4.3. Autoimmunity in the brain: Multiple sclerosis
It is known that deregulation of the immune system plays a crucial role in neurological disorders. This is particularly evident in diseases where the underlying pathology is autoimmune-related. MS is a chronic autoimmune disease in which self-reactive T cell clones attack the myelin component of the CNS. In early MS, active lesions are characterized by focal demyelination of white matter accompanied by perivenular infiltrates of immune cells such as CD8+ T cells, CD20+ B cells, plasmablasts, and macrophages that form a typical perivascular cuff. This demyelination disrupts the BBB and causes progressive loss of neurological function due to damage to the myelin sheath around the neuronal axons (Frischer et al., 2009).
Genetic predisposition to MS is linked to specific HLA class II haplotypes (HLA-DR15 and HLA-DQ6), which are thought to present autoantigens to the adaptive immune system. Other immune-related genes have also been implicated in the development of MS, such as those encoding for IL-17 and IL-2. In addition to genetics, various environmental factors, such as lifestyle, vitamin deficiencies, and infections such as EBV, have been identified as risk factors for MS. Studying the immune response in the experimental autoimmune encephalomyelitis (EAE) model has provided insight into the role of T cell phenotypes and their effector mechanisms in the pathology of MS (Pilli, Zou, Tea, Dale & Brilot, 2017).