Mathematical model of antiviral immune response. I. Data analysis, generalized picture construction and parameters evaluation for hepatitis B.

The present approach to the mathematical modelling of infectious diseases is based upon the idea that specific immune mechanisms play a leading role in development, course, and outcome of infectious disease. The model describing the reaction of the immune system to infectious agent invasion is constructed on the bases of Burnet's clonal selection theory and the co-recognition principle. The mathematical model of antiviral immune response is formulated by a system of ten non-linear delay-differential equations. The delayed argument terms in the right-hand part are used for the description of lymphocyte division, multiplication and differentiation processes into effector cells. The analysis of clinical and experimental data allows one to construct the generalized picture of the acute form of viral hepatitis B. The concept of the generalized picture includes a quantitative description of dynamics of the principal immunological, virological and clinical characteristics of the disease. Data of immunological experiments in vitro and experiments on animals are used to obtain estimates of permissible values of model parameters. This analysis forms the bases for the solution of the parameter identification problem for the mathematical model of antiviral immune response which will be the topic of the following paper (Marchuk et al., 1991, J. theor. Biol. 15).

[1]  J. Hall Studies on the adjuvant action of beryllium. I. Effects on individual lymph nodes. , 1984, Immunology.

[2]  A S Perelson,et al.  Mechanism of cell-mediated cytotoxicity at the single cell level. VIII. Kinetics of lysis of target cells bound by more than one cytotoxic T lymphocyte. , 1979, Journal of immunology.

[3]  I. Mushahwar,et al.  Viral hepatitis, type B. Studies on natural history and prevention re-examined. , 1979, The New England journal of medicine.

[4]  G. Marchuk,et al.  Mathematical model of antiviral immune response. II. Parameters identification for acute viral hepatitis B. , 1991, Journal of theoretical biology.

[5]  G. Colucci,et al.  In situ characterization by monoclonal antibodies of the mononuclear cell infiltrate in chronic active hepatitis. , 1983, Gastroenterology.

[6]  M. Omata,et al.  Appearance of viral RNA transcripts in the early stage of duck hepatitis B virus infection. , 1986, Virology.

[7]  R. Zinkernagel,et al.  On the role of viruses in the evolution of immune responses. , 1985, British medical bulletin.

[8]  K. Isselbacher,et al.  Hepatitis B viral antigenic structure: signature analysis by monoclonal radioimmunoassays. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. J. Kozak,et al.  A dynamic model for in vivo virus replication. , 1981, Journal of theoretical biology.

[10]  F. Burnet The clonal selection theory of acquired immunity , 1959 .

[11]  Chesnut Rw,et al.  Antigen presenting cells and mechanisms of antigen presentation. , 1985 .

[12]  F. Deinhardt Serum markers of hepatitis viruses in natural disease and after vaccination. , 1982, Progress in liver diseases.

[13]  S. Sylvan,et al.  Detection of cellular and humoral immunity to hepatitis B surface antigen (HBsAg) in asymptomatic HBsAg carriers. , 1985, Clinical and experimental immunology.

[14]  R. Purcell,et al.  Cell-mediated immunity to hepatitis B surface antigen in man. , 1984, Clinical and experimental immunology.

[15]  A. Coutinho,et al.  Two major classes of mitogen-reactive B lymphocytes defined by life span. , 1986, Journal of immunology.

[16]  B. Morris,et al.  The lymph-borne response of foetal lamb lymph nodes to challenge with Brucella abortus in utero. , 1985, Australian Journal of Experimental Biology and Medical Science.

[17]  R. E. Cunningham,et al.  Regulation of interleukin 2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin or antigen. , 1984, Journal of immunology.

[18]  H. Thomas,et al.  Neutralization of Hepatitis B Virus Infectivity by a Murine Monoclonal Antibody: An Experimental Study in the Chimpanzee , 1985, Journal of medical virology.

[19]  J. Bard A quantitative model of liver regeneration in the rat. , 1978, Journal of theoretical biology.

[20]  W. Paul,et al.  Polyclonal stimulation of resting B lymphocytes by antigen-specific T lymphocytes , 1984, The Journal of experimental medicine.

[21]  E. Unanue,et al.  The handling of Listeria monocytogenes by macrophages: the search for an immunogenic molecule in antigen presentation. , 1984, Journal of immunology.

[22]  A. Coutinho,et al.  Activation and growth requirements for cytotoxic and noncytotoxic T lymphocytes. , 1984, Cellular immunology.

[23]  C. Howard,et al.  HBsAg: anti-HBs immune complexes. A method for separating the constituent components and assessment of the affinity of the antibody. , 1986, Journal of immunological methods.

[24]  P Hogeweg,et al.  Macrophage T lymphocyte interactions in the anti-tumor immune response: a mathematical model. , 1985, Journal of immunology.

[25]  I. Weissman,et al.  Localization of lymphocyte subpopulations in peripheral lymphoid organs: directed lymphocyte migration and segregation into specific microenvironments. , 1984, The American journal of anatomy.

[26]  R. Purcell,et al.  A final report on safety and immunogenicity of a bivalent aqueous subunit HBV vaccine , 1985, Journal of medical virology.

[27]  C. A. Macken,et al.  A multistage model for the action of cytotoxic T lymphocytes in multicellular conjugates. , 1984, Journal of immunology.

[28]  A. Perelson,et al.  Delivery of lethal hits by cytotoxic T lymphocytes in multicellular conjugates occurs sequentially but at random times. , 1982, Journal of immunology.

[29]  S. Vogel,et al.  Antagonistic effect of interferon-beta on the interferon-gamma-induced expression of Ia antigen in murine macrophages. , 1985, Journal of immunology.

