The problem of self/not self discrimination is THE fundamental problem
in immunology and received much attention at a recent forum on "CLONAL
DELETION AND ANERGY: FROM MODELS TO REALITY" (published in Research in
Immunology. volume 143). Workers in the field seem to differ on some very
basic issues. Perhaps a useful role of this Discussion Group would be to
go over some of the basic premises, to see what we can all agree on.
First some background for those not too familiar with the area. When
considering how an organism deals with external or internal predators, it
is axiomatic that there must be a system component (or components) which
can distinguish whether the input signals originate from "self" or "not-
self". Failure to do this may result in death from "friendly fire",
manifest as various diseases of presumed "autoimmune" nature, (such as
rheumatoid arthritis, lupus erythrematosus, etc.).
When you meet someone in the street, there are a variety of ways you
recognize them, perhaps the way they walk, the type of clothes they
wear, or their facial features. If you were a Martian and wanted to
discover how human beings recognize each other in the street, you could
design an experiment to systematically remove each of these parameters
and see whether this interfered in any way with human recognition. For
example a facial mask would eliminate one variable. In order to do this
one must first conjecture, that facial features might be one of the ways
used in this form of discrimination.
So, given that some form of discrimination is occurring (as evidenced
by the phenomenon under observation; in this case meeting in the street),
the problem can be broken down into three parts.
1. List possible ways inwhich discrimination could occur.
2. Design experiments to systemically "mask" each of these and
determine if discrimination can still occur.
3. Having determined the criteria used in discrimination, design
experiments to discover the mechanism.
At this stage I invite Discussion Group participants to do two things:
(i) Comment on this basis agenda or "game plan".
(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.)
Sincerely, Don Forsdyke (Discussion Leader)
Department of Biochemistry, Queen's University, Kingston,
Canada.
