In article <ant101644b49Pk=+ at mrc7acorn1.path.cam.ac.uk>,
Mike Clark <mrc7 at cam.ac.uk> wrote:
> The trouble is that if you try
> to force immune recognition to fit a neat 25 word or less summary your
> bound to get it wrong. Any immune system that declared to the
environment
> how it worked in very simple and easy to follow unwavering rules is
doomed.
> A degree of unpredictability in immune response is almost certainly an
> asset to survival of a species.
Mike
There's a lot of meat to reply to here! Not least in expanding on your
second and third sentences. That is the subject of a maturing file. But
let's stick with "bound to get it wrong". Do you want to wager on that?
Ok, I won't argue that you won't find detail that is wrong. But I will
wager
a) The conventional view is fatally flawed.
b) The system is a morphostatic not an enemy hunting system.
>> What bugs me is just how slavishly some people will adhere to simple
ideas
> even in the face of overwhelming contradictory evidence!
Please tabulate so that I can address.
>> They conveniently forget that you can tolerise a mouse with human IgG
in
> deaggrated form but if you aggregate it or put it into adjuvant the
same
> protein sequence becomes highly immunogenic. The mouses immune system
is
> not 'responding' to the sequence difference of the human IgG but to
other
> properties of the administered preparation.
Once again (see reply to Ian) aggregated proteins are typical of
intracellular disorder or sick self cells. If you had to guess what
typifies sick or spilt cells you'd probably come up with this list.
Aggregated proteins
Lots of HSPs
Inside out membranes
Organelles membranes
Mitochondrial membranes
Nuclear membranes
ECF DNA
Spilt Il-1 (why don't apoptosing cells - with lots of intracellular Il-
1 - stimulate inflammation and immune responses?)
Eicosanoids released in response to membrane damage
I bet you could add a lot of candidates yourself if you have really
understood what I am saying.
An as for adjuvant - if this isn't an infernal mess what is?
Interestingly, mycobacteria have found this approach useful - they have
typified the sorts of things that sends phagocytes into a frenzy of
aggression. They ensure a survival within a least a proportion of the
phagocytes. They go on to invoke a focal a auto-rejective response that
leads to focal anergy (macrophage inhibition factor is probably a
leading factor here). This leads to an encapsulated culture medium
where the phagocytes are paralysed and waiting mycobacteria are on
their marks to cash in. So it's not much wonder that mushed up
mycobacteria in a bit of lipid make a great adjuvant.
Jamie
--
Waterside Health Centre, SO45 5WX, UK
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