Figure 1.

(A) Acute MS exacerbation: 1) Complement factors leak through a compromised BBB. T and B cells infiltrate the parenchyma and are activated by myeloid APCs. 2) Activated C3b and C3d deposit on myelin promoting its opsonization. C1q binds resting microglia and modulates its phenotype switch to disease-associated microglia (DAM). 3) Downstream activation of complement leads to MAC formation and damage to the myelin membrane. (B) Progressive MS: 1) Complement and other factors are secreted by DAM and by the tertiary lymphoid tissue (TLT) and diffuse into the brain parenchyma. 2) C3-bound myelin products are opsonized by myeloid cells and activated microglia. 3) In this stage, MAC formation exerts protective effects through the apoptosis of inflammatory cells and prevention of OLG apoptosis (Created with BioRender.com).