FIGURE 1 | The inflammatory phase of multiple sclerosis.

From the following article:

Transcriptional analysis of targets in multiple sclerosis

Lawrence Steinman & Scott Zamvil

Nature Reviews Immunology 3, 483-492 (June 2003)


Transcriptional analysis of targets in multiple sclerosis

T cells, B cells and antigen-presenting cells (APCs), including macrophages, enter the central nervous system (CNS), where they secrete certain chemicals known as cytokines that damage the oligodendroglial cells. These cells manufacture the myelin that insulates the neuronal axon. The injured myelin cannot conduct electrical impulses normally, just as a tear in the insulation of a wire leads to a short circuit. Lymphocytes diapedese into the CNS through use of a surface receptor known as alpha4-integrin. This step is impeded by antibodies specific for alpha4-integrin or by interferon-beta (IFN-beta). Once the blood–brain barrier is breached, other inflammatory cells accumulate in the white matter. Inside the brain, T cells and accompanying macrophages and microglial cells release osteopontin (OPN), interleukin-23 (IL-23), IFN-gamma and tumour-necrosis factor (TNF), all of which damage the myelin sheath. Also, the presence of OPN might lead to the attraction of T helper 1 (TH1) cells. T-cell activation can be blocked by altered peptide ligands (APLs), such as copaxone, or by statins. Concomitantly, B cells (plasma cells) produce myelin-specific antibodies, which interact with the terminal complex in the complement cascade to produce membrane-attack complexes that further damage oligodendroglial cells. DNA vaccination can be used to tolerize T- and B-cell responses to myelin.

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