real function, type/tope, tolerance.

Ralph M Bernstein ralph at ccit.arizona.edu
Mon Jun 12 13:17:29 EST 1995


    ok, i lost tkendricks address and post, so here is my reasoning for my
prev response.  

    the reason i emphasize idiotope instead of idiotype is that dr fuchs
seems to be assuming that they are the same thing.  yes, yes, yes, some
bcells may process their ig and present it, but so what? 
     (in my previous posts i reffered to our lab's work showing high
autoantibodies to cdrs, and frwrks in normals, as well as highly increased
levels in autoimmune and virally infected individuals-so _obviously_ i
beleive that a self directed immune response is real) 
    
    what _was_ purported was the presence of presented idiotypes on the mhc,
and this is completely impossible.  idiotopes, on the other hand, may be
possible, but may be unlikely.  since an idiotope is a determinant of the
idiotype, (which is made up of the 3d structure of cdrs/hvrs, and frwrks) 
the 3d strucure is extremely imprnt.  when peptides are linearized this 3d
structure is usually lost.  antibodies and tcrs cannot read, they see 3d
shape.  so a linear peptide being presented is different than an idiotype. 
ok?, ok.
    
    kudos to M Clark for his pointing out that the abo crossreaction may be
a weak example of imm memory to bacteria, but the other examples stand firm,
especially when dr fuchs says that he meant enterobacteriacae (sp?) when
salmonillia is a enterobacteriacea and is gram neg and has a vaccine for-to
me usually an indicator of memory.

>organism, like E. coli, Pseudomonas, Enterobacter, Serratia, etc.  
>Against these organisms I would propose that the adaptive immune system 
>plays no role, and an individual that has survived an infection with one 
>of these organisms has no better chance of surviving a reinfection than 
>the first time around.  This is why I believe that the induction of 
>"costimulatory" molecules by LPS of gram negative bacteria cannot be very 
>useful.

but then to dr fuchs question again

>Just because I cannot think of any way that the immune system can 
>distinguish between idiotypes and foreign antigens does not mean that 
>there is no such mechanism.  Therefore I repeat, can anyone provide me 
>>with an acceptable answer to this question?

     the tcells that are reactive to those identicle epitopes or idiotopes
are deleted in the thymus.  these tcells dont reach the perhiphery to react
with a b cell.  since somatic mutation in tcells tcrs is still only
preliminary  (the germinal centre/pcr nature paper) so, in effect they dont
have to distinguish.  the theoreticle v(d)j recombination number is not
reached in the perhiphery, because these are deleted.  b cells, that are
overstimulated, are often deleted (the too-many-nails-in-the-coffin theory)
and this can be a mechainism to stop overstimulated, crossreactive b cells.  

>My answer, by the way, is that T cells can in fact not distinguish, that 
>B cells always tolerize naive T cells, and that the consequence of this 
>is that the immune system cannot distinguish self from nonself because 
>any antigen, self or foreign, presented by a B cell will tolerize naive T 
>cells specific for that antigen.

    AAAAnd so what if the bcell tolarizes _one_ of these tcells?  you have
to see some tcell agonist/antagonist data before you can make the assumption
that all those reactive tcr subsets are gone.  if a perphiral bcell
tolarizes _one_ tcr subset you can have a single aa change in the tcr (in
the cdr _or_ the frwork) and have a different response-ie _no tolerance_. 
(see the nails in the coffin idea).  you can have a whole variety of tcells
out there that -just like crossreactive bcells- that respond to basically
the same aggretope (mhc presented peptide 3d shape) and either be
stimulated, tolerized, anergized and or just ligated.  see recent science
article on tcr agonists antagonists.  the tcr isnt as dumb as is often
thought.  differential signals can be processed thru even the same tcr-so
different responses to that same "tolerizing" bcell can be expected.  so i
dont think that your answer has taken all the factors into account. anyway,

 regards, ralph



   
    
Ralph M. Bernstein
Dept of Micro/Immuno
University of Arizona
Ph: 602 626 2585
Fx: 602 626 2100



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