http://hdl.handle.net/2027.42/78392 Mon, 13 May 2013 20:41:01 GMT 2013-05-13T20:41:01Z http://deepblue.lib.umich.edu:80/bitstream/id/279984/216680.gif http://hdl.handle.net/2027.42/78392 http://hdl.handle.net/2027.42/83698 Role of the Thymus in Pediatric HIV-1 Infection Kirschner, Denise E.; Mehr, Ramit; Perelson, Alan S. Several lines of evidence suggest that HIV-1 is present in the thymus during HIV-1 infection. Precursors to mature CD4+ T lymphocytes develop in the thymus, which suggests that thymic infection may play a role in the CD4+ T-cell decline observed during the course of pediatric HIV-1 infection. We illustrate, through mathematical modeling, the potential effects of thymic infection on the course of pediatric AIDS disease progression. We find that infection in the thymus not only can supplement peripheral infection but can help explain the faster progression in pediatric cases, as well as the early and high viral burden. Thu, 01 Jan 1998 00:00:00 GMT http://hdl.handle.net/2027.42/83698 1998-01-01T00:00:00Z http://hdl.handle.net/2027.42/83697 Immunotherapy of HIV-1 Infection Kirschner, Denise E.; Webb, G. F. A number of lines of evidence suggest that immunotherapy with the cytokine interleukin-2 (IL-2) may boost the immune response to fight HIV infection. CD4+ T cells, the cells which orchestrate the immune response, are also the cells that become infected by the HIV virus. These cells use cytokines as signaling mechanisms for immune-response stimulation, growth, and differentiation. Since CD4+ T cells are hampered due to HIV infection, normal signaling, and the resulting cascade, may not occur. Introduction of IL-2 into the system can restore or enhance these effects. We illustrate, through mathematical modeling, the effects of IL-2 treatment on an HIV-infected patient. With good comparison to existing clinical data, we can better understand what mechanisms of immune-viral dynamics are necessary to produce the typical disease dynamics. Thu, 01 Jan 1998 00:00:00 GMT http://hdl.handle.net/2027.42/83697 1998-01-01T00:00:00Z http://hdl.handle.net/2027.42/83672 Dynamics of co-infection with M. tuberculosis and HIV-1 Kirschner, Denise E. Since 1985, there has been a renewed epidemic of tuberculosis (TB) that was previously thought to be in check. There is evidence to believe the main factor for this resurgence has been the human immunodeficiency virus (HIV). Co-infection with HIV and M. Tuberculosis has profound implications for the course of both diseases. This study represents a first attempt to understand how the introduction of an opportunistic infection, namely Mycobacterium tuberculosis, the bacteria that causes TB, affects the dynamic interaction of HIV-1 and the immune system. We create a mathematical model using ordinary differential equations to describe the interaction of HIV and TB with the immune system. It is known that infection with TB can decrease the CD4 + T cell counts a key marker of AIDS progression; thus, it shortens survival in HIV infected individuals. Another main marker for HIV progression is the viral load. If this load is increased due to the presence of opportunistic infections, the disease progression is much more rapid. We also explore the effects of drug treatment on the TB infection in the doubly-infected patient. Fri, 01 Jan 1999 00:00:00 GMT http://hdl.handle.net/2027.42/83672 1999-01-01T00:00:00Z http://hdl.handle.net/2027.42/83541 Revisiting Early Models of the host-pathogen interactions in HIV infection Covert, D.; Kirschner, Denise E. The interactions between infectious pathogens and the immune system have been mathematically modeled for numerous diseases. Human immunodeficiency virus (HIV), the agent that causes AIDS, has been modeled most extensively. In 1986, three years after HIV was isolated, investigators produced the first mathematical description of its pathogenesis. Since that time modelers have steadily developed more sophisticated systems that have brought the field of mathematical modeling to the consciousness of virologists and immunologists. In this paper we review five of the first attempts of modeling HIV and the immune system. We consider these models in their own right as predictors for CD4+ T-cell depletion and viral growth, as records of the immunovirological understanding of the day, and as forerunners of the current generation of models. Sat, 01 Jan 2000 00:00:00 GMT http://hdl.handle.net/2027.42/83541 2000-01-01T00:00:00Z