Multiple
sclerosis is a demyelinating disease of the central nervous system, which
includes the brain and the spinal cord.
In other words, it is a idiopathic auto immune disorder and it primarily affects the white matter of brain. It is one disease almost exclusively of the central nervous system.
Myelin is
the protective sheath that surrounds the axons of neurons, allowing them to
quickly send electrical impulses. This myelin is produced by oligodendrocytes,
which are a group of cells that support neurons.
In multiple
sclerosis, demyelination happens when the immune system inappropriately attacks
and destroys the myelin, which makes communication between neurons break down,
ultimately leading to all sorts of sensory, motor and cognitive problems.
Now the
brain including the neurons in the brain is protected by things in the blood by
the blood brain barrier (BBB), which only lets certain molecules and cells
through from the blood. For immune cells like T and B cells that means having
the right ligand or surface molecule to get through the blood brain barrier. Once a
T cell makes its way in it can get activated by something it encounters - in
the case of multiple sclerosis, it is activated by myelin.
Once the
T-cell gets activated, it changes the blood brain barrier cells to express more
receptors, and this allows immune cells to more easily bind and get in, multiple
sclerosis is a type IV hypersensitivity reaction, or cell-mediated
hypersensitivity. And this means that those myelin specific T-cells release
cytokines like IL-1, IL-6, TNF-alpha, and intereferon-gamma, and together
dilate the blood vessels which allow more immune cells to get in, as well as
directly cause damage to the oligodendrocytes. They cytokines also attract
B-cells and macrophages as part of the inflammatory reaction. Those B-cells
begin to make antibodies that mark the myelin sheath proteins, and then the
macrophages use those antibody markers to engulf and destroy the
oligodendrocytes. Without oligodendrocytes, there's no myelin to cover the
neurons, and this leaves behind areas of scar tissue, also called plaques or
sclera. In multiple sclerosis, these immune attacks typically happen in bouts. In
other words, an autoimmune attack on the oligodendrocytes might happen, and
then regulatory T cells will come in to inhibit or calm down the other immune
cells, leading to a reduction in the inflammation. Early on in multiple
sclerosis, the oligodendrocytes will heal and extend out new myelin to cover
the neurons, which is a process called remyelination.
Unfortunately, though, over
time as the oligodendrocytes die off the remyelination stops and the damage
becomes irreversible with the loss of axons.
