OBJECT-ORIENTED SIMULATION OF HIV-AND CNS/HIV-INFECTION. Acquired Immune Deficiency Syndrome (AIDS) is the ultimate consequence of a multi-faceted disease process caused by infection with the Human Immunodeficiency Virus (HIV). Due to a selective tropism of HIV for the cluster designation 4 (CD4) receptor population, infection involves both the immune system and the nervous system. Progressively evolving degenerate conditions in both systems render the host increasingly susceptible to """"""""opportunistic"""""""" infections, with a high mortality rate. Previous clinical studies have indicated that at least three critical events are involved in the pathogenesis of AIDS. The first is viral infection of helper T lymphocytes and monocytes early in the course of the disease, the second is the contribution of inductive signals from both cell types to disease progression, and the third is the transport of HIV into the brain by infected monocytes. These observations lead us to pose two questions: (1) how does the dynamics of HIV-infection depend on the dynamics of communication between these central cell-types and, (2) how can selective, i.e. local, changes in this dynamics cause a global alteration of immune function? We will approach these question by studying helper T cell-macrophage interaction and the resulting cytokine production as well as stress-related immunomodulation in the context of a novel computer- experimental system that we developed previously. This system allows the prediction of long-term behavior in the normal and diseased immune system. We will specifically evaluate the production of cytokines Interleukin 1 (IL-1), IL-2, IL-5, Tumor Necrosis Factor (TNF), Neuroleukin (NLK) and Interferon gamma (y-IFN) associated with a single infection (HIV), multiple infections (HIV + other antigens) and neurological stressors. These experiments are designed to distinguish between reversible and irreversible effects of a progressive regulatory disease leading to a degenerative disease in distributed cellular systems. We expect to identify models for therapeutic intervention in concert with on-going experimental and clinical investigations.
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