tumor immunology

John Barton jjb at watson.ibm.com
Wed Sep 21 12:20:42 EST 1994

Perhaps someone will indulge me while I try to decode this

In article <35lvb5$gfh at jhunix1.hcf.jhu.edu>, ejf at welchlink.welch.jhu.edu (Ephraim Fuchs) writes:
|> Recently someone asked about the concept of immunosurveillance of cancer, 
|> to which I replied that I didn't think the immune system could survey the 
|> body for the development of malignancies because tumors arise from 
|> tissues that cannot deliver costimulatory signals for the activation of 
|> naive T cells.
|> This response provoked two questions:
|> 1) What about "cross-priming"?
|> 2) What if such tissues were infected by viruses?
|> Sorry I didn't answer earlier.  I have been having trouble posting.
|> Here are my answers:
|> 1) As small tumors grow, they tend not to shed tumor-specific antigens.  
|> If they do, they do so in small amounts, and the cells that are best 
|> suited to picking up low concentrations of antigen are antigen-specific B 
|> cells, 
   Ok so far: antigen-specific B cells exist in high concentrations, having
been created as a result of exposure to antigens in the past.

|> which are also tolerogenic APCs for naive T cells.  
   Here I am lost.  Tolerogenic antigen presenting cells is all my decoding
ring gives.  Whatzat?  How can an antigen-specific B cell have a role
in increasing immune system tolerance for an antigen its not specific for?

|> By the time a 
|> tumor has outgrown its blood supply, it has already tolerized all tumor 
|> antigen-specific T cells and so there is no cross-priming.
|> 2) I believe that a virus that infects a non-professional APC and does 
|> not cause any tissue destruction will either go undetected by the immune 
|> system or render it tolerant.  Only those viruses that cause destruction 
|> will allow "professional" APCs to pick up viral antigens to incite an 
|> immune response.  

  Hmm...I don't know what non-professional and professional means, but I 
understand that if a virus destroys a cell then there will be lots of debris
around to trigger immune response.  The converse does not make sense to 
me: I thought that a virus could (sometimes) decompose in a cell, be digested,
and keys protein components could end up being presented on the cell surface
to trigger T cell action.  Are you saying that this cannot happen in special
tissue prone to cancer tumors?

|> This is a good mechanism by which the body can pick up 
|> useful genes without the immune system trying to eliminate them.

  Whoa, you mean that failure to decompose and present virus might 
be an evolutionary adaptation that allows certain cells to incorporate
virual genetic material?


John J. Barton        jjb at watson.ibm.com            (914)784-6645
H1-C13 IBM Watson Research Center P.O. Box 704 Hawthorne NY 10598

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