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

Jamie Cunliffe cunlij at
Sat Feb 5 17:13:28 EST 2000

In article <389C4454.851B9936 at>,
  D Forsdyke <forsdyke1 at> wrote:

>   Try this. Disorder is when something "not-self" happens. "Not-self"
> may be a foreign bug, or "self" that has gone sour so that it is now
> same as "not-self". Are we just using different words to describe the
> same thing? Ultimately, we have to get down to the chemistry so that
> can understand why "disorder" and "not-self" can be equated.

New perspectives are usually about describing the same facts in
different words. What you are saying here seems to me to be pretty much
the same as the concept of (whole cell)-healthy-self and (whole cell)-
other-than healthy-self.  And, yes, ultimately, we might be able to get
to describe what is happening at a quantal level, let alone a chemical
level; but until that is possible a more analogous model is helpful.

You have (earlier) implied a need for internal cell surveillance - a
process whereby individual zygote-derived-cells monitor their own
internal health. Now, David Lo's group have come up with some objective
facts that support this contention strongly (Immunological Reviews 169
p225, 1999, Integrating innate and adaptive immunity in the whole

What I believe we must do is to escape from this old idea that antigens
are divided into self and non-self (the foeatal/neonatal imprinitng of
self ) and that there is a horror autotoxicus to self antigens. Far
from avoiding attack on self antigens the system is as happy to use
self antigens as it is to use foreign antigens when they are presented
in a stressed/messy presentation (disordered presentation). It is only
the fact that the lymphocyte pool has been greatly depleted of self-
reacting lymphocytes simply because of the mass apoptosis (controlled
shutdown) that goes on constantly in the body. The vast mass of self
cells that become disordered sense the crisis internally and do the
decent thing by apoptosing. I repeat below a paragraph from my web

The whole process works through differential rates of cell death.
Irremediably dysfunctional cells are expected to do the decent thing
and die early by trashing their cytoplasms. In the process, they
sanitise their contents. The fact that infection is a frequent cause of
intracellular dysfunction is of no interest to the system. Cells don't
think 'I am - or you are - infected'. They realise 'I am - or you are -
irrecoverably sick'. The corollary is that there is a differential
nurturing of healthy-self-cells that are in junctional communication
with their neighbours. The adaptive 'immune system' simply remembers
some caricature of those cells (or their debris) that failed to do the
decent thing last time and it then watches out for similarly
caricatured cells (and their debris) the next time round.

The real problem is the old, simplistic way of assuming that the system
categorises antigens into self and non-self. This is, I contend, plain
wrong and wildly misleading. An organism that doesn't cause stress or
make a mess (create disorder) doesn't provoke any aggressive responses
to its antigens.

I am content that this presents a fundamentally different perspective
from seeing the system as a "bug hunting system".  We need to
vigorously exorcise this idea that the system is looking for bugs. OK,
it latches onto the most unusual antigens associated with the mess left
by PATHOGENS (which, by definition make a mess); this is not in
dispute. This leads to the illusion that the system is a discriminator
of self from non-self. I contend that it is not!

Waterside Health Centre, SO45 5WX, UK
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