Danger vs. self/non-self model

Mike Clark mrc7 at cam.ac.uk
Wed Jul 2 14:07:19 EST 1997

In article <5pb4k8$ffq at panix.com>, Ian A. York
<URL:mailto:iayork at panix.com> wrote:
> In article <33B84A2A.5CC8 at ntu.ac.uk>,  <fd601220 at ntu.ac.uk> wrote:
> >RecentHorizon tv prog convinces me that the self/non-self model is
> >wrong;
> >how will the fact that the 'danger' model isv.prob. the case change
> >immunological treatments + reserch.How duz the danger model explain
> >food allergies+  rejection of foreign grafts?
> I'm half with you.  The "self/non-self" model isn't entirely correct.  On
> the other hand, the "danger" model is also not entirely correct, and in
> my opinion it is less correct than the self/non-self.
> 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
> regulation. 

I have to disagree with you on the statement that it is "trivial" to make
immune responses to "innocuous antigens". On the contrary immunologists
either tend to work with selected antigens which are strong immunogens or
they have to resort to combining them with adjuvants etc. It seems to me
that evolution has endowed the innate immune system, macrophages,
neutrophils, eosinophils, complement etc, (and you might even stretch to
including CD5 B-cells, and perhaps gamma delta T-cells in this catogary),
with an ability to recognise some common signals associated with infection.
The innate immune system then kick starts the adaptive response which in it's
turn leads to the production of cells and immunoglobulins which might be 
cross-reactive on new infectious agents and enhance the innate response and
hence back through the cycle.

Mike Clark,                        <URL:http://www.path.cam.ac.uk/~mrc7/>
 o/ \\    //            ||  ,_ o   M.R. Clark, PhD. Division of Immunology
<\__,\\  //   __o       || /  /\,  Cambridge University, Dept. Pathology
 ">    ||   _`\<,_    //  \\ \> |  Tennis Court Rd., Cambridge CB2 1QP
  `    ||  (_)/ (_)  //    \\ \_   Tel.+44 1223 333705  Fax.+44 1223 333875

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