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

Jamie Cunliffe cunlij at
Fri Feb 11 08:36:49 EST 2000

In article <880qur$1edi$1 at>,
  "Pierre" <sonigo at> 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.


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
> 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
> realized it just replaced the previous classification/recognition of
> antigen (self/non self) by a classification/recognition of the
> (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!!!!!!!!!

Regards, Jamie

Waterside Health Centre, SO45 5WX, UK
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