polly matzinger (pcm at helix.nih.gov) wrote:
: Hi
: Having just subscribed to the immunology bionet and opeened it
: for the first time, I loved finding a wonderful question from Chris
: Thobur,about the 'real' function of the immune system. Here was his
: question:
: "When recently discussing the actual role that the immune system
: plays, or rather what it does, I have become confused about my personal
: understanding. In school I was always taught that "the role of the
: immune system is to protect self from non-self." How then does
: autoimmune disease occur? Why can neonatal tolerance be established?
: Why can some people receive allo-transplants (solid organ or BMT) and
: achieve tolerance over time? Most obviously, how can the immune system
: be 'trained' to recognize foreign (non-self) antigens as self (as in
: chronic infections)? I'm just throwing these things out for discussion
: in hopes that this group can prove to be more useful than a catalog of
: people asking for the 'reagent of the day."
: Chris Thobur
: The answer, of course, involves explaining the 'soul' of the immune
: system, so here is my attempt. What followss is actually the first rough
: draft of a paper that I have written to be sent to immunology today. I hope
: it answers the question Chris asked and that it generates some more.
: If anyone finds that there are parts that are difficult to understand,
: please let me know so that I can correct them before sending it. It's
: long (ten printed pages) so anyone who wants to read it should probably
: print it out first. I apologize for sending it this way but I haven't
: learned how to add 'attachments' yet.
: Cheers!
: Polly Matzinger
In the interest of bandwidth, I have deleted your article and I hope
if I assume or imply anything that a citation of the text will explain
that you will point it out to me. My comments are pretty general and
for starters I can't emphasize enough how much I appreciate this kind
of revolutionary thinking. If it's not right on the mark, it is certainly
well on it's way.
I am sitting with a copy of your posted article which you stated that
you may submit to Immunology Today and a copy of "The injured cell: the
role of the dendritic cell system as a sentinel receptor pathway" MA
Ibrahim, BM Chain and DR Katz, Immunol Today 16:181. 1995 (the most
current issue as of today). I have also read your extensive review
article in Annual Review of Immunology, May 1994 (which I don't have a
copy handy), but I want comment on the phenomenal degree of overlap in
the ideas expressed by you in both this paper, your review, and in
Katz' paper. Katz' review, in a brief summary, discusses Janeway's ideas
(as you mentioned), but later goes on to discuss a dichotomy between
apoptosis and necrosis and how each affect the immune response in the face
of injury (not unlike your paper).
My first question: Nowhere could I find any reference to necrosis in
the terminology that you used and I am wondering if you have a special
reason for avoiding that term. I suspect so only because the literature
that I have reviewed in regard to cell death has generally presented
the same dichotomy that Katz discusses between apoptosis and necrosis.
Now that's a very black and white way of looking at cell death and
I tend to doubt anything that excludes a gray area. I am wondering if
you too are thinking along these lines?
My next question, if a T cell can function as an APC itself, maybe
professional - maybe not, can a T cell tolerize for its own self
antigens? More specifically, I am not aware that T cells express
B7 (I may be mistaken-let me know), but assuming that they cannot
supply signal 2, but in humans, they can supply signal 1 to another
T cell, and say the antigenic peptide of the MHC:peptide complex on
the T cell surface happened to be an HIV peptide because the cell
was infected, can we say that the T cell is tolerizing the immune
system to HIV? Additionally, I would be interested in any other
thoughts that you have considered with regard to your model in relation
to HIV infection.
My final question: I have come to accept the hypothesis that cancer
is a condition that is experienced by everybody to some extent and
that it does not become a disease because the immune system is responsible
for keeping it in check; i.e. killing cancer cells before they can
take on the formation of a tumor and have pathological consequences.
What are your thoughts on this assertion and how would you apply
your model given that the cancer cell could not provide signal 2 and
therefore would tolerize the T cells rather than undergo a cancer-check
death?
As I think more about your ideas and as the discussion progresses,
more questions will come to mind, rest assured. But thank you for
sharing your ideas. It is a refreshing turn for this newsgroup.
TKendrick
