The immune system is dead! Long live the immune system!

Mike Clark mrc7 at
Thu Feb 10 07:25:56 EST 2000

In article <38A20F8F.1837C940 at>, D Forsdyke
<URL:mailto:forsdyke1 at> 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

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'

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

Mike Clark,                        <URL:>
 o/ \\    //            ||  ,_ o   M.R. Clark, PhD. Division of Immunology
<\__,\\  //   __o       || /  /\,  Cambridge University, Dept. Pathology
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