Understanding the complexity of the immune system

Jeudi 25 Juin 2015 à 14h, Petit Amphi de Mathématiques, UFR Mathématique et Informatique, 7 rue Descartes, 67000 Strasbourg

Véronique Thomas-Vaslin
CNRS Researcher at I3 Lab and UPMC
Understanding the complexity of the immune system

The conference

Concepts used for the control of auto-organized systems and networks, were in fact established and selected during the evolution of living cells and organisms, allowing for molecular intercations, cell communications and signalling. Such concepts are also used to model the complexity of immune system, a microscopic cognitive and adaptive system that interacts with the microscopic environment as an ecosystem. From a engineering and modelling perspective the immune system designs a set of rules, processes and interactions linking entities as a dynamics system. Stochastic somatic diversity first generates a set of unique immuno-receptors on each lymphocyte, then learning through selective processes, related to avidity for antigens and signalling on each lymphocyte, allows building up a dynamic repertoire of lymphocytes with diverse immuno-receptors interacting in a multi-scale network. Upon activation this network insures the integrity and identity of the organism by the “immunoception” of any kind of antigens. This recapitulates an accelerated evolutionary selection process, in a single organism, related to its genetic origins, selective pressure of environment and historicity to adapt lymphocyte response to the context. The apparent resilience to perturbations is related to control feedback loops regulating linked entities but the systems also appears chaotic and fractal-like. While progressive organisation is required to set up the system, perturbations and aging contribute to the deterioration of the dissipative system, disorganisation, rupture of regulations and feedback, leading to pathologies like autoimmune and inflammatory diseases, with high prevalence in industrial societies. Modelling the immune system dynamics with black boxes and transition diagrams describing its heterogeneity and multi-scale dynamics can do improving our understanding of the complexity of the immune system. This modelling as populations or agents allows quantifying the dynamics of lymphocytes (proliferation, differentiation, selection, death, life span…), up to the migration of lymphocytes, positive and negative interactions with other cells or molecules to perform and regulate immune responses. This allows modelling the physiological behaviour and responses to perturbations or to treatments to better understand the immune system. Conversely, artificial immune systems a growing field from 1984 to 2008, are inspired from natural immune system properties to design decision and intrusion detection systems. Properties of the complex immune system could thus be used to design engineered systems.

Biography

Véronique THOMAS-VASLIN, has a PhD in Immunology from UPMC and is researcher in CNRS in Paris. Since 2008 she developed systems immunology approaches to have a global understanding of the immune system as a complex system and she has created the « Integrative Immunology: Differentiation, Diversity, Dynamics » team in the Immunology, Immunopathology, Immunotherapy UPMC INSERM UMRS959 CNRS FRE3632 Unit, Labex TransImmunom. Starting from experimental observations, she modelled T lymphocyte population dynamics in physiology and under perturbations by mathematical and computational approaches. As a member of Réseau National des Systèmes Complexes she created the ImmunoComplexiT network in 2011 and is involved in the direction committee of Institut des Systèmes Complexes - Paris Ile-de-France.

References

• CSRegistry Roadmap for complexity of the immune system
• Lavelle, C., H. Berry, G. Beslon, F. Ginelli, J. Giavitto, Z. Kapoula, A. Le Bivic, N. Peyrieras, O. Radulescu, A. Six, V. Thomas-Vaslin and P. Bourgine (2008). "From molecules to organisms: towards multiscale integrated models of biological systems." Theoretical Biology Insights 1: 13-22.
• Thomas-Vaslin, V., H. K. Altes, R. J. de Boer and D. Klatzmann (2008). "Comprehensive assessment and mathematical modeling of T cell population dynamics and homeostasis." J Immunol 180(4): 2240-2250.
• McEwan, C., H. Bersini, D. Klatzmann, V. Thomas-Vaslin and A. Six (2011). A computational technique to scale mathematical models towards complex heterogeneous systems, Luniver press. ISBN.
• Bersini, H., D. Klatzmann, A. Six and V. Thomas-Vaslin (2012). "State-transition diagrams for biologists." PLoS One 7(7): e41165.
• Thomas-Vaslin, V., A. Six, H. P. Pham, C. Dansokho, W. Chaara, B. Gouritin, B. Bellier and D. Klatzmann (2012). Immunodepression & Immunosuppression during aging. Immunosuppression. M. B. Portela. Brazil, InTech open acces publisher: 125-146.
• Thomas-Vaslin, V., A. Six, B. Bellier and D. Klatzmann (2013). Lymphocyte Dynamics and Repertoires, Biological Methods. Encyclopedia of Systems Biology. W. Dubitzky, O. Wolkenhauer, K.-H. Cho and H. Yokota, Springer New York: 1145-1149.
• Thomas-Vaslin, V., A. Six, B. Bellier and D. Klatzmann (2013). Lymphocytes dynamics and repertoires, modeling. Encyclopedia of Systems Biology. W. O. Dubitzky W, Springer, Heidelberg New York: 1149-1152.
• Thomas-Vaslin, V., A. Six, J. G. Ganascia and H. Bersini (2013). "Dynamical and mechanistic reconstructive approaches of T lymphocyte dynamics:Using visual modelling languages to bridge the gap between immunologists, theoreticians and programmers." Frontiers in Immunology 4: 300
• Abi Haidar, A., A. Six, J.-G. Ganascia and V. Thomas-Vaslin (2013). The Artificial Immune Systems Domain: Identifying Progress and Main Contributors Using Publication and Co-Authorship Analyses. Advances in Artificial Life, ECAL. 12: 1206–1217
• Thomas-Vaslin, V. (2014). "A complex immunological idiotypic network for maintenance of tolerance." Front Immunol 5: 369.
• Thomas-Vaslin, V. (2014). Evaluation de la résilience et des perturbations des systèmes complexes. La lettre de l’inSHS du CNRS. Paris, CNRS.
• Thomas-Vaslin, V. (à paraître, 2015). Complexité multi-échelle du système immunitaire: Evolution, du chaos aux fractales. Le vivant critique et chaotique. Editions Matériologiques. Paris.