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

Pierre sonigo at cochin.inserm.fr
Fri Feb 11 15:12:01 EST 2000


"Jamie Cunliffe" <cunlij at my-deja.com> a écrit dans le message news:
88139h$6bk$1 at nnrp1.deja.com...
> In article <880qur$1edi$1 at news5.isdnet.net>,
>   "Pierre" <sonigo at cochin.inserm.fr> wrote:
>
>
> > 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.
>
> Pierre,
>
> You have still included "enemies". I want to exorcise enemies.
>
> The system is basically like a phagocyte with memory. All the immune
> cell additions are simply embroidery to enhance the efficiency of its
> base phagocytic functions. Phagocytes can act at a low (quiet) level or
> a souped up "bash almost everything in sight" level. If it's in the
> second it needs to ensure that the most likely survivors of this
> battleground are healthy-self-cells. Now, it is already fairly clear
> that healthy-cells, in gap-junctional communication, are differentially
> resistant to the effects of TNF.
>
> (My) Revised hypothesis 3 (Cunliffe) : (Simply) Clears away spilt
> tissue mess and cells (particularly small) sporting membranes that do
> not have a healthy-self signature.
>
> Antigen presenting cells will try and ingest the following
>
> (1) "stuff" in the ECF that they know should not be there - especially
> anything with the signature of spilt cells
> (2) cellular material that does not carry a typical healthy-self
> signature (CAMs and complement protection ligands)
> (3) probably, small (bacteria) sized particles - possibly a remnant
> from "food recognition".
>
>
> > 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).
>
> That "something in the environment" is simply the material a phagocyte
> deems in need of ingestion. The point I made earlier is that (even if
> this is a relatively sparse arena for reductionistic dissection)
> phagocytes are doing this even in the lowliest invertebrates. The
> anamnestic immune system simply evolved to separate the phagocyte
> function of ingestion from its subsequent amplification of
> inflammation. It is not that I am going round in Ptolemeic epicycles.
> It is that you are ignoring a glaring fact that phagocytes (even in
> sponges and simple invertebrates) "know" the signature of "tissue
> mess". I've provided some suggestions as to how they make this
> discrimination and I reckon these are a good start.
>
> At least we are communicating!!!!!!!!!

Communication and controversies feed science. I learn a lot from this
debate. I hope you do not feel like loosing your time and enjoy it too. I am
sure you had to explain your ideas ad nauseum before. That's the main task
of innovative scientists ;) I hope my critics will help improving the
consistency and clarity of your ideas (if required !).

I agree with the evolutionary connection with food and phagocytosis.
However, I stick to my former critics. Let's examine your own post :

> (My) Revised hypothesis 3 (Cunliffe) : (Simply) Clears away spilt
> tissue mess and cells (particularly small) sporting membranes that do
> not have a healthy-self signature.

You replaced the old "self/non self " recognition system by a
"healthy-self-signatures/mess-and-membranes-without-healthy-self-signature"
recognition.

I have absolutely no idea of what is "self" and same with "healthy
signature". A healthy signature is (like a self signature) a purely
metaphysical concept that cannot exist in reality.

Still motivated to communicate with a stubborn virologist ? What do you
think ?
Yours
Pierre








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