Self/Not-self Discrimination: the basics

Shiv Prasad shiv at tsp.med.umn.edu
Sat Jul 18 12:24:48 EST 1992


In article <92199.175414FORSDYKE at QUCDN.QueensU.CA> <FORSDYKE at QUCDN.QueensU.CA> writes:
>
>    (ii) List possible mechanisms of self discrimination WITHIN
>         organisms. (The latter may be subdivided into EXTRACELLULAR
>         self/not-self discrimination, which is what most immunologists
>         are familiar with, and INTRACELLULAR self/not-self discrimina-
>         tion, which is more controversial.)
>
Since I'm working on my thesis in autoimmunity (Experimental Autoimmune
Uveoretinitis), I can go on and on and on about deletion, anergy, super-Ag
V-beta genes, sequestration, etc. involved in self-nonself discrimination.
Obvoiusly in our model autorx. T cells are not deleted, not anergic, and
use several different V-beta genes, so we're left with utter confusion as
to why this disease is not spontaneous.

That being that, there are other more "primitive" mechanisms of discrinination
that are perhaps equally interesting as T cell tolerance.  These include
the discrimination among sponges, i.e. if the red and green sponges are
made into single-cell suspensions and mixed, chimeric (technicolor) sponges
do not form, rather the red cells aggregate and the green cells aggregate.
Someone correct me if I have the colors wrong (or anything else for that matter)This would seem to be due to different adhesion molecules on the different
?species? ?strains?.

The other mechanism that I can think of is the bacterial restriction enzymes
that recognize foreign DNA due to methylated sequences or sequence patterns.

Since we're all immunologists here (maybe), we tend to think of our own
system as the most exquisite (and generally it is).  But these other forms
of
discrimination are also food for thought.

As far as immunology, an interesting discussion lies in the transgenic
mice expressing foreign MHC on the pancreatic beta-cells.  Although these
mice are tolerant of the transgene product, different lines from different
labs are tolerant in different ways.  Some are tolerant/anergic in vivo, but
the animal's T cells respond to the allo-MHC in an MLR.  Other lines seem
to be tolerant in vivo and also in vitro.  Why the difference?  Is it due
to the transgene, whether it be class I or II?  Is it the level of expression?
Or is there some superAg on the B cells in the MLR that would abrogate
tolerance in one haplotype, but not the other?

Shiv Prasad
Dept. of Microbiology (and Immunology)
Univ. of Minnesota
shiv at lenti.med.umn.edu



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