Can apoptotic cells represent "danger" to the immune system?
Geoffrey M Thiele
gthiele at ix.netcom.com
Tue Feb 2 14:53:50 EST 1999
I read your post about apoptosis and the danger signal. I believe that you are right in accessing a distinct
discrepancy in apoptosis and the danger model as Dr. Matzinger has presented it. Her fairly recent publication
in Seminars in Immunology (Oct. 1998: Innate Sense of Danger) deals with apoptosis a bit more:
"...though apoptotic cells may signal a neighboring scavenger, these signals do no induce expression of co
stimulation on APCs."
Later in this paper she describes the more relevant issue when it comes to apoptotic cells in my experience.
Danger can involve cells dying bad-traditional apoptosis that normal cells undergo usually does not fall into this
category, but there is apoptosis that could be considered "bad dying". For example, toxins can cause a mixture
of apoptosis and necrosis and be a danger signal. Dr. Matzinger states in the paper that toxins and pathogens
can induce an immune response (and foreigness of the molecule is a moot point). Therefore, true apoptosis
may not induce immune responses, but toxicity or pathogens. This may explain why influenza in the articles you
mention induce an immune response-it may be the influenza that causes the danger and apoptosis is the
mechanism by which the cells are always taken up. It may be that the danger signal tags the apoptotic cell
differently to induce the immune response.
I would be interested if you see things any differently. Take care.
Monte S. Willis
University of Nebraska Medical Center
Experimental Immunology Laboratory
(402) 346-8800 Ext. 3735
(402) 449-0604 FAX
>In article <36963186.4075003A at uia.ua.ac.be>,
> vigor at uia.ua.ac.be wrote:
>> I'm a PhD student who is very interested in the field of immunology.
>> Recently, the cross-priming pathway by which acceptor professional APC
>> (= dendritic cells; DC) acquire antigen from donor cells to elicit an
>> antigen-specific CTL respons has been studied in detail by the group of
>> N. Bhardwaj et al. (Nature 1998; 392: 86-89 & J Exp Med 1998; 188:
>> 1359-1368. This group demonstrated that the cross-priming phenomenon can
>> be explained by the phagocytosis, processing and presentation of
>> antigens derived from apoptotic and not necrotic cells on MHC class I
>> Well now, my question is how this theory fits with the "danger" model of
>> P. Matzinger (Ann Rev Immunol 1994; 12: 991-1045)? According to
>> Matzinger, the DC must become activated through a danger signal
>> (necrosis, viral infection,...) in order to function as a professional
>> (effector) APC capable of activating virgin T cells. As I understood
>> from this latter model, apoptosis does not represent "danger". Is
>> something wrong with the way I look at these models or is there a
>> distinct discrepancy?
>> Any suggestion?
>> Viggo VT
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