Understanding and Modelling the Complexity of the Immune System: Systems Biology for Integration and Dynamical Reconstruction of Lymphocyte Multi-Scale Dynamics
Résumé
Understanding and modelling the complexity of the immune system is a challenge that is shared by the ImmunoComplexiT 1 thematic network from the RNSC The immune system is a complex biological, adaptive, highly diversified, self-organized and degenerative cognitive network of entities, allowing for a robust and resilient system with emergent properties such as anamnestic responses and regulation. The adaptive immune system has evolved into a complex system of billions of highly diversified lymphocytes all interacting as a connective dynamic, multi-scale organised and distributed system, in order to collectively insure body and species preservation. The immune system is characterized by complexity at different levels: network organisation through fluid cell populations with inter-and intra-cell signalling, lymphocyte receptor diversity, cell clonotype selection and competition at cell level, migration and interaction inside the immunological tissues and fluid dissemination through the organism, homeostatic regulation while rapid adaptation to a changing environment. Lymphocytes are the key actors of the immune system of vertebrates, in the middle of a multi-scale biological organization "from molecule to organism", and at the confluence with other different biological systems and the environment. Produced in central lymphoid organs by complex steps of differentiation, lymphocytes are then distributed in circulation and peripheral lymphoid organs to insure the integrity of the organism, composed of eukaryote and prokaryote cells and antigens. Each lymphocyte has a unique immuno-receptor type, generated by somatic gene rearrangement. The lymphocyte repertoire is able to recognize a potential repertoire of 10 19 antigens. Lymphocyte repertoire selection is related to complex lymphocyte/Ag interaction to purge >95% of the cells that have not enough or to much affinity to antigens. It selects effector cells and regulatory cells involved in regulation of the immune response, insuring a dominant tolerance regulation process. There is a physiological basal production and activation of lymphocytes. The high turnover of lymphocytes and their immediate precursors is insured by daily renewal, differentiation and selection processes, proliferation and cell death, both in the central and peripheral lymphoid tissues. The cognition of antigens in individuals induces selection of lymphocyte repertoire via the immune-receptor. Thus, complex multilevel dynamic interactions at different time and space scales lead to a decentralised autonomous robust and resilient system. In young individuals this system is able to rapidly 1 http://www.immunocomplexit.net/
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