In article <36963186.4075003A at uia.ua.ac.be>,
Dear Viggo:
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
vigor at uia.ua.ac.be wrote:
> Hi,
> 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
> molecules.
> 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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