"Danger" or "Alarm"?

Mike Clark mrc7 at cam.ac.uk
Tue Feb 22 14:32:04 EST 2000

In article <88kglg$lag$1 at nnrp1.deja.com>, Jamie Cunliffe
<URL:mailto:cunlij at my-deja.com> wrote:
> In article <38AC84C2.C0BFCAC8 at home.com>,
>   D Forsdyke <forsdyke1 at home.com> wrote:
> > The word "danger" is currently popular among immunologists.
> > However, "alarm" (Forsdyke, 1995) may be preferable, since it
> > conveys the sense of a distinct call to action, whereas
> > "danger" is an attribute which leads one to beware, or keep away.
> I agree that "alarm", as the initiator of any response, is at the
> centre of any inflammatory/immune response. David Lo's group have
> recently published a paper in Immunological Reviews on RelB. It is
> clear that ALL nucleated cells are able to signal alarm. The
> probability is that nearly all inflammatory/immune responses are set
> off by the cells in a previously "happy" tissue realising that
> something is amiss and sending for the "police" (phagocytes and their
> evolvent retinue).
> BUT, once the troops arrive they must set about ingesting, digesting
> and presenting "something" to the T-cells. The main quetions remain, I
> think, "what to ingest?" and what to weight towards immune aggression
> rather than T-cell clonal deletion. I reckon that the decision about
> what is to be ingested is a very ancient discrimination that has
> probably changed little from the free amoebocyte/early multicellulate
> lifeforms.

I would disagree here. I would say that two key recognition systems that
are certainly involved are Fc receptors and complement receptors.
Indeed adaptive immune responses to most protein antigens are greatly
diminished or even non-existant in the absence of the complement component
C3. Both enhance antigen uptake and presentation. 

I am not aware that amoebocytes possess either of these.

> The main thing that has changed in mammals is the elaboration of this
> primitive response to make it faster and give it a memory of "past
> trangressions".
> I am sure that thinking of it in terms of a horror autotoxicus
> to "healthy self" is both phylogenetically and functionally a "front
> runner". It is basically "attack anything that doesn't have a healthy-
> self signature".
> Jamie

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