Biology 446    Unsolved Problems Fall 2011


"Recognizing Self?" Does this phrase mean one thing rather than another?

If a series of words has the effect of satisfying people's curiosity about how something works, but doesn't actually convey correct information about the mechanism by which it works, and especially if it can easily be misinterpreted to support some fundamentally different and non-existent mechanism, then…

Is the series of words WRONG?

Is the series of words MISLEADING?

Is the series of words CORRECT, in that one of the several different ways that the words could be interpreted does match the actual, true mechanism?

In particular, the reason that none of my B-lymphocytes attacks the type A blood group substance is now believed to be because of the past elimination (by the tolerance mechanism) of all those lymphocytes in which VDJ recombination produced binding sites that fit the type A blood antigen (which is a certain polysaccharide, incidentally), or any of my other antigens.

The evidence for this explanation is very strong, except that nobody knows the mechanism of elimination of all those various billions of lymphocytes which would produce "anti-self" binding sites. We can now be sure of this combination: (I) random generation, then (II) selective elimination (so as to produce tolerance), later followed by (III) selective amplification (in response to vaccination, etc.)

A very different way that the same goals could have been accomplished would be for all the cells of my body to have something equivalent to an identification badge, and for the lymphocytes to attack any cells that don't have this identification, or have the wrong kind of identification badge. I stress that this definitely IS NOT how immunity works. But it is what lots of people guess. Many assume that histocompatibility antigens are these "badges". As a guess, that is not unreasonable. It just isn't true.

If someone is told that my blood cells don't get attacked "because the lymphocytes recognize them as self" many or most people will guess ID badges are how it works.

Few people will interpret "recognize as self" as meaning "because the anti-self ones all got killed, & don't exist".

Would we want to say that anti-A lymphocytes detect the A-antigens on my cells, and based on that recognize that they, the anti-A lymphocytes, don't exist anymore.

Please be prepared to discuss your opinion as to whether the meaning of a sentence is whatever interpretation most people will conclude based on that sentence. If a person speaking or writing a sentence means (wants, intends) people to conclude some different meaning (different from whatever most people actually will conclude) then who is wrong? Did the listeners make a mistake interpreting? Did the speaker or writer make a mistake in ambiguity or being misleading?

My belief is that exactly this kind of verbal confusion is why there are no cures for MS, lupus or cancer.


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