Polly Matzinger's theory

Ken Frauwirth BioKen frauwirt at bacillus.Berkeley.EDU
Fri Jun 7 18:41:58 EST 1996

In article <9605078341.AA834192737 at WRSMTP-CCMAIL.ARMY.MIL>,
 <dr._jack_komisar at WRSMTP-CCMAIL.ARMY.MIL> wrote:
>          I heard the talk that Polly Matzinger gave at the AAI
>          convention in New Orleans, saying that the role of the
>          immune system is to discriminate danger from
>          non-dangerous substances, rather to discriminate
>          self from nonself.  The theory seems reasonable to me, but I
>          don't see how it can accomodate positive selection of
>          thymocytes (e.g., Sha et al., Nature 336:73 1988 and Mike
>          Bevan's talk at the meeting).  Does anyone have any thoughts
>          on this?
>                                               Jack Komisar

It seems to me (and this came up when Polly posted her ideas here about a 
year ago) that there is no mutual exclusion between this theory and the
classical "self/non-self" ideas.  It is unfortunate that Polly promotes her
idea as opposed to self/non-self, since it really isn't.  Self/non-self
selection in the thymus (and bone marrow for B cells) reduces the number of 
autoreactive lymphocytes to a point where they can be handled by peripheral
tolerance mechanisms, which use "danger" signals as their cues.  The two
systems may have evolved quasi-independently, since evolution isn't directed,
and both were retained because neither alone is as good as both together.
We know that peripheral tolerance *can* be broken, so it is better that there
aren't too many autoreactive cells around.  But it is also likely that some
(or many) self-antigens are not presented in the thymus, so better to have
a back-up system, which can also reduce reaction to innocuous environmental
antigens (food is chock-full of foreign antigens).  Just ask anyone with

The real problem is the unnecessary assumption that there is only one 
underlying criterion for inducing tolerance.

Ken Frauwirth (MiSTie #33025)                         _           _
frauwirt at mendel.berkeley.edu                         |_) *    |/ (_ |\ |
http://www.ocf.berkeley.edu/~frauwirt/               |_) | () |\ (_ | \|  
DNRC Title: Chairman of Joint Commission on In-duh-vidual Affairs

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