[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.