Re: OT: Senile, drunken hymenoptera


Jeff Lanam wrote:
On 12 Sep 2006 09:07:31 -0700, "Noone Inparticular"
<unreve89@xxxxxxxxxxx> wrote:


Robert Grumbine wrote:

What's so intelligent about a defense system which is liable to kill you
itself? (n.b. recent _Discover_ magazine has an article about our T cells
not having 'brakes' which the other primates do have, and linking that to
our horde of auto-immune response illneseses.)

What?!? They most certainly do. Discover magazine is an unreliable
source. Or maybe you're misremembering?


I read the article, too. It said we don't have "as many of those
brakes."
http://www.discover.com/issues/sep-06/rd/uniquediseases/

Last March the German biotech company TeGenero began testing the drug
TGN1412 on human volunteers. The result was one of the most disastrous
clinical trials in history. Although TGN1412 is harmless to other
primates at high doses, it sent the immune systems of six people into
near-deadly overdrive, causing widespread inflammation and
multiple-organ failure.

Two months later hematologist Ajit Varki of the University of
California at San Diego published a paper offering a plausible
explanation for why things went so wrong. The drug hit humans so much
harder, he says, because of a difference in the surface molecules of
our white blood cells. Varki studies siglecs, small groups of
receptors that thickly stud the immune T cells of monkeys and apes but
are few and far between in humans. Siglecs act as brakes, stopping the
immune system from overreacting. Because human T cells don't have as
many of these brakes, our cells are a hundred times more aggressive
than those of chimps when faced with drugs like TGN1412, which work by
triggering the immune system.

OK, here's the problem with this kind of thinking; we are not in the
business of looking for therapies for non-human primates. Why is this
significant? Because if we were we would undoubtably find all sorts of
drugs that have the effect of things like TGN1412 on non-human primates
but not on us.

There undoubtably is a reason why humans respond the way that they do
to TGN1412 and certain sialic acid binding proteins (which are what
siglecs are) may in fact be that reason. But that in no way implies
that humans are not capable of attenuating immune responses. As a
matter of fact, a good deal is known about how immune responses are
attenuated in humans. We also know a good deal about autoimmunity, only
a fraction of which are T cell mediated. We may have different
mechanisms for immune attenuation than non-human primates, but we do
have them. Furthermore, non-human primates do suffer from autoimmunity
but because they are not (a) human and (b) do not have a large public
research granting agency on their behalf, we are not so interested in
ferreting out the sorts of diseases they suffer. That is to say that
whether or not siglecs are actually important mediators of human
immunity does not imply a qualitative difference with non-human primate
immunity.

This article is an example of sloppy science journalism.

.

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