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

Jamie Cunliffe cunlij at
Fri Feb 11 16:44:23 EST 2000

In article <ant111538f7fPk=+ at>,
  Mike Clark <mrc7 at> wrote:
> We are not necessarily talking about how it evolved but about how the
> immune system is used by higher organisms now.


But that it a point that I have been making. The general presumption is
that the system has altered over the course of evolution; that it has
been substantially modified. I am convinced that it has not. It starts
with a simple system of wandering phagocyte/amoebocyte cells that go
around ingesting anything that looks "out of order". These cells
simultaneously involve themselves in encouraging regeneration of any
lost tissues (macrophages still carry out this function in mammals). To
do its job effectively, it has to recognise "mess" of various
constitution - but, importantly, damaged self tissues make up a large
proportion of this "mess". All that has happened in mammals is that the
system has bolted on a memory (the T-cell system) that makes the
accumulation and activation of phagocytes more rapid and responsive.
The two prime principles remain. Phagocytes (APCs in mammals) decide
what is mess and ingest it. Without ingesting it, no cell mediated
immune response occurs.  Without presenting it no cell mediated immune
response occurs. It is the APC that pulls the aggressive anamesis
trigger. Once the T-cells are clonally expanded they are able to
trigger a potent inflammation on re-encounter (Nb, OF APC INGESTED AND
Mhc PRESENTED PEPTIDE). The phagocytes then get down to their ancient
task of clearing up the mess - but they have now been switched into a
frenzy of eagerness to get on with this job. The Tc cells system simly
encourages cells that didn't shut down in a controlled fashion on last
encounter to be more prone to enter the apoptotic cycle on any fresh

> If I have immunoglobulins with specificity for a pathogen and then
when the
> pathogen enters the body the antibodies form an immune complex with
> pathogen where is the disorder that the antibodies recognise?

I am not certain what is in your mind here. However, if you consider
what complement is doing it can be split into the "opsonisation" bit
and the "perforation" bit. The former is more ancient, the second
likely to be a later adaptation and bolt on addition of the perforin
Tc/Tnk mechanism so that it links this onto the opsonisation bit. C3
has a pretty promiscuous attraction for membranes and their proteins.
Much organic stuff attracts the onset of the cascade. Healthy self
cells are protected by sporting protective ligands and secretions that
divert the C3 cascade away from opsonisation and perforation.
Essentially, therefore, complement is a mess (other-than-healthy-self)
marking system. Antibodies are just a cunning way of focusing the
attention of this ancient system onto previously remembered
extracellular debris. IgM probably evolved with the need to clear
extracellular debris when auto-rejection threatened run out of control -
 but you would have to read and understand my papers and
the "phlogiston" article if you are to follow that argument.

> Yes but aggregated antibodies are not typical of intracellular
> they are typical of immune complexes with pathogens!

I have made a gross faux pas here in reading one thing and interpreting
another - so anything I said earlier was irrelevant. I had in mind
aggregated antigen not antibody. I simply presumed. My apologies. I
have no current suggestions.

Waterside Health Centre, SO45 5WX, UK
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