ImmunologyTier 2Medical Sciences concept

Multiple sclerosis pathogenesis (T cells, B cells, cytokines)

Core concept

T cell-mediated autoimmune demyelination of CNS white matter, with increasingly recognised B cell and cytokine contribution
Autoreactive CD4+ Th1/Th17 cells cross a disrupted blood-brain barrier, activate microglia/macrophages -> attack myelin (oligodendrocyte-derived)
B cells present antigen, produce oligoclonal IgG bands (CSF), and are the direct target of the most effective disease-modifying therapies (anti-CD20)

Molecular mimicry hypothesis - viral antigens resembling myelin antigens trigger cross-reactive autoimmunity; EBV now has strong epidemiological evidence of a near-necessary causal role
Key cytokines: IL-17, IFN-gamma, TNF-alpha drive relapsing-remitting (inflammatory-predominant) disease; the progressive phase is neurodegeneration-predominant and less responsive to immunomodulation
Oligoclonal bands in CSF but not serum = intrathecal antibody synthesis - supports diagnosis but is not specific

EBV as a near-universal antecedent has reframed MS pathogenesis and drug development (anti-EBV strategies in trials)
Explains why B cell-depleting therapy (ocrelizumab, rituximab) works despite MS being framed as a "T cell disease" - B cells are pathogenically central
Progressive MS responds poorly to anti-inflammatory DMTs, reflecting neurodegenerative rather than inflammatory pathogenesis at that stage

3 more sections, plus exam facts

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