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