Figure 1.

Demonstrated and potential mechanisms of autoimmune neuronal injury. (A) Immune attack directed against neuronal surface membrane antigens as has been shown to occur with antibodies such as anti-NMDAR. In this instance, the antibody can decrease receptor function through either (1) binding and inhibiting the receptor or (2) by cross-linking the receptors, which facilitate internalization of receptors and reduction in membrane receptor density. (B) Antibody uptake and antibody-mediated neuronal injury by antibodies directed against intracellular neuronal antigens such as anti-Yo or anti-Hu. (1) Antibody attaches to the neuronal membrane, possibly by Fc-related binding, and (2) is internalized. (3) Antibody binding to its intracellular target antigen results in neuronal injury or death. (C) Neuronal injury by T lymphocytes. Lymphocyte T cell receptors (TCRs) interact with target neurons and cause neuronal injury or death. An area of uncertainty is that mature neurons (as opposed to fetal neurons) do not express the MHC receptors normally required for T cell interaction, and the actual mechanism of neuronal recognition by T cells is undefined. (D) Possible two-step mechanism of immune attack directed against intracellular neuronal antigens. As in (B), the antibody binds to the neuronal membrane (1) followed by internalization (2) and binding to target antigens with resultant neuronal injury (3). Injured neurons upregulate MHC receptors (4) allowing recognition by cytotoxic T lymphocytes that also contribute to cell death. [Modified from Herdlevaer et al. (32)].