Tolerance


Mon Jul 12 12:29:50 EST 1993


In article <CA26DH.6Fy at ms.uky.edu>, woodward at seqanal.mi.uky.edu (Jerry
Woodward) wrote:
> 
> I'm new to the bionet.immunology scene.  Since there was nothing to read, 
> I decided to post a message and to see if there is anyone out there interested.
> Perhaps we need an alternative way of thinking about the immune response.
> We normally think of a response as an activation event to a foreign antigen. 
> Perhaps it is better to see it as an absence of a toleragenic signal.  In 
> other words, tolerance is the default pathway.  There is no such thing as a 
> "self" or a "non self" antigen.  It is simply the manner in which it is 
> presented to the immune system.  This is probably controled to a large degree
> by a complex interaction of cytokines.  
> 	The TGFbeta knockout mouse is a case in point.  If T cell receptor 
> repertoire is so important, why did this mouse come down with massive,
> multifocal autoimmunity?  This suggests that we all have a very great number
> of self reactive clones, but that self tolerance is maintained by cytokines
> such as TGFbeta.  
> 	I could go on for a while-- Is there any discussion?

The concept of lack of tolerance is well established in the immunology
world.
Self and non-self are human concepts, but there it is useful since it
is relevant in thinking about the role of the thymus.  Supressor cells
had gotten to be a dirty name, but the response of a supressor is to 
down modulate an immune response.  So there are positive responses that
are both activating and deactivating in nature.  

By the way, there was a short review in Immunology today a while ago 
that modelled the immune response.  It used a cute system of a limited
immune system with 256 antigens (taking advantage of 8 bit computer 
systems) and produced kinetics similar to a natural immune response.
I look forward when we know enough about cytokines to make a computer
model which will incorporate soluble factors.

Steve Holland 



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