New Immune Theory

Dr M.R. Clark mrc7 at cus.cam.ac.uk
Wed Apr 12 08:54:31 EST 1995


In article <3metee$oil at cisunix1.dfci.harvard.edu>,
Ian A. York <york at mbcrr.dfci.harvard.edu> wrote:
>	I'm in the process of reading Dr. Matzinger's article in ARI - so 
>if my question is answered in that I apologize.  If it's "danger" rather 
>than "foreignness" that's recognized by the T cell system, would you 
>expect a cytotoxic response to innocuous antigen - e.g. the CTL responses 
>that are seen to the DNA vaccination protocols and which have been 
>reported in response to certain (killed) vaccines?  Similarly, are the 
>CD4 responses to ovalbumin and other soluble and harmless antigen expected?

One of the big problems with vaccine development is in fact the difficulty
in getting an immune response to the chosen antigens. In experimental
systems in animals it is commonplace to generate immune responses by using
adjuvants etc. These are likely to cause damage and attract the innate
immune system and hence get the ball rolling. In general immune responses
to soluble antigens administered i.v. are very poor.
What this whole argument is pointing to is the key role for the innate
immune system to recognise early features of infection and tissue damage
and then to recruite the adaptive immune response. In this role we need
to consider the receptors possesed by macrophages, neutrophils and NK cells.
>
>	My first response to the proposed change of attitude is that it 
>does not, as such, answer more questions that the foreignness approach.  
>That is, it does address some of the points on which the tradtitional 
>approach is weak, but the converse is also true.  
>
>	But I should finish my reading first . . . 
>
I guess my problem is that I don't find these new ideas that startling. 
Then again I was bombarded by Polly's continuing questioning of immunological
dogma at a time when I was first learning immunology. It's really in the 
semantics of the arguments that the problems lie. It's very easy to explain
a simplified version of the immune system to undergarduate students 
in terms of a self non-self recognition. The problem comes when it's pointed
out that we fail to make immune responses to the vast majority of antigens
to which we are in frequent contact but which are not-self.


Mike Clark, mrc7 at cam.ac.uk          http://www.path.cam.ac.uk/MikeClark/
--
  o/ \\    //            ||  ,_ o   Mike Clark, C.U. Dept. Pathology
 <\__,\\  //   __o       || /  /\,  "to pay for my hobbies I teach
  ">    ||   _`\<,_    //  \\ \> |  immunology and engineer antibodies :-)"
   `    ||  (_)/ (_)  //    \\ \_ 



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