Figure 2: Multiple sclerosis pathophysiology. Contact in early childhood with a pathogen plus other susceptibility factors as racial and demographic background can elicit their reactivation, triggering innate mechanism of defense as toll-like receptors (TLRs), that signalizes downstream through MyD88 (myeloid differentiation primary response 88), and phosphorylated IκB which permits translocation of NF-κB and the transcription of IL-6, TNF, IL-1, IL-12, E-selectin, MCP-1, and IL-8. TLR through IRF7 (Interferon regulatory factor 7) gives the signal to the transcription of IFN α/β. Another important signal is given by NOD receptors (nucleotide-binding oligomerization domain) activated also by potassium efflux-inducing agents such as ATP and TLR stimulation; PAMS, toxins, danger or stress triggers induce the inflammasome via NLRP that form a complex with ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1, activating IL-1B, a major factor inducing inflammation, autophagy and cell death, particularly necrosis. All these proinflammatory soluble factors activate microglia and endothelial cells, upregulating expression of adhesion molecules as E-selectin, facilitating the migration of T cells into the SNC. Matrix metalloproteinases (MMP) degrades BBB (blood brain barrier) enhancing further migration of autoreactive T cells and macrophages via chemokines (CX3CL-1). The Th1 response evocated via IL-12 and IFN-γ further activates macrophages that in turn do so to T cells CD8+. Th2 response via IL-6 mainly stimulates maturation of B cells and production of autoantibodies. Cytotoxic damage to the oligodendrocyte mediated myelin loss and exposure of the axon to reactive oxygen species, slowing or blocking action potentials and the production of neurological spectrum. There are intents to remyelinate these lesions via OPCs (oligodendrocyte precursor cells), but neuronal factors such as LINGO-1 or TLR2 inhibit their migration.