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

Pierre sonigo at cochin.inserm.fr
Sun Feb 13 07:01:57 EST 2000


"Jamie Cunliffe" <cunlij at my-deja.com> a écrit dans le message news:
884juq$knl$1 at nnrp1.deja.com...
> In article <881qeg$215b$1 at news6.isdnet.net>,
>   "Pierre" <sonigo at cochin.inserm.fr> 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.
>
> Jamie

Jamie,

I fully agree that the current paradigm also is metaphysical. I am not
fighting against your views to defend the paradigm. I just think they are
very similar, and probably both wrong. I am afraid this last sentence will
be treated as a "foe" signal by everybody :)

Thanks for the precisions about possible molecular basis for the "friend or
foe" signal. But we have to admit it is not so clear for the moment. I
really wonder what it is ? Surveillance of what by what ? In a poor simple
and minimal animal like a cell -a bunch of "coordinated" chemical reactions-
who is able to survey who ????

I enclose two stories, inspired by ecology. I hope they are not too long and
will illustrate why I do not like the paradigm, and why I think you are
still very close to it. Their is NO self/non self, NOR morphostatic
surveillance in ecosystems (except for predarwinian biologists, see for
example Linnaeus : "la police de la Nature"), although ecosystems are more
stable and rich of functions than any cell or organism we know.

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

Story 1 : Is it possible to do science when we are in the center of our
observations ?

Mr Immunologist (talking to one of his activated lymphocyte through a new
communication device  he has just designed) : Hello Mr Lymphocyte. Do you
hear me. Please answer. I am testing a new machine.

Mr Lymphocyte : Hi !

Mr Immunologist : MY dear Mr Lymphocyte, I am so thankful for your marvelous
activity. You have been so well instructed during MY development to
distinguish ME from non-ME and to develop efficient mechanisms to defend MY
integrity against aggressive microbes and cancers. I am amazed by the
perfection and complexity of your interactions with MY other cells to build
MY immune system, thanks to evolution that adapted you to MY survival, using
MY complex and finely regulated molecular apparatus. Can you tell me all the
details of your activation status ?

Mr Lymphocyte : Silence, don't you see I am eating !

Mr Immunologist (terribly disappointed) : Please tell me, I promise to
recognize your contribution.

Mr Lymphocyte : You are just a stupid egocentric ecosystem. You are proud to
have consciousness ! What you call awareness of yourself corresponds exactly
to my definition of egocentricity. Does the forest ask how its animal or
vegetal components manage to recognize healthy self signatures and fight for
its existence ?

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

Story 2 : Is it possible to conceive vaccination (the origin of all
immunological concepts) without self/ non self or without healthy self
signature ?

Mr Clearwater (director of the River Health Institute): The river suffers
regularly from a strange disease called redness : it is a red fish
proliferation with multiple pathogenic consequences. Due to rainwater
overflow the fishes are transmitted from a healthy reservoir where they
surprisingly caused no anomaly. When the fishes infest the river, they eat
algae and insects that purify the water. With less algae and insects, the
water is different and other animals and plants in the river suffer from it.
All organs in the river are terribly ill from red fish infection. We have to
protect our rivers from these fishes !


Mr Drugdesign : let's design an antifishotic. To avoid toxicity for other
non pathogenic fishes in the river, we just have to know the exact molecular
structure of the fish mouth, and we can design a poisoned insect that will
specifically fit the mouth of the virulent fish, so the other fishes will
not eat it.


Mr Vaccine : You will poison the whole river ! Bigger fishes will also eat
the poisoned insects, whatever their structure ! I have a better idea. Let's
breed a huge amount of red fishes in our experimental aquarium. We will
anesthetize them slightly, so they will not cause any damage, before
injecting them massively into the river.


Mr Drugdesign : Are you crazy ? Injecting attenuated fishes in the river !
How do you expect this to work ?


Mr Vaccine : That's easy. All the kingfisher birds in the neighborhood will
come and multiply above their usual number this summer given the abundance
and easy capture of their favourite resource. Next year, the greater number
birds will easily control the red fish proliferation.


Mr Drugdesign : I am afraid that you will need to inject fishes regularly to
maintain a sufficient number of kingfishers. We will not waste our time and
money breeding red fishes to feed these birds.


Mr Vaccine : Given the long life expectancy of the birds, I think an
anesthetized red fish boost every ten years will do the job.

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

Regards
Pierre










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