Myelin is expressed in the circulation, and other CNS antigens are thought to be expressed in the cervical lymph nodes, which can trigger the conversion of autoaggressive myelinreactive T cells to pathogenic T cells. Adhesion molecules, the integrins, allow these myelin-reactive T cells to penetrate the blood-brain barrier (BBB) under inflammatory conditions, and in this way, activated and memory T cells can enter the CNS [57] . Autoaggressive myelin-reactive T cells migrate into the CNS, where they recognize their cognate target antigens, and the movement of antigen-presenting cells (APCs) into the CNS is essential for lymphocyte reactivation within the CNS compartment and the initiation of the inflammatory cascade in the development of EAE [58] . Subsequently, inflammatory and immune cells, such as granulocytes and macrophages, are attracted into the CNS parenchyma, where they mediate tissue inflammation, leading to demyelination and tissue damage [59] . The brain was formerly considered an immunoprivileged organ, but this perspective has been revised in the last two decades [60] . Today, we understand that any damage to the CNS can activate immune cells in situ in the CNS, particularly microglial cells. Deshpande et al. demonstrated the transient inactivation of microglial cells via a cell-specific deficiency of CD40 expression, indicating that microglial cells are crucial for maintaining the autoimmune responses in the CNS [61] . The major histocompatibility complex (MHC, also known as "human leukocyte antigens" in humans) class II molecules are only displayed on specialized APCs (e.g., dendritic cells [DCs], B cells, and macrophages), whereas MHC class I molecules are expressed by all cells in the inflammatory milieu of the CNS [62] . Microglial cells upregulate the expression of MHC and costimulatory molecules to initiate the generation and maintenance of the inflammatory milieu. DCs seem to play a critical role in antigen presentation to invading T cells and in the release of cytokines and chemokines, thereby guiding the entry of monocytes, lymphocytes, and cells with a phenotype similar to that of DCs into the lesion [63] .