Dr Fuchs wrote
>My conclusion, then and now, is that naive T cells cannot discriminate >self from nonself because they will be rendered tolerant of any >antigen, self or foreign, that is presented exclusively by B cells.
>Now, if there is anyone out there who can refute that reasoning, I >would be happy to accept the possibility that there may be self/nonself
>discrimination by the immune system.
I read the Science papers and the correspondence on the danger theory and am still somewhat confused about self/non-self recognition I would appreciate it if anyone can enlighten me and apologise in advance if this has alredy been discussed here.
I understand that some sort of inflammatory signal may be neccesary for effective immune reponses as Drs Fuchs and Matzinger have noted in the use of CFA to elicit immune responses but this does not address self/non-self recognition, it merely underlines the requirement for a danger signal in addition to non-self recognition.
I've read of a few incidences where self proteins injected in adjuvant induce immune responses but is this the norm or does it reflect the limited quantity of certain antigens in the thymus and thus the leaky nature of thymic tolerance? In the mls superantigen system where deletion in the thymus seems quite clear, are peripheral responses to these antigens detected? I thought peripheral unresponsiveness in this system was well documented thus showing self/non-self discrimination in the periphery.
I don't quite see what difference it makes to self/non-self discrimination of the T cell repertoir in the thymus if antigen presentation by B cells in the periphery results in tolerance. It does explain the concept of neo-natal tolerance and some forms of peripheral tolerance but again this just indicates that effective presentation is required for immune responses to FOREIGN antigens to occur, not that self responses can occur by effective presentation.
I agree with a previous post which suggested that non-self/self discrimination and the danger theory can co-exist. I don't understand why Drs. Fuchs and Matzinger claim that non-self/self recognition does not exist unless responses to self proteins can be commonly observed if a "danger" signal is co-administered. Maybe I've missed something. Maybe I'm wrong and self reactivity is easily induced. If so I'd like to know. If you can explain the danger theory with regard to the above points I would be grateful.
Stephen
Dr Stephen McSorley,
CNRS IPMC,
660, Route des Lucioles,
06560 Valbonne,
France
