prions and immune response
Carmen N. Nichols
sarnicol at reading.ac.uk
Sun May 21 07:57:27 EST 1995
On Sun, 21 May 1995, Mike Poidinger wrote:
> JARDINE P <F3CM at UNB.CA> wrote:
> >To those still brave enough to wade through the Ebola posts:
> >I was thinking about prions and the ability of a host to generate an
> >immune response. Is there a detectable antibody titre in hosts which
> >have been exposed to the prion?
> Sometimes. Never very good, if it is there at all.
> >Technically, if the prion is really a rogue cellular peptide, it
> >would not ellicit an immune response since it would be auto-immune.
> >However, if the PrP (Sc) has a different conformation from the PrP
> >(C) as is speculated, would this provide sufficient epitomes of
> >"foreign" appearance for the humoral system to kick in.
I'm afraid I'm getting a bit mixed up over who wrote what so I'll just
plough straight in. I think the problem of there being no immune
response against PrPsc on infection may stem from the physical properties
of PrPsc and the nature of the primary immune response.
1) The primary immune response is a low affinity response and so not
sufficiently fine tuned enough to differentiate between PrPc and PrPsc.
All primary clones, therefore, that recognise PrPsc will consequently be
able to recognise PrPc and so have already been ablated or suppressed.
2) PrPsc may accumulate somewhere along the endosomal-lysosomal pathway
in the cell and is resistant to its proteases. This protease resistance
may preclude PrPsc from immune presentation.
3) There are some immune effects upon infection for example
auto-antibodies against neurofilament proteins are found in many CJD
cases and mRNA encoding TNF and IL's are upregulated late in infection.
Dr. Martin Cann of the Prion Posse (with a little help from MR. Lionel
I'll mail you direct also Mike for a chat.
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