidence that the immunosuppressive effects of space travel in general and microgravity, in particular, can be attributed to specific cell-autonomous mechanisms which impact on different compartments of the immune system, has over the past three decades slowly become more-and-more evident. Advancement in this field has been slow due to the apparent lack of experimental opportunities and the technical difficulties in the analysis of scientific work on the immune system in microgravity. The notion, however, that space travel in general and microgravity, in particular, are immunosuppressive was much fostered by the observation that Con-A stimulation of T cell compartment resulted in reduced mitogenic responses in this cell type under microgravity. Thus a lot of attention has been focused on this branch of immunity. Typically studies show that cell division is reduced between 50–89% at 0×g when compared to 1×g controls either in space or during simulated microgravity[22].A variety of studies indicates that microgravity interferes with the functionality of the NK cell compartment. NK cells isolated from astronauts are deficient in target cell killing in ex vivo assays (hence out of the context of a possible immunosuppressive cytokine milieu, suggesting that cellular factors are essential here)[15]. Although not well studied, maturation of dendritic cells, significant for the instruction of T cells in adaptive immunity is somewhat impaired under gravity[62]. In contrast neutrophil action seems to be enhanced under microgravity. Cosmonauts spending 1 to 22 months in microgravity (occupants of the Russian Mir space station) display increased granulocyte superoxide production and enhanced levels of surrogate markers for such increased granulocyte activity like elevated erythrocyte superoxide dismutase activity and glutathione oxidation[25]. Hence, if anything, immunity in the neutrophil compartment is slightly stimulated rather than inhibited by microgravity. The notion that space travel can specifically interfere with individual branches of protection without negatively influencing granulocyte immunology adds to the interest that identifying the molecular targets of microgravity may have. Evidence that defects in innate immunity contribute to the pathogenesis of the autoimmune disease is rapidly accumulating[63]. Recent genome-wide associations studies (GW AS) have been instrumental in identifying novel genetic risk factors predisposing to Crohn’s disease and many of the alleles involved confer reduced activity in the innate immune system [36]. In line with these genetic studies, patients with autoimmune disease were shown to exhibit diminished innate immunity as compared to healthy individuals[35] and genetic deficiencies in neutrophil function are highly similar to and clinically even
Chapter 7
Chapter 7
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