Regulation of organism's antiviral immune response: mathematical model, qualitative analysis, results

P. V. Trusov ; N. V. Zaitseva ; V. M. Chigvintsev ; D. V. Lanin

Matematičeskaâ biologiâ i bioinformatika, Tome 18 (2023) no. 3, pp. t17-t37

Résumé

To know the processes occurring in the neuroendocrine and immune system, the complex and branching regulation mechanisms should be taken into account. Most of the studies in this area are dedicated to the biological and mathematical description of individual parts of the regulatory mechanisms, and it greatly facilitates the understanding of the phenomena being studied. But there is a lack of comprehensive description of the processes and internal communications. In the present article, a mathematical model for describing the antiviral immune response is considered taking into account the interacting regulatory influences of the immune and neuroendocrine systems. To describe the innate immunity, the proposed model uses parameters reflecting quantitative measures of the interferon concentration (the inductor of resistance to the infection of target organ cells) and NK-cells (responsible for removing of the infected cells). The simulation of acquired immunity is performed using parameters characterizing the concentration of virus-specific cytotoxic T cells and antibody-forming B lymphocytes. The regulatory mechanisms considered in the model cover the influence of the hypothalamic-pituitary-adrenal axis and the populations of the T-helper cells. The model is developed within the framework of the concept of a multi-level model of the human body, taking into account the interactions between systems and the functional state of the organs included in the review. The model also takes into account the spatial organization of immune and infectious processes in various organs and tissues, for which the delay time of interaction of the components is introduced. The model includes a system of 18 ordinary differential equations with a delayed argument, the parameters of which characterize the rates of various processes that affect the dynamics of infection. The parameters are identified according to published experimental data describing the process of infection of the body with a virus. The dynamics of the immune and neuroendocrine systems under viral infection was calculated, taking into account the disturbance of the synthetic function of the bone marrow. The study provides a qualitative picture of the biological factors that can explain the kinetics of the development of a viral infection.

Bibliographie

[1] C. J. Heijnen, “Receptor regulation in neuroendocrine-immune communication: current knowledge and future perspectives”, Brain, behavior, and immunity, 21 (2007), 1–8 | DOI | DOI

[2] T. W. Pace, L. T. Negi, D. D. Adame, S. P. Cole, T. I. Sivilli, T. D. Brown, M. J. Issa, C. L. Raison, “Effect of compassion meditation on neuroendocrine, innate immune and behavioral responses to psychosocial stress”, Psychoneuroendocrinology, 34 (2009), 87–98 | DOI | DOI

[3] N. T. Ashley, G. E. Demas, “Neuroendocrine-immune circuits, phenotypes, and interactions”, Hormones and Behavior, 87 (2017), 25–34 | DOI | DOI

[4] E. C. Suarez, J. S. Sundy, A. Erkanli, “Depressogenic vulnerability and gender-specific patterns of neuro-immune dysregulation: What the ratio of cortisol to C-reactive protein can tell us about loss of normal regulatory control”, Brain, Behavior, and Immunity, 44 (2015), 137–147 | DOI | DOI

[5] D. V. Lanin, N. V. Zaitseva, O. V. Dolgikh, Successes of modern biology, 2 (2011), 122–134 (in Russ.)

[6] M. Bellavance, S. Rivest, “The neuroendocrine control of the innate immune system in health and brain diseases”, Immunological Reviews, 248 (2012), 36–55 | DOI | DOI

[7] C. R. Chapman, R. P. Tuckett, C. W. Song, “Pain and Stress in a Systems Perspective: Reciprocal Neural, Endocrine, and Immune Interactions”, Journal of Pain, 9 (2008), 122–145 | DOI | DOI

[8] S. Miyake, “Mind over cytokines: Crosstalk and regulation between the neuroendocrine and immune systems”, Clinical and Experimental Neuroimmunology, 3:1 (2012), 1–15 | DOI | DOI

[9] A. B. Poletaev, S. G. Morozov, I. E. Kovalev, Regulatory metasystem (immunoneurococcal regulation of homeostasis, M., 2002, 166 pp. (in Russ.)

[10] World health statistics 2016: monitoring health for the SDGs, sustainable development goals, World Health Organization, 2016, 121 pp.

[11] L. A. Stepanenko, S. V. Il'ina, E. D. Savilov, Bulletin of the East-Siberian Scientific Center of the Siberian Branch of the Russian Academy of Medical Sciences, S3 (2007), 66–68 (in Russ.)

[12] Documents, , Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 2018 (accessed 20.11.2018) http://www.rospotrebnadzor.ru/en/documents/

[13] E. D. Savilov, M. V. Mal'tsev, Journal of Microbiology, Epidemiology and Immunobiology, 1 (2007), 70–71 (in Russ.)

