Immune Mediated CNS Damage英文文献.pdfVIP

Immune-Mediated CNS Damage Katrin Kierdorf, Yiner Wang, and Harald Neumann Abstract Multiple sclerosis (MS) is a demyelinating autoimmune disease. However, the persisting neurological deficits in MS patients result from acute axonal injury and chronic neurodegeneration, which are both triggered by the autoreactive immune response. Innate immunity, mainly mediated by activated microglial cells and invading macrophages, appears to contribute to chronic neurodegeneration. Activated microglia produce several reactive oxygen species and proinflammatory cytokines which affect neuronal function, integrity and survival. Adaptive immunity, particularly in cytotoxic CD8+ T cells, participates in acute demyelination and axonal injury by directly attacking oligodendrocytes and possibly neurons as well. Understanding the mechanisms of immune-mediated neuronal damage might help to design novel therapy strategies for MS. 1 Introduction Under physiological conditions, the central nervous system (CNS) is often regarded as an immune privileged organ. A coordinated immune response needs time to be established in the normal CNS parenchyma since most of the relevant molecules are not expressed and have to be induced (Lowenstein 2002). To maintain this immune compromised status, the CNS displays many structural modifications and adaptations. Firstly, a blood–brain barrier locked by endothelial tight junctions shields the CNS from invading immune cells like lymphocytes and neutrophils, and only a few transport systems allow the entrance of necessary macromolecules into the parenchyma at a minimum level (Huber et al. 2001). Secondly, there are no activated resident immune cells in the healthy CNS tissue to produce cytokines and chemokines, which can attract other immune cells to invade into the tissue parenchyma. Furthermore, H. Neumann(*), K. Kierdorf and