How does de-myelination occur in multiple sclerosis?

Question

From what I understand, only the oligodendrocytes are affected in multiple sclerosis, and they are attacked by T cells which cross the blood-brain barrier. This leads me to two questions:1. How is the blood-brain barrier affected in MS that allows T lymphocytes to cross the barrier?2. Why do the T lymphocytes attack the oligodendroccytes? And when they do, what is the mechanism for de-myelination?Thank you in advance!

Answer 1

Autoimmune activation (autoreactive T cells and B cells recognize myelin proteins) → Enter Blood–brain barrier disruption and immune cell infiltration → Inflammatory cytokine and chemokine release (IFN-γ, TNF-α, IL-17, IL-1β, IL-6, CCL2, CXCL10) → Macrophage and microglial recruitment → Oligodendrocyte death → Demyelination → Reactive astrocyte and microglial activation (Compensation Mechanim)→ Chronic neuroinflammation and failed remyelination → Axonal degeneration and irreversible neurological disability.

Answer 2

Hi!

At present, the exact mechanisms leading to BBB breakdown in MS are incompletely understood; however, it's thought that the release of inflammatory chemokines and cytokines may contribute. Reactive astrogliosis and defects in BBB junctional proteins may also contribute.

The T-cells involved in MS pathology are auto-reactive T cells. This means they recognize and respond to not foreign antigens, but antigens on our own cells. These are often myelin proteins, such as myelin basic proteins. Although our body has many mechanisms to eliminate self-recognizing T-cells, those mechanisms are imperfect, and so the activation of these self-recognizing T cells is possible.

Because these T-cells target myelin proteins, the loss of these proteins results in destabilization of the myelin sheath, and subsequent demyelination (although the exact mechanisms of demyelination are still being investigated).