[14] E. E. Voronin, I. B. Latysheva, “VICh-infektsiia v Rossiiskoi Federatsii”, Ural Medical Journal, 142 (2016), 6–8 (in Russ.)

[15] L. A. Stepanenko, M. F. Savchenkov, S. V. Il'ina, E. V. Anganova, E. D. Savilov, Hygiene and Sanitation, 95 (2016), 1129–1133 (in Russ.) | DOI | DOI

[16] E. D. Savilov, E. V. Anganova, S. V. Il'ina, L. A. Stepanenko, Hygiene and Sanitation, 95 (2016), 507–512 (in Russ.) | DOI | DOI

[17] E. D. Savilov, S. V. Il'ina, Epidemiology and vaccine prevention, 62 (2012), 58–63 (in Russ.)

[18] N. V. Zaitseva, D. V. Lanin, V. A. Chereshnev, Immune and neuroendocrine regulation under the influence of chemical factors of various origins, Perm', 2016, 236 pp. (in Russ.)

[19] D. V. Lanin, Health Risk Analysis, v. 1, 2013, 73–81 (in Russ.) | DOI | DOI

[20] N. V. Zaitseva, D. A. Kiryanov, D. V. Lanin, V. M. Chigvintsev, “A mathematical model of the immune and neuroendocrine systems mutual regulation under the technogenic chemical factors impact”, Computational and Mathematical Methods in Medicine, 2014 (2014) | DOI | MR | DOI | MR

[21] N. V. Zaitseva, P. V. Trusov, P. Z. Shur, D. A. Kir'ianov, V. M. Chigvintsev, M. Iu. Tsinker, Health Risk Analysis, v. 1, 2013, 3–11 (in Russ.) | DOI | MR | Zbl | DOI | MR | Zbl

[22] N. V. Zaitseva, P. Z. Shur, I. V. Mai, D. A. Kir'ianov, Public health and habitat, 10 (2011), 6–9 (in Russ.)

[23] D. V. Lanin, T. M. Lebedeva, Hygiene and Sanitation, 95 (2016), 94–96 (in Russ.) | DOI | DOI

[24] P. Zabel, H. J. Horst, C. Kreiker, M. Schlaak, “Circadian rhythm of interleukin-1 production of monocytes and the influence of endogenous and exogenous glucocorticoids in man”, Klinische Wochenschrift, 68 (1990), 1217–1221 | DOI | DOI

[25] N. Bairagi, S. Chatterjee, J. Chattopadhyay, “Variability in the secretion of corticotropin releasing hormone, adrenocorticotropic hormone and cortisol and understandability of the hypothalamic-pituitary-adrenal axis dynamics a mathematical study based on clinical evidence”, Mathematical Medicine and Biology, 25 (2008), 37–63 | DOI | Zbl | DOI | Zbl

[26] Y. Kerdiles, S. Ugolini, E. Vivier, “T cell regulation of natural killer cells”, The Journal of Experimental Medicine, 210 (2013), 1065–1068 | DOI | DOI

[27] M. E. Andrew, A. M. Churilla, T. R. Malek, V. L. Braciale, T. J. Braciale, “Activation of virus specific CTL clones: antigen-dependent regulation of interleukin 2 receptor expression”, J. Immunol., 134:2 (1985), 920–925 | DOI | DOI

[28] A. Muraguchi, J. H. Kehrl, D. L. Longo, D. J. Volkman, K. A. Smith, A. S. Fauci, “Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function”, The Journal of Experimental Medicine, 161 (1985), 181–197 | DOI | DOI

[29] E. Haus, M. H. Smolensky, “Biologic rhythms in the immune system”, Chronobiology International, 16 (1999), 581–622 | DOI | DOI

[30] G. E. Demas, S. A. Adamo, S. S. French, “Neuroendocrine-immune crosstalk in vertebrates and invertebrates: Implications for host defence”, Functional Ecology, 25 (2011), 29–39 | DOI | DOI

[31] G. I. Marchuk, R. V. Petrov, A. A. Romanyukha, G. A. Bocharov, “Mathematical model of antiviral immune response. I. Data analysis, generalized picture construction and parameters evaluation for hepatitis B”, Journal of Theoretical Biology, 151 (1991), 1–40 | DOI | DOI

[32] I. Julkunen, K. Melen, M. Nyqvist, J. Pirhonen, T. Sareneva, S. Matikainen, “Inflammatory responses in influenza A virus infection”, Vaccine, 19 (2000), S32–S37 | DOI | DOI

[33] G. A. Bocharov, A. A. Romanyukha, “Mathematical model of antiviral immune response. III. Influenza A virus infection”, Journal of Theoretical Biology, 167:4 (1994), 323–360 | DOI | DOI

