Figure 16.

Schematic overview of immune processes in the EAE model. (a) Autoreactive CD4$+$ T cells that have been activated in peripheral lymphoid organs by the injection of antigen-adjuvant emulsion infiltrate the CNS via passage through the blood–brain barrier. This passage is mediated by interaction adhesion molecules, such as the $\mathit{\alpha }$4$\mathit{\beta }$1-integrin VLA-4 with ICAM-1 on blood–brain barrier endothelial cells (see insert). By local cognate interactions with local antigen-presenting cells, including dendritic cells, macrophages and microglia, the T cells elicit a cascade of pathophysiological reactions leading to inflammation and demyelination. (b) A second infiltrating lymphocyte type is the B cell, which secrete antibodies that, via binding to myelin sheaths and oligodendrocytes, elicit macrophage-mediated and complement-dependent cytotoxicity (ADCC and CDC, respectively). However, this classical role of B cells requires adjustment, because B cells have a much more elaborate pathogenic role. (c) The target of the autoimmune process is the axon–myelin unit, which comprises axons, the enwrapping myelin sheaths and the myelin-forming oligodendrocytes. In the healthy CNS, damaged oligodendrocytes can be replaced by infiltrating oligodendrocyte precursor cells (OPCs), but this repair capacity seems impaired in MS.