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Why do relapses go?

Posted: Tue Mar 13, 2007 11:38 am
by Frank
Hi,

I recently wondered how it could be possible, following the traditional autoimmune theory, that the immune system comes to the point where it attacks the mylin sheath and after some time/event it calms down and stays quiet until the next relapse.

As far as I know, if the immunesystem comes across an "enemy" structure the immune-cascade is going on as strong as necessary, until the enemy structure is completly removed (or at least no longer detctable to the immune system - like a latent virus).
Off course the immune-system does have are anti-inflamatory mechanisms, but these should not halt the attack until the job is done.

So in MS, when it attacks the mylin I would expect a heavey reaction that leads to the "complete" eradication of mylin at a single blow.

Does anyone of you have a conclusive idea how it comes that relapses pass off?


Thanks

--Frank

Re: Why do relapses go?

Posted: Tue Mar 13, 2007 12:48 pm
by NHE
Hi Frank,
That's a good question. I hope that this reply helps to answer it. From MRI studies, it has been shown that not all lesion activity produces clinical symptoms. For a graph depicting this process, please see page 6 of this document.
http://www.msu.edu/~lyonro/Opexa06.pdf

NHE

Posted: Tue Mar 13, 2007 2:01 pm
by Frank
NHE, thanks for answering.
I took a look at the presentation from your link and I do understand the content of the mentioned graph.

But my point is that there is a break of the immune-systems attack, isnt it?
If that would not be case, then inflamation markers in blood like CRP or T-Cell count etc. must be elevated all the time, which does not happen to be, does it?

And in case of a continuous inflamation I would MS expect to worsen much more dramatic, not some accumulated disability over years.
For example I would compare tissue rejections after organ transplantation which are indeed rapid.

So how could a break make sense, regarding, that the targeted antigen (myelin) is still present?


--Frank

Posted: Wed Mar 14, 2007 12:33 am
by CureOrBust
Lets not forget there is a another step in the MS disease process. The errant immune system has to be let into the CNS, through a BBB. Steroids are normally used to stop attacks in their tracks, and one of their modes of actions has been found to be in closing the BBB.

If we assume the immune system continues to be myelin reactive, the BBB may somehow change to stop letting it in. Then the question becomes what triggers this change.

Posted: Wed Mar 14, 2007 2:40 am
by Frank
I quote a discussion between Chris and Lyon on that subject:
Chris55 wrote:
A "P.S." here....first, one of the mysteries about MS is the T cell's ability to cross the BBB because NOTHING is supposed to be able to get through.

Lyon wrote:
Sadly Chris, although I thought the same in the beginning, things aren't quite that simple.
With further research I found that there are certain things under a certain size which can go in through even a healthy bbb and when there is problem the immune system is allowed to go in after them.
Currenty I dont have a scientific reference at hand, but I know that there was a study concerning PML in TYSABRI. Where it was found that the immune cells level in the CSF of TYSABRI patients is LOW compared to a much bigger presence in healthy controls.

So it seems common for immune cells to cross the BBB.

In relapses, even if steroids are not used (to shut down inflamation), the relapses pass off naturally after some time...
Is it the case that the inflamation needs replenishments through the BBB, because the immune-cells in the CNS would decay after some time and can not reproduce themself within the CNS?

--Frank

Posted: Wed Mar 14, 2007 2:59 am
by Frank
I just wanted to add this link to the discussion. It is mostly about how B-Cells mediate through BBB:

Determinants of Human B Cell Migration Across Brain Endothelial Cells
The Journal of Immunology, 2003, 170: 4497-4505.

--Frank