SYSTEM DYNAMICS ANALYSIS OF THE IMMUNOLOGICAL RESPONSE TO VIRAL INFECTION, WITH PARTICULAR REFERENCE TO THE PATHOGENESIS OF ACQUIRED IMMUNE DEFICIENCY SYNDROME

Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

SYSTEM DYNAMICS ANALYSIS OF THE IMMUNOLOGICAL RESPONSE TO VIRAL INFECTION, WITH PARTICULAR REFERENCE TO THE PATHOGENESIS OF ACQUIRED IMMUNE DEFICIENCY SYNDROME

Diss Abstr Int [B]; 51(2):654 1990. Unique Identifier : AIDSLINE ICDB/90668480
Whitaker RED; Boston Univ.

Abstract: The mechanisms essential to the pathogenesis of Human Immunodeficiency Virus (HIV) infection have been extremely difficult to determine to date. The magnitude and breadth of immunological abnormalities and the conundrum of a relatively low viral load in the presence of high titres of HIV-specific anti-viral antibodies have served to obscure these mechanisms. A thorough examination of the experimental literature provides an overview of the problem and helps to isolate candidate pathogenetic mechanisms. Two analytic models are then reported, of the response to normal viral and retroviral infection, respectively. These represent first steps in the development of systems dynamics models in theoretical immunovirology and are used to examine the network structure of the immune response, in order to determine the causes of the development of HIV-associated disease, and to provide a rationale for therapeutic interventions. On the basis of both literature review and the models, it is concluded that: autoimmunity by cytotoxic T cells and by antibody-dependent cell-mediated cytotoxicity is essential to cell death and disease development; the inhibition of precursor cell maturation is essential to the development and/or maintenance of both non-progression of disease and to the development of clinical symptomatology, in interaction with cell death; viral cytopathicity is not responsible for significant cell death; shed gp120 is essential to the development of both dis-regulated immunity and tolerance and determines the dynamics of cell death; and non-specific activation of the immune system determines, at least in part, the time of onset of clinical abnormalities. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD90-16765)

Keywords: Acquired Immunodeficiency Syndrome/COMPLICATIONS/*IMMUNOLOGY/ MICROBIOLOGY Antibody-Dependent Cell Cytotoxicity Autoimmunity Cytopathogenic Effect, Viral Human HIV Antibodies/IMMUNOLOGY HIV Envelope Protein gp120/IMMUNOLOGY HIV-1/*IMMUNOLOGY/PHYSIOLOGY T-Lymphocytes, Cytotoxic/IMMUNOLOGY THESIS
901230
M90C3722

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