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Course: Health and medicine > Unit 8
Lesson 11: Multiple sclerosisMultiple sclerosis pathophysiology
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- Is MS specific to the CNS? Or can the auto-antibodies target myelin from Swann cells in the PNS too?(5 votes)
- Good question. MS is specific to the CNS. There is another disease process that acts similarly in the PNS called Guillain-Barre syndrome. We don't definitively know why it happens, but we speculate it's because of an autoimmune response triggered by infection or vaccination.(5 votes)
- what causes the T-cells to pass through the blood-brain barrier initially?(3 votes)
- Is there a cell signaling pathway associated with multiple sclerosis?(2 votes)
- What are the current family of disease-modifying drugs actually doing to "treat" MS? Are they helping the oligodendrocytes repair the myelin? Are they stopping the T-cells, B-cells, and macrophages (i think I've heard they're immunosuppressant)? Or are they seeking to repair the BBB?(1 vote)
- Prednisone is given to suppress the immune system. Prednisone will decrease the secretion of interleukin-2, which will cause a decrease in the proliferation and maturation of immune cells such as B plasma cells. A decrease in the proliferation of B plasma cells will cause a decrease in the release of these auto-antibodies.
Natalizumab is given to decrease the ability of these auto-antibodies in passing the blood brain barrier and reaching the myelin sheaths made up of the oligodendrocytes.(2 votes)
- What is the physiology behind the remission phases?(1 vote)
- Remyelination is the remission phase, but it's only so effective.(1 vote)
- Why does the t-cell attack the myelin and not other parts of the neuron or other cells in the brain, like glial cells?(1 vote)
- The T-Cell only attacks the myelin because, for an unknown reason, it recognizes the myelin as foreign, so it naturally wants to destroy it. This is what happens to a person with multiple sclerosis. It's not because myelin is actually bad, it's just what the T-Cell recognizes it as, which is a mistake. Hope this helped :-)(1 vote)
- How does the T-Cell get past the endothelial cells? Does it use a chemical process or something else?(1 vote)
- At6:27, it says that remyelination becomes less and less effective as time goes on. Is there a specific reason why? Do oligodendrocytes become less effective or are they just overpowered by the attacks?(1 vote)
- Yes - oligodendrocytes can only myelinate so many axons. And there are few new oligodendrocytes being produced. Also, MS attacks oligos in some cases.(1 vote)
Video transcript
- So here I have a brain slice of someone who's looking at you, and you'll notice that there's kind of this exterior portion and then there's this
interior portion as well, and I've kind of color-coded both of them. We'll be, we won't be focusing too much on this blue part right here. So this exterior part is
what we call the gray matter, and this interior part is
called the white matter. And of course in this sketch, it's not actually gray and white, but if you look at a real brain, you'll notice that the
exterior is kind of gray, and the interior is white. So what makes up the
gray and white matter, well, if you'll remember,
the brain is made up of about 86 billion neurons. Those 86 billion neurons are gonna compose the gray matter and the white matter. So let me actually draw
a neuron over here. So here, you know, we have the dendrites, here we have the cell
body, this is the axon, and this is the myelin. So you'll notice that I've kind of drawn the cell membrane in kinda the
same color as this exterior. And the reason why I do that is because the cell membrane is what's gonna give that gray matter its gray color. So the dendrites and the cell body kinda have this cell membrane, and that's really what gives
the gray matter its color. Now the axon also has some cell membrane, but the axon also has
myelin, and it's the myelin that's gonna give the
white matter its color. So the dendrites in the cell body are gonna compose the gray matter, and the myelin that's
wrapped around the axon is gonna compose the white matter. To next, let's say that this person develops multiple sclerosis,
and what we'll see are these lesions that kinda form throughout the white matter of the brain. That actually makes sense
because in multiple sclerosis, the myelin that gives the
white matter its color begins to degrade away. And the reason why it does that is because the immune
system mistakenly recognizes the myelin as foreign, and attacks it. So how does the immune system actually make its way into the brain? Well, ordinarily, the immune system travels through blood vessels, so the brain needs to
receive a lot of nourishment from these blood vessels,
and the immune system is actually going to travel
through these blood vessels. So what we're gonna do is we're actually gonna zoom in on a segment of the brain, so let's take a look at this
