Jamie, thanks for your explanation. My neurons are less messy ;)
I understand the "mess" tag is attributed to the environment and not to the
antigen.
Do you have a more precise idea (or reference, to keep you from a long
explanation) of how it is possible for a phagocyte from the beginning of
metazoan evolution to recognize mess from non mess, are start different
actions when the mess is messy rather than tidy ?
I read P. Matzinger already (and your papers online too) but I am not sure
this point is treated, except by a "black-box" evolutionary argument : "they
had to do it to guaranty their survival".
Thanks
Pierre
Thanks
Pierre
"Jamie Cunliffe" <cunlij at my-deja.com> a écrit dans le message news:
87nkj4$cls$1 at nnrp1.deja.com...
> In article <87n2eq$mse$1 at news4.isdnet.net>,
> "Pierre" <sonigo at cochin.inserm.fr> wrote:
> >
> > I understood that the self/nonself discrimination is a widely debated
> view,
> > because of some difficulties (schematically, amongst many) :
> > 1) It is difficult to imagine theoretically an accurate mechanism for
> such
> > discrimination, given the diversity of self and non self.
> > 2) It is shown experimentally that the discrimination does not hold
> > (autoimmunity, tolerance, etc.)
> >
> > I do not understand how the replacement of "self/non-self" by
> > "mess/non-mess" solves the two points above, except by making the
> > theoretical fundations of immunology more messy ;)
> >
> > 1) How cells can recognize (are instructed to recognize) mess from
> non mess
> > ?
> > 2) Mess/non mess can explain everything because mess is even more
> difficult
> > to define than self. So we can say anything to fit the theory : ie
> > autoantigens are self but messy, weak antigens are non self but non
> messy,
> > etc.
> >
> > What do you think ?
> > Pierre
>> Pierre
>> It seems to me that you may have fallen straight into the trap of
> traditional thinking. You are talking about non-self and messy
> ANTIGENS. Antigens are not classified as self, non-self, messy or tidy.
> Phagocytes have, from the very beginning of metazoan evolution been
> adept at finding and tidying up tissue (cellular) mess. An infarction,
> an area of crushed cells, spilt cells for a variety of reasons. What is
> more the tissue mess can be divided into "messy mess" where cells spill
> their cytoplasms and "tidy mess" where apoptotic cells are quietly
> removed without any great inflammation. Indeed, so silent and efficient
> is this process that it is only in the last few years that we have
> become aware of the staggering volume of cells that are silently
> removed by adjacent cells and phagocytes - without significant
> inflammation. An analogy is like knowing what is garbage and tidying it
> up in strong plastic bags ready for disposal when the garbage cart
> comes along. "Messy mess" is like throwing it about with gay abandon
> and without any intention to try and package it ready for disposal. The
> colony considers this situation a serious threat. Seeing inside-out
> membranes, spilled Il-1 (not pro-inflammatory when confined inside
> apoptosing cells/bodies), seeing intracellular structures such as
> mitochondia in the extracellular tissues - these are all pro-
> inflammatory. Antigens presented dominantly in this sort of milieu will
> provoke a strongly aggressive anamnestic immune response. It is only
> the paucity of precursor T-cells specific for self antigens that
> dampens aggression to self (because widespread apoptosis tends to mop
> them up into "tolerance"; by elimination or by a positive suppression
> of inflammation - probably just the former).
>> So on your two points
> 1) Phagocytes have been recognising and clearing away tissue mess from
> time immemorial. This is their raison d'etre.
> 2) Mess is easy to define - not only that but we already know a lot of
> the features that characterise it (above). Polly Matzinger has proposed
> that the innate recognition of various bacterial features may, indeed,
> be the recognition of intracellular mitochondria - obligate
> intracellular organisms of bacterial origin. Everything can be looked
> at from another perspective.
>> Jamie
>> --
> Waterside Health Centre, SO45 5WX, UK
> Home pages
>http://www.ndirect.co.uk/~greenprac/jamie/jamie%20main.htm>>> Sent via Deja.com http://www.deja.com/> Before you buy.
