complement/transplantation question

Mike Clark mrc7 at cam.ac.uk
Fri Jun 5 04:27:25 EST 1998


In article <Pine.GSO.3.96.980604174405.28467A-100000 at dilbert.ucdavis.edu>,
L.A. Pike-Nobile <URL:mailto:ez063669 at mailbox.ucdavis.edu> wrote:
> 
> The valves used in valve replacement are fixed (in gluteraldehyde, I
> think). Presumably this process destroys all the surface MHC, avoiding an
> immediate anti-xeno response.Maybe no further response is developed
> because there is no shedding of antigens and valves aren't dangerous...
> 
> -L
> 
> Of course that doesn't explain lack of NK attack.
> 

As the question below states one of the  aims behind the transgenic pigs is
to avoid the hyperacute rejection (which for xenografts happens in minutes)
mediated by complement activation. The pigs are made transgenic for
molecules such as human CD59 and DAF which serve to regulate the activation
of human complement. Where I think the questioner is wrong is in thinking
that only alternative pathway activation is important. My understanding is
that xenografts from pigs exhibit antigens, many of them glycoproteins and
glycolipds, which not only activate the alternative pathway but which also
react with anti-carbohydrate antibodies (eg blood group antibodies) which
then activate the classical pathway.

Pigs transgenic for human MHC is a second strategy to try and avoid
rejection by cell mediated immunity which usually takes much longer, days
to weeks, to happen.

As to the original question I don't know enough about which antigens might
be expressed by pig heart valves to know why hyperacute rejection is not
seen.  

> 
> On Thu, 4 Jun 1998, Bob Scibienski wrote:
> 
> > 	 A while back when teaching my immunology class about
> > transplantation I told the students about the attempts to produce human
> > complement regulator transgenic pigs to avoid alternate pathway
> > mediated hyperacute rejection of their organs by human recipients.  A
> > very astute student asked why the pig valves which are routinely used
> > for valve replacement operations are not rejected by this mechanism. 
> > Anybody out there got any explanations?
> > 
> > Bob Scibienski
> > UC Davis
> > 
> > 
> > 
> 
> 

Mike Clark,

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