Date: Wed, 19 Jan 1994 12:48:02 +0000
From: p_travers at icrf.icnet.uk (Paul J Travers)
Reply-to: p_travers at icrf.icnet.uk (Paul J Travers)
To: "bionet.immunology mail newsgroup" <bionet-news at daresbury.ac.uk>
Subject: Re: Something unknowable in immunology? Simple logic?
>First, letUs leave aside the caveat that for T cells, any antigen
>encountered after puberty will meet predominantly mature T cells and will
>not generate the first of these mechanisms, since we have to be able to
>account for responses in juveniles with active thymi. I can think of a
>number of factors that would account for the fact that ( pur si muove) we
>can discriminate self from nonself, or at least from potentially pathogenic
>nonself. Whether they constitute the Rother levels of organisation in the
>immune systemS to which Coutinho refers, I leave to others more
This raises aquestion I have often wondered about.. namely why is so much made of
neonatal/juvenile tolerance induction? I can see that the rate of antigen experience
by T cells is greatest when younger, but this ignores the fact that new TcR and Ig are
generated right up until the day you die. Since antigen receptor generation is
essentially a random process it is inevitable that cells with self-reactive receptors will
emerge from the bone marrow all throughout life. If the thymus involutes after
puberty, where are all these new cells getting their education (both in +ve and -ve
selection)? Is the thymic remnant sufficient for the job or do we rely on mechanisms
of peripheral tolerance after puberty? Since the situations of continual antigen
experience and the generation of new receptors continues for a life time, why is the
young thymus so important? (apart from the fact that it works this way in
> Thirdly, pathogens are often capable of non-specific stimulation of the
>immune system; macrophages, B cells and probably T cells have receptors for
>bacterial cell wall components (LPS, mannans) that are able to activate the
>cell, and in the case of B cells and macrophages can induce costimulator
>expression; these cells will now activate rather than anergise.
>Gamma/delta T cells and NK cells may play a similar role in responding to
>viral infections (there is a report of a patient with an NK cell defect
>with acute sensitivity to viral infection), in the case of NK cells most
<probably through the production of interferon. I could go on at length but
<the short answer is that the immune system may be able to recognise
>pathogens as nonself because they tell it they are.
If this is the mechanism though, would bugs not have evolved to mutate away their
LPS like activities, or are they essential for survival (like the MMTV superantigens
are proposed to be)?
>Finally, it may be important for the immune system not to respond to a
l>arge number of innocuous environmental antigens, pollens, food antigens,
>commensal (nonpathogenic) bacteria in the gut and it is here that the
>question of tolerance by non-self antigens may be most important. Of
>course, this gets us back to the discussion of mucosal tolerance and the
>other current thread .....
.....and a new thread about how parasites may do just this?
Dr. Colin R.A. Hewitt
University of Leicester/MRC
Centre for Mechanisms of Human Toxicity
PO Box 138
Phone +44 (0)533 525587
Fax +44 (0)533 525616
E-Mail crah1 at le.ac.uk.