**4. MS and the immune system**

MS arises when there is an imbalance in the body's immune response, shifting it from a beneficial immune process that fights infection and disease towards a self-aggressive immune attack on the cells within the CNS (**Figure 1**). Genetic and environmental factor interaction may facilitate movement of autoreactive T cells, macrophages and NK cells and demyelinating antibodies from the periphery to the CNS. In the periphery self-antigens can be presented on MHC II molecules by APCs to TCRs on T cells, thereby activating proinflammatory T cells [48]. The activated T cells can then migrate through the blood brain barrier to the brain and spinal cord [2]. Once in the CNS the T cells can be reactivated by CNS antigens presented on MHC II by other APCs, primarily microglial cells [62]. Secretion of proinflammatory Th1 cytokines by the reactivated T cells can induce CNS inflammation by activating

#### **Figure 1.**

*Multiple sclerosis pathogenesis. Autoreactive T cells, macrophages and NK cells, and demyelinating antibodies, may migrate across a compromised blood brain barrier. T cells are reactivated in the central nervous system by antigen presenting cells (APC). Anti-inflammatory cytokines released by Th2 cells can stimulate B cells to differentiate into plasma cells that secrete demyelinating antibodies. Alternatively, the release of proinflammatory cytokines by Th1 cells can enhance immune response, via activation of other immune cells such as CD8 T cells and macrophages to attack the myelin sheath and oligodendrocytes causing demyelination and the development of clinical symptoms of MS (created with BioRender.com by A Willson).*

macrophages, B cells and other T cells [63]. The antibodies can also initiate a complement cascade resulting in assembly of the membrane attack complex, forming pores in the myelin membranes.
