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.