In article <37450fec.4620271 at news.club-internet.fr>, Emmanuel-
<URL:mailto:nony at club-internet.fr> wrote:
> On Thu, 20 May 1999 17:58:00 +0900, Greg Adams <gp_adams at fccc.edu> wrote:
>> >Antibodies that react to the antigen binding domain (CDRs) of another
> >antibody are typically called anti-idiotype antibodies. This occurs
> >naturally in people and a chain reaction type of effect can occur with
> >the antibody (#2) that binds to the antigen binding domain of the first
> >antibody (#1), mimicing the original antigen target of the first
> >antibody. The second antibody then can actually initiate an immune
> >response that will recognize the original antigen. Similar strategies
> >are being employed in clinical trials to try to stimulate patients to
> >mount an immune response to tumor antigens.
>> Thank you for your reply. What you are stating is very important, however
> how would you explain the mechanism of anti-D prophylaxis applied to
> Rhesus (-) mother having a Rh(+) child ? In that case, the antigen (Rh)
> is hidden from the immune system by the antibody, to force the absence of
> production of further Anti-D by the mother and not at all to induce a
> much stronger immune response...
A good question...
Some of my research at the moment is directed towards engineering RhD
antibodies so I've given the mechanism of action of prophylactic RhD
administered to RhD -ve women some thought.
Three main mechanisms come to my mind the first two of which are given most
prominence in text books
1) RhD antibodies block the antigen and 'hide' it from the immune system
2) RhD antibodies cause a rapid clearance of RhD +ve red cells from the
circulation and interfere with priming of the immune system.
3) RhD antibodies bound to RhD red cell antigen delivers a negative signal
which feeds back on B-cells through the Fc gamma-RIIb receptor. This would
prevent further production of antibody to an antigen when there is
sufficient in the circulation.
Of course these three mechanisms are not mutually exclusive so all might
contribute. My favourite at the moment is (3).
>> Furthermore, I went through some papers in which they show that they
> can't detect simple IgG dimers in a single patient. Is this a matter of
> level of detection, I don't know ...what are the evidences for
> anti-idiotypes in a single person ? nony at club-internet.fr>
If stable dimers ie high affinity interactions were to occur for IgG then
it would almost certainly result in the rapid clearance of these aggregates
either through Fc receptors or through complement activation and by
complement receptors. Thus they could be being formed continuously but
would not be stable in the circulation. [You could of course check in
animals or patients with deficiencies in Fc receptors or complement].
Evidence for idiotype networks in animals can be obtained from hybridomas
ie within a single spleen cell fusion find both the idiotypes and
anti-idiotypes.
Cheers,
Mike Clark, <URL:http://www.path.cam.ac.uk/~mrc7/>
--
o/ \\ // || ,_ o M.R. Clark, PhD. Division of Immunology
<\__,\\ // __o || / /\, Cambridge University, Dept. Pathology
"> || _`\<,_ // \\ \> | Tennis Court Rd., Cambridge CB2 1QP
` || (_)/ (_) // \\ \_ Tel.+44 1223 333705 Fax.+44 1223 333875