[34] K. P. Keenan, J. W. Combs, E. M. McDowell, “Regeneration of hamster tracheal epithelium after mechanical injury. III. Large and small lesions: Comparative stathmokinetic and single pulse and continuous thymidine labeling autoradiographic studies”, Virchows Archiv B Cell Pathology Including Molecular Pathology, 41:1 (1983), 231–252 | DOI | DOI

[35] Joklik W. K., Interferons, ed. B.N. Fields, Raven Press, New York, 1985, 281–307

[36] A. S. Perelson, R. M. Ribeiro, “Modeling the within-host dynamics of HIV infection”, BMC Biology, 11 (2013), 96 | DOI | DOI

[37] A. M. Smith, A. S. Perelson, “Influenza A virus infection kinetics: Quantitative data and models”, WIREs: Systems Biology and Medicine, 3:4 (2011), 429–445 | DOI | MR | DOI | MR

[38] F. Vinther, M. Andersen, J. T. Ottesen, “The minimal model of the hypothalamic pituitary-adrenal axis”, Journal of Mathematical Biology, 63:4 (2011), 663–690 | DOI | MR | Zbl | DOI | MR | Zbl

[39] V. M. Zhdanov, A. G. Bukrinskaia, Reproduction of myxoviruses (influenza viruses and related viruses), M., 1969, 280 pp. (in Russ.)

[40] T. Ronni, T. Sareneva, J. Pirhonen, I. Julkunen, “Activation of IFN-alpha, IFN-gamma, MxA, and IFN regulatory factor 1 genes in influenza A virus-infected human peripheral blood mononuclear cells”, Journal of Immunology, 154:6 (1995), 2764–2774 | DOI | DOI

[41] T. Sareneva, S. Matikainen, M. Kurimoto, I. Julkunen, “Influenza A virus-induced IFN alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells”, Journal of Immunology, 160:12 (1998), 6032–6038 | DOI | DOI

[42] G. I. Marchuk, E. P. Berbentsova, Acute pneumonia. Immunology, assessment of severity, clinic, treatment, M., 1989, 304 pp. (in Russ.)

[43] F. G. Hayden, R. Fritz, M. C. Lobo, W. Alvord, W. Strober, S. E. Straus, “Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense”, Journal of Clinical Investigation, 101:3 (1998), 643–649 | DOI | DOI

[44] C. Wohlfartt, “Neutralization of Adenoviruses: Kinetics, Stoichiometry, and Mechanisms”, J. Immunol., 62:7 (1988), 2321–2328

[45] Y. Bergeron, N. Ouellet, A. Deslauriers, M. Simard, M. Olivier, M. Bergeron, “Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice”, Infect. Immun., 66:3 (1998), 912–922 | DOI | DOI

[46] C. Gloff, R. Wills, “Pharmacokinetics and Metabolism of Therapeutic Cytokines”, Protein Pharmacokinetics and Metabolism, eds. B. Ferraiolo, M. Mohler, C. Gloff, Plenum Press, New York, 1992, 127–150 | DOI | DOI

[47] A. Tulp, D. Verwoerd, B. Dobberstein, H. L. Ploegh, J. Pieters, “Isolation and characterization of the intracellular MHC class II compartment”, Nature, 369:6476 (1994), 120–126 | DOI | DOI

[48] S. I. Tamura, T. Iwasaki, A. H. Thompson, H. Asanuma, Z. Chen, Y. Suzuki, C. Aizawa, T. Kurata, “Antibody-forming cells in the nasal-associated lymphoid tissue during primary influenza virus infection”, Journal of General Virology, 79:2 (1998), 291–299 | DOI | DOI

[49] P. Felig, L. Frohman, Endocrinology and metabolism, McGraw-Hill, New York, 2001, 1562 pp.

[50] B. J. Carroll, F. Cassidy, D. Naftolowitz, N. E. Tatham, W. H. Wilson, A. Iranmanesh, P. Y. Liu, J. D. Veldhuis, “Pathophysiology of hypercortisolism in depression”, Acta Psychiatrica Scandinavica, 115 (2007), 90–103 | DOI | DOI

[51] R. A. Yetter, S. Lehrer, R. Ramphal, P. A. Small Jr., “Outcome of influenza infection: effect of site of initial infection and heterotypic immunity”, Infect. Immun., 29 (1980), 654–662 | DOI | DOI

[52] B. Asquith, C. R. Bangham, “An introduction to lymphocyte and viral dynamics: the power and limitations of mathematical analysis”, Proc. Biol. Sci., 270 (2003), 1651–1657 | DOI | DOI