Self defined from within or from without (was the immune system is dead ! Long life ...)

Pierre sonigo at cochin.inserm.fr
Fri Feb 11 06:14:36 EST 2000


"Jamie Cunliffe" <cunlij at my-deja.com> a écrit dans le message news:
880n7h$u33$1 at nnrp1.deja.com...
> In article <87v7sa$6bf at bisance.citi2.fr>,
>   "Pierre" <sonigo at cochin.inserm.fr> wrote:
>
> > Revised hypothesis 3 (Cunliffe) : the immune system attacks the enemy
> > because it is messy.
>
> Pierre,
>
> Sorry! You are still bogged down in the conventional perspective. APCs
> simply find either a tidy set of cells that are not under stress, not
> spilt and an ECM free of the tell tale signature of spilt cells OR,
> they see the opposite. On seeing the opposite they ingest and present
> all the garbage that they tidy up for presentation to precursor T-cells
> so that it can invoke an aggressive response. Both antigens typical of
> healthy self and foreign peptides will be presented. It is only the
> fact that most precursor T-cells responding to peptides typical of
> healthy self have been mopped up into suppression (by the previous
> widespread constant apoptosis that goes on in large volume throughout
> the body) that focuses attention dominantly on what we are happy to
> call "non-self" antigens.
>
> > Evolutionary corolary : the origin of the immune system is the
> primitive
> > immune system. The function of the primitive immune system was to
> fight
> > primitive enemies. It was strongly selected because if we are killed
> by
> > enemies, we are dead.
>
> Again, convention-think has got the upper hand. I believe that I have
> shown you that you can mount a system that doesn't even look for
> enemies. It looks for cells and their debris that got uncontrollably
> sick in the past and ushers them into extinction as soon as possible on
> the next encounter.  Although this ends up as an APPARENT attack on
> foreign antigens this is the simple consequence of the fact that T-
> cells specific for these epitopes have NOT previously been mopped up
> into tolerance through widespread, physiological apoptosis.
>
> Jamie

Hi Jamie !
If you prefer :
Revised hypothesis 3 (Cunliffe) : the immune system recognizes what it has
to attack because it is in a mess, and the cells consider that everything in
a mess is an enemy.

That's a funny debate because I think *you* are glued in the conventional
thinking without even realizing it.
You propose that the immune system does not recognize the caracteristics of
the antigen but responds to something it recognizes in the environment. This
appeared as a good idea at first. However, after more thinking, many people
realized it just replaced the previous classification/recognition of the
antigen (self/non self) by a classification/recognition of the environment
(danger/non danger or mess/non mess). This is what D. Forsdyke was
explaining in his replies. More precisely, you replace a classification of
epitopes (self/non self) by a classification of environmental molecules
(called "signals") or their arrangement (mess/non mess). The basis for your
molecular classification is even more unknown (at present) than with self
non self epitopes. Like with Ptolemy epicycles, you will always need another
unknown molecule or complex combination of them to fully explain our
observations. On the epistemological point of view, you propose a new
hypothesis with more UNKNOWN factors in it, whereas an improved hypothesis
has to use LESS unknown factors. You were probably inspired by biology being
a real epistemological "mess".
To summarize : present environmental views of the immune response are a NON
progress because they rely on molecular  classifications which are are
impossible, like any classifications in biology.

I enjoy the debate ;)
Yours
Pierre








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