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uni'wissen 01-2012_ENG

Whereas the identification of the calcium channel goes back to research in Freiburg in the 1990s, up until now only little was known about the role of the channel for cytotoxicity. “We developed tests a while back in order to measure this toxicity in a quick and simple way. In examining the ­patients, we found out that the cytotoxicity does not function without the calcium channel and that this prevents viral infections from being controlled.” The diagnostic methods derived from these ­experiments can be transferred to other groups of immune defects. The scientists are considering the prospect of using their new findings for thera­ pies. In the case that the T cells exhibit overac­ tive behavior and threaten to lead to the rejection of a transplant, an obstruction of the calcium ­influx could slow down the activation signal. “It could be advantageous to block the T cells in certain cases instead of using imprecise medi­ cines that suppress an immune response, for ­instance in autoimmune diseases like multiple sclerosis,” says Ehl. Learning to Understand the Disturbed Development As head of the Section for Pediatric Immunology at the CCI’s Center for Pediatrics and Adoles­ cent Medicine, Ehl founded a reference center for defects of the immune system that is now recog­ nized throughout Europe. His focus is on study­ ing the immune response of the T cells. In addition to conducting important research on this topic, he has initiated a study on the treat­ ment of combined immunodeficiencies at the center. “We want to improve the treatment of ­patients by learning to better understand the As with many genetic diseases, SCID occurs more frequently in children who are the product of marriages between relatives. In such cases, genetically based immunodeficiencies are trans­ mitted twice. “It can also happen with parents who are not related, but the probability is lower,” says Ehl. In general, lymphocytes play the main role in the immune system’s answer to a germ. They include the so-called T cells, precursor cells from the bone marrow that penetrate into the thymus gland, where they are shaped further and prepared for their task. As soon as the body gives the signal that it is ready, the T cells begin circulating in the blood and are ready to destroy invaders that can cause an illness. The B cells have the same task. They also develop out of precursor cells in the bone marrow and are pre­ pared for their function in the immune defense. In the case of SCID, it can happen that only very few of these two types of immune cell are avail­ able or that the cells are formed but cannot be activated due to a defect in function. Freiburg doctors were among the first to conduct research into the causes for this failure. Immune Cells Do Not Work as Planned “Cellular processes play an important role,” says Ehl. The T cell receives an activation signal from a T cell receptor, which sits on the cell like a tentacle. A calcium channel in the membrane surrounding the cell is then opened, allowing positively charged ions to flow into the cell. The calcium ions function as a second messenger that activates the switching points in the cell. The cell divides and forms messengers to destroy tumor cells and cells infected by the virus. For example, it punctures holes in the membrane of such target cells, thus demonstrating its cyto­ toxicity. In one form of SCID the problem stems from a calcium channel. A mutated gene ­prevents the channel from functioning as it is supposed to and the T cell from being activated. “We have succeeded in understanding why the immune cells, although they are there, do not work as the are supposed to,” says Ehl. “The ­difficult ­research on rare diseases is especially useful for learning about how the immune ­system works in general.” The smaller, green-bordered T cell attaches itself to the larger infected target cell in order to destroy it. Freiburg scientists are studying why this defensive ­reaction no longer functions in some patients. 10