Table 1.

Summary of the present information about MS

Feature	Mechanism of Disease	Ref
Therapy	MS has a heterogeneous nature. Each effective treatment has responders and non-responders. If the treatment is initiated sooner in the course of the disease, the probability of the therapy's efficacy increases. Effective therapy requires pulse or constant treatment and, eventually, combined treatment. The keystone of MS immunotherapy is identifying MRI and immune biomarkers; thus, no evidence of disease activity (NEDA) would be achieved.
Autoimmunity	MS is a cell-mediated autoimmune disease directed against CNS myelin antigens involving CD8+ and CD4+ cells. There is an enhancing or secondary role for Autoantibodies. The body of normal individuals possesses Autoreactive T cells against myelin elements, and it does not develop the disease in these individuals. It even could provide protective properties for the brain. With the induction of pathogenic Th17- and Th1-type and CD8 myelin autoreactive T cells, MS is developed.
Infection	Myelin-reactive pathogenic T cells could be induced by Infectious agents. The related possible mechanisms are cross-reaction with the central nervous system's myelin antigens, activating an extended autoreactive immune repertoire, or a self-limited infection of the brain releasing myelin antigens. A lasting brain viral infection or transmissible agent is not the cause of MS.
Genetics	The risk factors of MS development include MHC and non-MHC genes. Immune repertoire is determined by MHC genes, while tolerance and regulatory mechanisms in MS are determined by non-MHC genes that both of them are defective.
Environment	The risk of MS development and its course would be increased by Environmental factors, including low UV radiation exposure, low vitamin D, cigarette smoking, EBV exposure, and obesity.
B cells	B cells centrally play a role in MS. Similar to T cells, anti- and pro-inflammatory B cell subgroups are available. These cells work as the main antigen-presenting cells in relapsing MS, driving pathogenic T cells. B cells in progressive MS are an enhancer of the compartmentalized central nervous system responses achieved via secreted factors and lymphoid follicles.
Microbiome	The function of T cell is regulated by the microbiome in the body, which is composed of pathogenic microbial and protective components that have a crucial role in MS since they establish immune set points and secrete metabolites.
Relapsing MS	Immune cells migrating into the CNS drive Relapsing MS. It has been shown that there are some effective therapies for treating relapsing MS (reducing relapses and new MRI lesions). These treatments work on these pathways: reducing function and/or the number of effector cells, increasing function and/or the number of regulatory cells, and preventing cell traffic to the CNS.
Progressive MS	Mechanisms of Progressive MS are of immune-dependent and immune-independent types. The brain establishes an innate immune response in mechanisms dependent on the immune system. Such response includes macrophages, lymphoid follicles, microglia, and B cells. Also, chronic activation of innate cells and peripheral T cells could be involved. In immune-independent mechanisms, we observe oxidative stress, ion imbalance, and mitochondrial injury. The available treatment does not effectively target these processes.
Autoantigen	The provoking autoantigen in MS is not known. Nevertheless, with the diagnosis of MS, there is not any singly single autoantigen for targeting since reactivity is spread to other organ-specific antigens, similar to what happens in type 1 diabetes. Therefore, in antigen-specific treatment, bystander suppression should be employed or presented as a preventative strategy for vulnerable individuals.