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AG Immunzelldynamik

Laufzeit: 01.01.2010 - 31.12.2014

Kurzfassung


The immune system is in its physiology is one of the most dynamic aspects of the body. The various cells of the immune system are responsible for the integrity of the body, for the rapid discharge or destruction of pathogens, for the tolerance of commensals and for the destruction of degenerate or virus-infected body cells. If, however, a malfunction in these highly specialized processes arises, autoimmunity can form. The immune cells are transported in the bloodstream / lymph between organs,...The immune system is in its physiology is one of the most dynamic aspects of the body. The various cells of the immune system are responsible for the integrity of the body, for the rapid discharge or destruction of pathogens, for the tolerance of commensals and for the destruction of degenerate or virus-infected body cells. If, however, a malfunction in these highly specialized processes arises, autoimmunity can form. The immune cells are transported in the bloodstream / lymph between organs, but travel great distances within the organs that their small size belies. Only since the recent introduction of two-photon microscopy is the applied research methodology possible, which allows for the these processes to be studied in living tissue. In contrast to the snapshot offered by the conventional process of histology, the two-photon microscope can record actions and interactions of immune cells in tissue and organ structures in living, anesthetized animals over a period of up to 12 hours. This is a fluorescence-based method which allows cells several hundred microns deep in the tissue to be visible. This can be used in target organs of inflammation - in our case, the brain and spinal cord - the development of lesions and the relevant mechanisms involved in this directly.
Misguided immune responses lead to damage of certain areas. In the case of the central nervous system, it usually leads to the demyelinating disease, multiple sclerosis (MS). MS is the most common chronic inflammatory disease of the central nervous system (CNS), which can begin in young adulthood (between 20 and 40) and leads to early disability and premature retirement. In Germany the number of sufferers is estimated at about 140,000. So far, the identification of the exact causes and triggers of the development of multiple sclerosis are being researched. In addition, the currently approved treatment options are inadequatly effective. Therefore, a concern of our basic research are the questions about how the etiological basis is to be better clarified in order to develop new specific therapeutic approaches. For a detailed study of neurological and immunological basis for investigation and validation of new therapeutic approaches, the animal model of MS, experimental autoimmune encephalomyelitis (EAE) is necessary. We use intravital microscopy to study the formation of demyelinating lesions in the animal model of MS. The focus is the study of interactions of immune cells (T cells, dendritic cells, macrophages) to the target organ cells (neurons, oligodendrocytes, microglia). We have developed special surgical techniques to allow us to monitor the inflammation in the brain stem and in mouse brains.
References

Siffrin, V, Radbruch H, Glumm R, Niesner R, Paterka M, Herz J, Leuenberger T, Lehmann SM, Luenstedt S, Rinnenthal JL, Laube G, Luche H, Lehnardt S, Fehling H, Griesbeck O, Zipp F (2010) In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 33: 424-436.
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