Self/nonself discrimination

KTano ktano at
Mon Jul 18 21:43:08 EST 1994

In article <308fu0INNcre at>, ejf at
(Ephraim Fuchs) writes:

">One of the cardinal features of the immune system is its ability to 
discriminate self from nonself.  Recent experimental evidence suggests 
that a two signal model of lymphocyte activation is the biological basis 
for S/NS discrimination.  For CD4+ T cells, signal two is delivered by 
the antigen presenting cell.

Here is the question:

Since antigen presenting cells take in antigens randomly from their 
environment, how is their delivery of signal two regulated so as to 
achieve a self/nonself discrimination?"

Is this a trick question?I would assume you agree with Polly Matzinger's
suggestion that co-stimulation by the APC is upregulated by "danger"
However, I believe there may be other features that distinguish self from
non-self and can be exploited by the initiating APC. For example, many
microbes such as bacteria and yeasts carry cell walls containing
oligosaccharide moieties such as mannans and glucans not found in self
proteins. Macrophages and neutrophils have mannose and/or beta-glucan
receptors that are used to phagocytose such organisms as part of the
innate immune system. Mannose binding protein, produced in the liver,
serves a similar purpose and natural antibodies could also be important.
So self/non-self discrimination on the part of the APC is possible, at
least for many potentially pathogenic organisms, although, I agree, that
viruses pose a greater problem. There, the APC may need to recognise
stress signals put out by infected cells ("danger").
Ktano (aka, Caetano Reis e Sousa, NIH, Bldg. 10, Rm 11D15, Bethesda, MD

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