From the Wash Post

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From the Wash Post

Postby dylan48 » Thu Feb 08, 2007 4:06 pm

I like this its understandable

Because parasites often cause long-lasting infections, the researchers hypothesized that such infections could make persistent demands on the body and thereby reduce the likelihood that the immune system will attack healthy tissue.
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Postby Lyon » Thu Feb 08, 2007 4:29 pm

Hi Dylan,
I've seen researchers put it that way so people can grasp it. At some level that does explain the situation, but there is more to it than that.

I mentioned William Harnett of the University of Strathclyde in an earlier response....as it happened, I was reading Dr Harnett's editorial in the October 2005 issue of Parasite Immunology when I noticed your post and this paragraph coincidentally addresses the situation pretty well
The concept that parasites modulate the immune system ensures that there is great interest in establishing the nature of the parasite molecules involved. Such interest indeed predates the awareness of parasites polarizing rather than suppressing the immune system, but although some 'immunosuppressive substances' were identified in earlier years [e.g. (6)], in general characterization was poor at the molecular level. Boosted by the recent advances in protein purification, molecular cloning and genome sequencing, the situation is now very different. Thus, the identities of literally scores of parasite molecules that have either been shown to, or are likely to, play a role in modulation of the immune response are now known [e.g. (7)]. Furthermore, whereas in the past the activity of parasite products was assessed only by their effect on immune responses measurable at that time, such as lymphocyte proliferation or antibody production, it is now possible to investigate immunomodulation with respect to the disciplines of biochemistry and molecular biology. Hence, for example, we can define the receptor that parasite products interact with, the signal transduction pathways that are then activated, and the effects on gene transcription that then ensue. Put together, in simple terms it is now possible to establish what molecules a parasite employs to modulate the immune response, how they work and what the consequences are.

Bob

Later edit. Regarding the statement in the article you included...I've heard that factor described as "persistance" and it's with the idea that originally the body notices and labels antigens on the parasite for destruction but before the immune system can destroy the parasite it changes it's external glycoproteins. This again requires the immune system to identify and label it for destruction. The idea is that the worm is constantly one step ahead of the immune system by changing its external glycoproteins (variant surface glycoprotein or "VSG") which, as the article hinted, keeps the immune system occupied and possibly teaches the immune system "tolerance" to some degree
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Postby CureOrBust » Fri Feb 09, 2007 1:27 am

This "VSG" causing "tolerance" within our immune system is a new concept for me, and interesting at that. Does anyone know of any studies using a drug/chemical which works using the same modality? If not, I think its a line worth some reasercher following. hello? are any reading?
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Postby Lyon » Fri Feb 09, 2007 6:35 am

Hi Cure,
I've been wondering recently what is taking the researchers so long to isolate and replicate whatever it is that the worms do. What could be so complicated?

Although there's a lot more to the effect the worms have on the immune system than just this VSG, the very nature of VSG alone would be nearly impossible or impossible to ever replicate in pill form. Not that the worms are rocket scientists but they have an array of over 1,000 glycoproteins which they are at least smart enough to change one step ahead of the immune system. I thought it was interesting that if there are 500 parasites in the body....all the parasites present the same glycoprotein the same time so that the immune only gets to experience one at a time, which means that their array of variables could keep the immune system occupied for a very long time.

I read one paper last night in which the researcher said that longevity is a clear sign of success and that some human parasites live for decades despite the best efforts of our immune system. That really is mastery of our immune system.

As usual I've gone off on a tangent. Nope, I don't know of any drug or chemical and to be honest I can't imagine how you would/could replicate variability in pill form.

Bob




CureOrBust wrote:This "VSG" causing "tolerance" within our immune system is a new concept for me, and interesting at that. Does anyone know of any studies using a drug/chemical which works using the same modality? If not, I think its a line worth some reasercher following. hello? are any reading?
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Postby TwistedHelix » Fri Feb 09, 2007 10:53 am

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/G/Games.html


This link will take you to a page which discusses some of the tricks that many parasites play on our immune system. It seems that VSG is not only used by worms but other invading organisms as well -- I was particularly interested to read that infection by Trypanosomes can cause a relapsing-remitting form of illness. At a guess I imagine the process goes something like this:

The body recognises an enemy epitope, (the pieces of protein which enable the body to recognise foreign tissue), and begins the process of building antibodies against it.

Once the numbers are sufficient, the invader presenting that epitope is attacked and destroyed.

However, by this time, using VSG some of the invading organisms have hidden themselves from the immune system by covering themselves with new glycoproteins. It takes some time to mount a defence against this "new" invader, during which both the antigen and antibody numbers rise, and the cycle begins again. Therefore there is a roller-coaster of fluctuating attack and defence, as numbers rise and fall, which results in the relapse and remission characteristic of some illnesses. That's my interpretation, anyway.

I was also interested to see that worms use the same technique not only to avoid an immune response, but to stop further infestation from competing worms... I'm not sure I understand how this works, but it would be a mechanism to avoid over- infestation.

Dom.
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Postby Lyon » Fri Feb 09, 2007 11:13 am

http://www.ovamed.de/english/casereport ... report.php
Interesting parasite links. Some specific to MS, some specific to EAE and others mentioning MS but are about IBD.
Bob
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