References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 77 Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89 XI 1 Introduction 1.1 Antigen Presentation and Antigen Presenting Cells A key issue in the pathogenesis of any chronic degenerative (auto )immune disease of the central nervous system (CNS) is how pathologically altered autologous neuronal proteins can trigger a reaction of the immune system. The specific and greatly multi plied immune response is decisive for the outcome of the disease. Current knowledge shows that the immune system gets involved and potentiates a progressive neuronal degeneration in two ways, which are not mutually exclusive. First, provided the immunogenic autologous protein occurs in the interstitial fluid of CNS in amounts which cannot be phagocytized and cleared by the leptomeningeal macrophages, it reaches the cervical lymph nodes passively along the perivascular spaces, the cerebrospinal fluid compartment above the cribriform plate, and the lymphatics of the nasal mucosa (Cserr and Ostrach 1974; Weller et al. 1992; Zhang et al. 1992; Kida et al. 1993). The immunological significance of this "late" pathway typical for advanced neurodegeneration has been confirmed by Harling-Berg et al. (1989), who showed that the cervical lymph nodes are the main site of antibody production against foreign protein injected into the central gray matter of the rat brain."

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