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

Jamie Cunliffe cunlij at
Sat Feb 12 16:39:38 EST 2000

In article <881qeg$215b$1 at>,
  "Pierre" <sonigo at> wrote:

> 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.

This is a geat point on which to elaborate. In the Eighties the
perception of the immune system was that it learnt the sum total of all
self-antigens at the foetal/neonatal stage. This provided a catalogue
of self Ags so that anything that later turned up later, not in this
catalogue, could be zapped as foreign. Well, if this is that critical,
why are countless invertebrates able to keep excellent control without
this catalogue? When, say, Nato ships, aeroplanes or tanks are in
battle situations, they might well carry personnel who can recognise a
Mig or a Sikorski but they rely more heavily on a radioed "friend or
foe" query. Only "friends" know the current "friend" transmission. It's
likely that invertebrates also use such "friend ID"system. As such it
is a healthy-self-signature. Straight away, your comment that this is a
metaphysical concept implies that the traditional self-antigen/non-self
antigen discrimination is JUST as metaphysical and a lot more complex
and cumbersome. So what OBJECTIVE evidence do we have for this whole-
cell-healthy-self-identity mechanism? Solid, concrete, consistent
evidence in the Tnk cells (Kärre K. "How to recognise a foreign
submarine" Immunol Rev 1997; 155:5-9) and they turn up (just as you'd
expect) in evolution, after "phagocyte/amoebocyte-alone" systems and
before T-cell and anamnestic based systems (jawed vertebrates onwards).
So, to my mind, that strongly supports the contention that the system
was built on healthy-self/unhealthy self (whole cell!!) discrimination.
We already know a lot of things that probably contribute to the
identification of  healthy-self by phagocytes; ligands that inhibit the
C3 like cascade, CD 11 and CD18, CAMs in general including the ICAMs,
(likely) gap junctional communication, electrical synchrony and, I
reckon, other folk could add more meat to this putative list. The Tnk
mechanism probably relies on these (inner evolutionary shells) plus the
new feature of Class I Mhc+peptide identification - you need to read
the "phlogiston"article (my web pages) to realise more detail of what I
am speculating on here.


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