麻豆淫院

(麻豆淫院Org.com) -- In April 2010, personnel aboard the International Space Station plan to carry out an experiment designed by a San Francisco VA Medical Center researcher that will investigate why the immune system鈥檚 T cells stop working in the absence of gravity. The experiment has implications for understanding the body鈥檚 ability to mount an immune response on earth, as well.

On earth, T cells - white blood cells that are essential for proper immune function - stop functioning in people with untreated HIV/AIDS, as well as in some elderly people, leading to the development of potentially fatal opportunistic infections.

The experiment aboard the ISS is meant to shed light on the genetic mechanisms behind T cell shutdown, according to principal investigator Millie Hughes-Fulford, PhD, director of the Laboratory for Cell Growth at SFVAMC and an astronaut who flew aboard the space shuttle in 1991.

鈥淔rom the beginning of the U.S. Apollo moon program, we鈥檝e known that about half of our astronauts develop suppressed immune systems, either during flight or shortly afterwards, and we have since learned that non-functioning T cells are at least partly responsible,鈥� says Hughes-Fulford, who is also a professor of medicine at the University of California, San Francisco.

鈥淚f we can get to the root cause, we can potentially help older people, people with HIV/AIDS, and anyone else who is immunocompromised here on earth,鈥� she says. 鈥淲e will also overcome a serious obstacle to long-term space exploration. A runaway infection among the crew due to compromised immune systems would mean disaster for a multi-year Mars mission, for example.鈥�

Normally, Hughes-Fulford explains, the immune system responds within four hours of exposure to an infectious agent by expressing certain genes. This gene expression, in turn, initiates a series of molecular and cellular reactions that ultimately result in the activation of T cells and other white blood cells, which then migrate to the site of the infection.

In previous experiments with human cell cultures aboard the ISS, Hughes-Fulford found that a group of 47 genes associated with T-cell activation are not expressed in the absence of gravity. 鈥淣ow we鈥檙e taking this research one step further by investigating this phenomenon in live mice on the space station, outside of earth鈥檚 gravity field,鈥� she says. 鈥淲e hope this will allow us to pare down our list of non-expressing genes to a much smaller number of genes, and give us a better handle on what鈥檚 happening in humans.鈥�

Hughes-Fulford notes that even though mice have far fewer genes in total than humans, mouse genetics and human genetics have proven to be 鈥渧ery much the same鈥� in terms of immune response.

Shuttle flight STS-131, currently scheduled for lift off on April 5, 2010, will deliver two self-contained experimental rodent habitats called Animal Enclosure Modules to the space station. Each module will contain one half of Hughes-Fulford鈥檚 two-part experiment.

In part one, mice with so-called na膹ve T cells - cells that have not previously been exposed to an infectious agent - will live aboard the ISS without gravity, while a matched group of control mice live on earth under normal gravity. After the experimental mice return to earth aboard the shuttle, both groups of mice will be exposed to OVA, a protein found in egg white that functions as a model of infection. The expectation is that the T cells in the experimental mice will not activate, while the T cells in the control mice will. Hughes-Fulford and the rest of her team will compare gene scans for the two groups of mice to see which genes do not express in the experimental animals.

Part two of the experiment will use orbital experimental mice and earth-bound control mice to compare the reactions of memory T cells, which are T cells that have already been exposed to a disease agent - or, in this case, OVA - when they are exposed to OVA a second time. As in part one, the expectation is that the memory T cells in the orbital mice will not activate. Comparative gene scans will reveal which genes do not express in those mice.

Hughes-Fulford explains that memory T cells react much more quickly and effectively than na膹ve T cells in the presence of the disease agent to which they have been exposed, which is what gives vaccinations their protective effect. 鈥淲e鈥檙e doing this experiment because there is evidence that memory T cells don鈥檛 work in microgravity,鈥� she says. 鈥淎pparently, some astronauts are not protected against diseases they have been inoculated for. And we want to find out why.鈥�

Hughes-Fulford, who was a payload specialist aboard shuttle flight STS-40 in 1991, says the ultimate goal of her experiment is to point the way toward gene therapy for people with non-functioning immune systems. 鈥淚f we can find which molecules are regulating the expression of these key genes, we could theoretically take those molecules, put them into cells, and turn on genes that are not expressing.鈥�

She cautions that such therapy is 鈥渕any, many years away.鈥� At this stage, 鈥淲e鈥檙e just laying the groundwork. At the same, time, we鈥檙e uncovering fundamental mechanisms that control the immune system, and what happens to those mechanisms when you remove them from the gravity field in which they evolved.鈥