particular segment over here. So here we have our blood vessel. So with this blood vessel,
we're actually gonna have these cells that outline
it, called endothelial cells. These endothelial cells will be really holding on to each other
really tightly up here, like as if they're kind of holding hands really really tightly, and these points where they really hold tightly
are called tight junctions. And these endothelial
cells are kinda sitting on this foundation, right, kind of like a foundation of a house. So this red line that
I've kinda drawn here, and we call this the basement membrane. Together, these will compose what's called the blood brain barrier,
so the blood brain barrier. The blood brain barrier is
a pretty special structure because it stops a lot of
things from entering the brain, things that you really don't
want to enter the brain. So for example you know,
let's say we have a virus, and we really don't want that
virus to enter the brain, because once it does, it'll
start to do a lot of damage. So the blood brain barrier is gonna stop that from happening. It also stops your immune
system from entering the brain. So you know, maybe you have a, maybe you have like a T cell over here, which is one of your immune cells, so let's say it's a T cell. It won't really be able
to enter the brain, right, usually the immune system has some pretty limited access to it. But, in multiple sclerosis, these T cells are really able to squeeze
past the entothelial cells and break through the basement membrane. And then that way, they can actually make their way into the brain. And so now, there really have
access to a lot of the brain, and this is pretty bad, right, because this is actually
an unfamiliar environment for that T cell, because it
usually shouldn't be there. Now remember, in your brain, you have a whole bunch of neurons, right, so let me actually draw
another neuron over here. So you have the myelin
over here, and myelin has some pretty distinctive
features on it, right? So it's gonna have some proteins that may kind of be at
the surface of the myelin. The T cell may go to that protein and recognize it and say "hey, you know," "this for some reason doesn't look good." "For some reason, this looks foreign," "and I think that we
should start to attack it." And of course, it's mistaken, because, you know, it thinks that it's foreign, but in reality, it's part of the body. So once the T cell kind of recognizes that part of the myelin, it'll
start to go haywire, it'll kind of set off this alarm. So what it'll do is it's gonna release these chemicals called cytokines. And cytokines are gonna do
a lot of different things. One thing they can do is they
can promote the degradation of the blood brain barrier, so now the blood brain barrier
becomes a lot more permeable to a lot more cells, right? So now, some more T cells can come in. The cykokines can also
recruit other immune cells, so maybe we have a B cell over here, so here's a B cell, it's now able to enter the blood brain barrier, so now all of a sudden, you
have these B cells in here, and they're gonna make these
antibodies for the myelin. And once they make the
antibodies for the myelin it's gonna target that myelin
for further degradation. And then you may also even
have some macrophages. And the macrophages are really
gonna eat up that myelin and really physically degrade it. And then finally, those cytokines can actually be toxic
to the myelin as well. So the cytokines can themselves degrade all that myelin. So now what you have is just a whole bunch of degraded myelin. So now we have a whole
bunch of immune cells that are really clustered
around a part of the brain, and when this happens, we
call this neuroinflamation. So this is pretty bad, right? But, as it turns out, the
brain actually does have a way of repairing itself. So, how does it do that? Well, let's say we have
another neuron over here. So that myelin is
actually gonna be provided for the neurons by these cells over here. These cells are not neurons, in fact, they're called oligodendrocytes, and when that myelin is degraded away, this oligodendrocyte
will begin the process of remyelination. So it's gonna try to repair
all that damaged myelin. And so this is great, right, this means that the brain has a
natural healing process. And we call that remyelination. But, as time goes on, that remyelination actually becomes less and less effective. So the oligodendrocyte will really try to remyelinate the axon to
the best of its abilities, but, it'll ultimately
just become overwhelmed by the power of the immune system. And the immune system
will be really persistent, right, these T cells will
just constantly release all these cytokines, those B cells will always be around to
release those antibodies, and the macrophages will always be around to actually phagocytize
those, that myelin. So, ultimately what we have
is this remyelination process that's being overpowered
by the immune system.