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

Mike Clark mrc7 at cam.ac.uk
Thu Feb 10 07:25:56 EST 2000


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
  `    ||  (_)/ (_)  //    \\ \_   Tel.+44 1223 333705  Fax.+44 1223 333875





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