Figure 5.

Two opposing paradigms explaining the cause of autoimmunity in MS. The prevailing concept is the outside-in paradigm, namely that infection of individuals who are genetically predisposed to MS with an as yet unidentified microorganism activates autoreactive T and B cells present in the normal immune repertoire. The autoimmune attack on the CNS induces cytodegeneration. Less commonly accepted is the inside-out paradigm, which states that a pathogenic event inside the CNS elicits the release of myelin antigens that activate autoreactive T and B cells present in the normal immune repertoire. The principle difference between both paradigms is that in the outside-in paradigm infection is the direct trigger of autoimmunity, whereas in the inside-out paradigm infections create a higher responsive state of the immune system.