Danger vs. self/non-self model

Ken Frauwirth BioKen frauwirt at bacillus.Berkeley.EDU
Tue Jul 1 15:42:10 EST 1997

In article <5pb4k8$ffq at panix.com>, Ian A. York <iayork at panix.com> wrote:
>In article <33B84A2A.5CC8 at ntu.ac.uk>,  <fd601220 at ntu.ac.uk> wrote:
>My strongest feeling is that no model of the immune system is correct,
>nor can it possibly be correct.  The immune system is a thing unto
>itself, which happened rather than being created; as such it's a mishmash
>of things that work.  It is not a tidy toy railroad that can be easily
>reduced to an aphorism like "danger" or "self/non-self", as if it
>depended on advertising jingles for its effectiveness.  In other words,
>the claim that *this* model is wrong therefore *that* model is right is
>rather a silly one.
>That being said, it seems to me that the "danger" model makes more
>incorrect predictions than does the "self/non-self" model.  It's trivial
>to make immune responses to innocuous antigens--ovalbumin, KLH.  It may be
>said that the mode of administration (injection, for example) leads to
>some trauma that triggers the immune response.  Problem is, the degree of
>trauma associated with this is on the same order of magnitude as ongoing,
>perpetual trauma due to, oh, bumping into walls, spilling hot coffee on
>your hand, or getting bitten by a flea (if you're a mouse, that is; I mean
>no criticism of your persoanl hygiene). If this degree of trauma is all
>that's necessary for the "danger" signal, then there's always a danger
>signal, and so the model predicts a perpetually "on" system.  If so, the
>model is useless, because you still need other explanations for immune

I completely agree with you as far as neither model being a complete
description of the way the immune system functions.  Further, there is
room for significant overlap between them - they need not be mutually 
exclusive.  Central tolerance seems to work on a self/non-self basis, while 
peripheral tolerance may rely more on the presence or absence of danger
signals.  However, I think you are dismissing the "danger" model too 
quickly, perhaps because you have not read Matzinger's and Fuch's presentation
of it.  The basis is that one can *not* easily generate an antibody or T cell
response by simply injecting soluble antigen; in fact, such an immunization 
is likely to result in tolerance to that antigen.  Instead, coinjection of an 
adjuvant is necessary, and that adjuvant serves as the "danger" signal and 
induces an inflammatory response.  My main problem with Matzinger's "danger"
model is her insistence that it is incompatible with the self/non-self model.
While a danger signal may be needed to initiate a response, it still only
works for an antigen that has not already been determined to be "self" 
during T cell development.

Ken Frauwirth

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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