[30]  A. Perelson Immune Network Theory , 1989, Immunological reviews.

[31]  J. Williams,et al.  T cell synergy in the primary MLR: proliferative kinetics, effector cell generation, and IL 2 production. , 1984, Journal of immunology.

[32]  G. Alexander,et al.  Relationship Between Expression of Hepatitis B Virus Antigens in Isolated Hepatocytes and Autologous Lymphocyte Cytotoxicity in Patients with Chronic Hepatitis B Virus Infection , 1984, Hepatology.

[33]  S. Kauffman,et al.  Adaptive Dynamic Networks as Models for the Immune System and Autocatalytic Sets , 1987, Annals of the New York Academy of Sciences.

[34]  D. Vergani,et al.  Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes. , 1982, Journal of immunology.

[35]  G. Milon,et al.  Numeration of DTH-mediating T lymphocytes in mice under optimal titration conditions. , 1984, Annales d'immunologie.

[36]  A. Guillouzo,et al.  Human hepatocyte cultures. , 1986, Progress in liver diseases.

[37]  A. Abbas,et al.  Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4- and interleukin 2-producing T cell clones on resting B lymphocytes , 1988, The Journal of experimental medicine.

[38]  C. Wohlfart,et al.  Neutralization of adenoviruses: kinetics, stoichiometry, and mechanisms , 1988, Journal of virology.

[39]  W. Bowers,et al.  Dendritic cells: historical perspective and role in oxidative mitogenesis. , 1984, Immunobiology.

[40]  J. Wands,et al.  Correlation of HBV DNA and monoclonal reactivity to HBsAg in serum of patients with HBV infection. , 1986, Journal of virological methods.

[41]  S. Gromkowski,et al.  The Mechanism of CTL‐Mediated Killing: Monoclonal Antibody Analysis of the Roles of Killer and Target‐Cell Membrane Proteins , 1983, Immunological reviews.

[42]  E. Unanue,et al.  Antigen processing and presentation by macrophages. , 1984, The American journal of anatomy.

[43]  G W Hoffmann,et al.  Qualitative dynamics of a network model of regulation of the immune system: a rationale for the IgM to IgG switch. , 1982, Journal of Theoretical Biology.

[44]  D. Milich Genetic and Molecular Basis for T‐ and B‐Cell Recognition of Hepatitis B Viral Antigens , 1987, Immunological reviews.

[45]  H. Ziegler,et al.  Modulation of macrophage Ia-expression by lipopolysaccharide. I. Induction of Ia expression in vivo. , 1984, Journal of immunology.

[46]  L. Ranek,et al.  Functioning liver mass in uncomplicated and fulminant acute hepatitis. , 1980, Scandinavian journal of gastroenterology.

[47]  T. Issekutz Characteristics of lymphoblasts appearing in efferent lymph in response to immunization with vaccinia virus. , 1985, Immunology.

[48]  A. Schimpl Lymphokines active in B cell proliferation and differentiation , 2004, Springer Seminars in Immunopathology.

[49]  G. I. Bell,et al.  Mathematical model of clonal selection and antibody production. III. The cellular basis of immunological paralysis. , 1971, Journal of theoretical biology.

[50]  R.R. Mohler,et al.  A systems approach to immunology , 1980, Proceedings of the IEEE.

[51]  T. Issekutz Kinetics of cytotoxic lymphocytes in efferent lymph from single lymph nodes following immunization with vaccinia virus. , 1984, Clinical and experimental immunology.

[52]  I. Weissman Lymphocyte homing receptors and the immune response in vivo , 1986, BioEssays : news and reviews in molecular, cellular and developmental biology.

[53]  E. Jones Hepatic Sinusoidal Cells: New Insights and Controversies , 2007, Hepatology.

[54]  J. Bard A quantitative theory of liver regeneration in the rat. II: matching an improved mitotic inhibitor model to the data. , 1979, Journal of theoretical biology.

[55]  M Kaufman,et al.  Model analysis of the bases of multistationarity in the humoral immune response. , 1987, Journal of theoretical biology.

[56]  P. Horan,et al.  Cell-mediated cytotoxicity. A highly sensitive and informative flow cytometric assay. , 1989, Journal of immunological methods.

[57]  A. Eddleston,et al.  The role of immunological mechanisms in chronic hepatitis. , 1976, Annals of clinical research.

[58]  A. Moretta Frequency and surface phenotype of human T lymphocytes producing interleukin 2. Analysis by limiting dilution and cell cloning , 1985, European journal of immunology.

[59]  G. I. Bell,et al.  Mathematical model of clonal selection and antibody production. , 1970, Journal of theoretical biology.

[60]  P Nieuwenhuis,et al.  Functional anatomy of germinal centers. , 1984, The American journal of anatomy.

[61]  G. Doria,et al.  Defective antigen presentation by macrophages from mice genetically selected for low antibody response , 1981, European journal of immunology.

[62]  H. Dosch,et al.  Differential regulation of activation, clonal expansion, and antibody secretion in human B cells. , 1985, Journal of immunology.

[63]  R. Zinkernagel,et al.  Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system , 1974, Nature.

[64]  Alessandro Bertuzzi,et al.  Maximum likelihood identification of an immune response model , 1979 .

[65]  F. Karush The Affinity of Antibody: Range, Variability, and the Role of Multivalence , 1978 .

[66]  S. Aspinall,et al.  Comparative expression of hepatitis B virus antigens in several cell model systems. , 1986, The Journal of general virology.

[67]  D. Mosier T cell activation of antigen-specific antibody responses by large B cells is MHC restricted. , 1986, Journal of immunology.