In article <38A20F8F.1837C940 at home.com>, D Forsdyke
<URL:mailto:forsdyke1 at home.com> wrote:
> Holger Fehr wrote to Jamie:
>> > I would agree that Polly Matzinger's "danger" model is worth to be
> > discussed in a wider public. It therefore might be usefull if you would
> > us give > some citations on the original and some newer articles on
> > that topic.
>> Hello,
> BEFORE we all go rushing to the literature, why not do
> a bit of thinking? What is "danger"? It is a word applied when
> one has a certain sort of information about something. For example,
> as you approach a sunny beach you might be confronted with a sign
> saying "DANGER. LAND-MINES". In order to write that sign, someone
> had to discern that among the objects on the beach there were some
> compatible with humans (sand, pebbles, weed), and some incompatible
> ("land-mines").
>> Thus, first there was a binary discrimination event. The
> decision to use the "D-word" either followed or did not follow
> this event. In biological systems, a convenient nomenclature
> for this binary decision-making process is that it involves
> discrimination between "self" and "not-self".
>> The ability to carry out this discrimination is SO important
> that it is likely to have arisen among the very first living forms
> (unicellular). The mechanisms which evolved there may then have been
> modified and adapted when multicellular organisms arose.
>> That's enough for a start. NOW let's go and read the literature!
> For a start we could do worse than visit the web-site below.
>> Sincerely,
> Donald Forsdyke. Discussion Leader. Bionet.immunology
>http://post.queensu.ca/~forsdyke/cancimm1.htm>
No don't go to the literature! Pick an example and discuss!
OK I'm interested in antibodies so I'll pick them as an example.
The clonal selection hypothesis says that every clone of B-cells has a
unique specificity(ies) as a result of a unique immunoglobulin sequence.
All of my B-cell clones are self though aren't they? So obviously I want to
be tolerant of them all don't I? And we are tolerant of self right? After
all, we all believe that self not-self IS the basis for immune recognition
don't we?
;-!
Ok so if that were the case then every clone of B-cells would have to
tolerise all of our T-cells to avoid self recognition? Does this happen?
Are we tolerant of all self immunoglobulins?
Quite a few companies are prepared to pay millions of dollars in royalties
for 'fully human' or 'humanised' antibodies because they believe the above!
Even though I published several of the papers that persuade these companies
to shell out millions I'm not sure that I believe that we are tolerant of
all self V-regions.
Is there an alternative view?
Well I wonder if perhaps we only bother to respond to 'Dangerous'
antibodies?
I think this is more likely.......
Then we can argue about what makes one antibody look 'Dangerous' and
another 'Harmless'. I have my views on this.
Danger / No danger does help you to visualise the problem differently to
Self / non-self as long as you don't get distracted by the semantic
arguments.
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
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