Using math to better understand the immune defence
Mathematical models allow the complex balance of the immune system to be understood
Due to their highly effective suppression mechanism, regulatory T-cells are important for the regulation of the immune system. For their effect, exactly the right number of cells must be present in exactly the right place in the body. Scientists of the Helmholtz Centre for Infection Research (HZI) in Braunschweig were the first to develop a mathematical model that describes the homeostasis of these so-called Tregs in different immune organs. The results are published in the "European Journal of Immunology".
In a healthy organism, Tregs prevent autoimmune reactions resulting from the immune system erroneously recognising inherent structures of the body as foreign and attacking them. "You could call the regulatory T-cells the peace-keeping soldiers of the immune system," says Prof Jochen Hühn, head of the "Experimental Immunology" department at the HZI. But the old adage of "the more, the better" does not hold true in this case: If too many Tregs are present, they suppress the necessary and desired immune response to pathogens or tumours. The proper balance is therefore crucial for proper function of the immune system.
"To find out how the balance is maintained, we need to know the number of Tregs in various organs and have to understand how this number is controlled," says Hühn. Based on their experimental data, Hühn joined forces with Prof Michael Meyer-Hermann, head of the "Systems Immunology" department at the HZI, to develop a mathematical model that describes these complex processes and allows initial quantitative information concerning the generation of Tregs to be derived.
"We are attempting to use mathematical models to describe the influence of various factors on the entire immune system," says Meyer-Hermann. "In this case, we needed to produce a model that takes into account the situation in various organs at the same time." The multi-organ model produced by the scientists helps them make predictions about which components are important for the regulation of Tregs in the body.
"If we know these components, then we automatically have new starting points in the search for new therapeutic options," says Meyer-Hermann. Mainly, the mathematical model allows the researchers to design their experiments more specifically. "If we know the predictions, then we simply know better where to start with our search," says Hühn.
In the next step, experiments are needed to find out which part of the regulation does not work in ill people the way it works in healthy individuals. In the long term, this might lead to new therapeutic approaches. "This would then be owed to a large part to the close cooperation of mathematicians and immunologists," says Hühn. The cooperation will be intensified even more in the near future at the newly established Braunschweig Centre for Systems Biology (BRICS).
P. Milanez-Almeida, M. Meyer-Hermann, A. Toker, S. Khailaie, J. Huehn
Foxp3+ regulatory T-cell homeostasis quantitatively differs in murine peripheral lymph nodes and spleen.
European Journal of Immunology, 2014, DOI: 10.1002/eji.201444480
The "Experimental Immunology" department at the HZI investigates the origin of immune cells and the molecular and cellular mechanisms that maintain the balance of the immune system. A special focus of the scientists is on the role of the so-called regulatory T-cells.
The "Systems Immunology" department of the HZI investigates the mathematical modelling of immunological processes. The department is associated with the Braunschweig Integrated Centre for Systems Biology (BRICS), a new research centre for Systems Biology that has been established jointly by the HZI and the Technical University Braunschweig.
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- 1456 Durch Mathematik die Immunabwehr besser verstehen (pdf, 541 kB)