Control in the immune system

[From Mike Acree (980417.1345 PDT)]

Disclaimers: No claims are implied in the following that anyone in the
universe is doing PCT research. Nor is there call for a PCT
interpretation. And if none of the following makes any sense, it's
because I'm trying to digest technical material completely outside my
field.

But I found it interesting recently to hear AIDS interpreted as a
disruption of homeostasis in the immune system. The traditional
assumption, that AIDS results from HIV killing T cells, confronts
several problems. One is that the virus doesn't exist in sufficient
numbers, given the regenerative capacity of the immune system. The
necessary cytopathy has been observed only in vitro, and only in
concentrations much higher than found in vivo--from which Duesberg
famously concludes that HIV is not the cause of AIDS. Ascher and
Sheppard (references follow) propose, however, that HIV operates
essentially by mimicking T cells, leading to a gradual decline in their
production. More specifically, if still simplistically: T cells
recognize antigen only in the presence of self MHC (major
histocompatibility complex) molecules (this may be a mechanism for
limiting immune response to the affected area, rather than flooding the
whole system with lymphocytes); the virus envelope glycoprotein binds to
the CD4 molecule of the T cell in a way that mimics the MHC molecule,
with resulting generalized, uncontrolled lymphocyte activation
("panergy"). Immunologic responsiveness declines because the activated
T cells "do not respond to further stimulation" (S-R at the cellular
level :-)). The decline in actual T cell count is due to a further
process: normally some T cells differentiate into "memory" cells at the
end of the immune response, but the continued activation by HIV prevents
the generation of memory cells ("imnesia"); the "false positive" signals
lead to a gradual decline in T cell count.

The homeostatic model makes sense of some additional puzzles of AIDS,
such as the fact that the T cell decline is gradual rather than abrupt.
It is a model in the sense that simulations have been run, though they
are not yet published. Equations and simulation data for the failed
cytopathic model are presented in the third reference below.

Ascher, M. S., & Sheppard, H. W. (1988). AIDS as immune system
activation: A model for pathogenesis. Clinical and Experimental
Immunology, 73, 165-167.

Ascher, M. S., & Sheppard, H. W. (1990). AIDS as immune system
activation. II. The panergic imnesia hypothesis. Journal of AIDS,
3(2), 177-191.

Anderson, R. W., Ascher, M. S., & Sheppard, H. W. (1998). Direct HIV
cytopathicity cannot account for CD4 deline in AIDS in the presence of
homeostasis: A worst-case dynamic analysis. Journal of AIDS, 17(3),
245-252.

[From Bill Powers (980418 MDT)]

Mike Acree (980417.1345 PDT)--

But I found it interesting recently to hear AIDS interpreted as a
disruption of homeostasis in the immune system. ...

Interesting. HIV mimics a perceptual signal that matches a reference
signal, so no action (such as producing more T cells) is necessary ??

Sigh. So much to do, so few people doing it.

Best,

Bill P.

[From Mike Acree (980420.0828 PDT)]

Bill Powers (980418 MDT)--

But I found it interesting recently to hear AIDS interpreted as a
disruption of homeostasis in the immune system. ...

Interesting. HIV mimics a perceptual signal that matches a reference
signal, so no action (such as producing more T cells) is necessary ??

Yes, that was my understanding, and why I found it interesting.

Sigh. So much to do, so few people doing it.

You may have noticed from the references that Ascher and Sheppard
proposed their homeostatic theory 10 years ago; but they had to wait
this long for the science to develop to a point where some of the
parameters could be specified quantitatively to test the model. In the
meantime, you may not be surprised to hear, their theory attracted very
little notice from the traditional direct-killing crowd. Perhaps the
trajectory of their theory (and of PCT?) will duplicate that described
by Ted Nelson for hypertext, which he invented in 1974. He says: "I
thought it would catch on like wildfire. I was right; it's just that it
caught on like wildfire 20 years later."

Mike