The immune system is dead! Long live the immune system!

Pierre sonigo at cochin.inserm.fr
Thu Feb 10 15:48:04 EST 2000


"D Forsdyke" <forsdyke1 at home.com> wrote: 38A20F8F.1837C940 at home.com...
> Hello,
>         BEFORE we all go rushing to the literature, why not do
> a bit of thinking? What is "danger"? It is a word applied when
> one has a certain sort of information about something. For example,
> as you approach a sunny beach you might be confronted with a sign
> saying "DANGER. LAND-MINES". In order to write that sign, someone
> had to discern that among the objects on the beach there were some
> compatible with humans (sand, pebbles, weed), and some incompatible
> ("land-mines").
>
>     Thus, first there was a binary discrimination event. The
> decision to use the "D-word" either followed or did not follow
> this event. In biological systems, a convenient nomenclature
> for this binary decision-making process is that it involves
> discrimination between "self" and "not-self".
>
>      The ability to carry out this discrimination is SO important
> that it is likely to have arisen among the very first living forms
> (unicellular). The mechanisms which evolved there may then have been
> modified and adapted when multicellular organisms arose.

<snip>
Good point. Immunology is born during a war, and is still inspired by
military conceptions. Let's summarize :
Initial hypothesis : the immune system attacks the enemy because it has a
different uniform (structure).
Revised hypothesis 1 (Matzinger) : the immune system attacks the enemy
because it is dangerous.
Revised hypothesis 2 (Zinkernagel) : the immune system attacks the ennemy
because it does not respect the frontiers.
Revised hypothesis 3 (Cunliffe) : the immune system attacks the enemy
because it is messy.
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.

Static/binary/qualitative classifications such as self/nonself
danger/nondanger mess/nonmess are -whatever the semantics- formal equivalent
of good/bad and are difficult to accept in a modern scientific elaboration.
Modern immunology is a bunch of old ideas hidden in a pseudo-technical soup.
I worked for years on AIDS vaccines and I sadly realize that we lack true
concepts to build our vaccination protocols and still do not understand how
Jenner eradicated smallpox.

Sorry to be a little provocative. Do not take it too seriously. I just wish
to stimulate discussions in the NG. I suggest, before reading recent papers
to enjoy the wonderful historical papers placed online by Dr Forsdyke
(thanks !)
http://post.queensu.ca/~forsdyke/theorimm.htm
I will indicate my prefered second step later ;)
Regards
Pierre









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