Ana sayfa | MS’in Derinliği  | MS Slide Resource

Having discussed the potential roles that the many immune system components may play in MS pathogenesis, it is possible to put all the components together into a coherent model. This model is unlikely to be the complete story, but is the most likely sequence of events given the present evidence. It allows a confusing subject to be understood, by giving a conceptual framework on which to hang the facts.

The model

Some individuals are rendered susceptible to MS by their genetic constitution. It may be that they have a particular set of self-recognition genes in the MHC Class II area of their genome (the area that codes for antigen presentation functions). When such individuals encounter a specific, unknown, environmental trigger, a dormant pool of autoreactive T-lymphocytes becomes activated.

These activated T-lymphocytes cross the blood-brain barrier and survey the CNS for their target auto-antigen. The elements necessary to initiate inflammation are an antigen, an antigen presenting cell and a sufficient concentration of T-lymphocytes specific for that antigen. Once this threshold is reached, inflammation can begin.

Activated T-lymphocytes release interferon gamma. This attracts further T-lymphocytes and activates macrophages. The macrophages phagocytose myelin, release toxic cytokines (TNF) and present more antigen to T-lymphocytes. Consequently, activation and recruitment of additional different T-lymphocyte clones occurs. T-lymphocytes also produce toxic cytokines of their own (TNFß).

This inflammatory reaction directly damages myelin and oligodendrocytes, but also causes bystander damage to the blood-brain barrier, allowing leakage of more immune cells and molecules into the brain. As a result, B-lymphocytes, antibody and complement join the attack.

T-lymphocytes enhance B-lymphocyte expansion, which in turn may produce autoantibodies. The autoantibodies can act synergistically with T-lymphocytes to cause further myelin and oligodendrocyte damage. Also, autoantibody and complement act as opsonins to encourage macrophage attack. In addition, complement forms membrane attack complexes which destroy oligodendrocytes by causing a massive influx of calcium ions into the cells.

So, typically, an area of MS inflammation surrounds a central vein that has a damaged and leaky blood-brain barrier. In this area of inflammation, T-lymphocytes and macrophages predominate. Antibodies, complement and cytokines aid the attack.

Ultimately, myelin debris is phagocytosed by macrophages and the nerve axons left naked. The naked axons cannot conduct electrical impulses efficiently and so the typical symptoms and signs of MS result.

For an unknown reason remission can occur. The inflammation subsides, the blood-brain barrier is restored and the nerve fibres often remyelinate. However, repeated healing and reappearance of a lesion on the same site eventually leads to the formation of an old, scarred, demyelinated plaque.

This model is intended to be unbiased by any research interests into one particular component of the immune system. It is a useful framework, but will undoubtedly require modification in the light of future insights into MS immunopathogenesis.

Bu sayfadaki bilginin en son güncellendiği/doğrulandığı tarih:

11/09/2001

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