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Our research plan includes three complementary subprojects, which are carried-out in a highly synergistic manner by the partners Dr. Stein (UBERN), Prof. Ludewig (KSSG) and Dr. Sharpe (CRG), respectively. The three subprojects address the following aspects of image-­based modeling of adaptive immune responses: first, we will integrate innovative imaging developments into the OPTiSPIM hybrid setup – in particular aiming at high-­‐resolution mesoscopic imaging –
and transfer SPIM technology from CRG to UBERN. Second, we will analyze the impact of stromal cell-­expressed signaling molecules, including the lymphotoxin β receptor, MyD88 and Interferon A receptor, on the early phase of antiviral immune responses, as well as the functional role of lymphatic vessel restructuring at later phases. In parallel, we will exploit mesoscopic 3D image information to generate high-­resolution mathematical models of PLNs during steady state and inflammation. Finally, various models will be integrated for multiscale simulation, which will be complemented by tissue-­level mathematical modeling of inflammation-­induced changes
of the PLN architecture. From the sum of our data, we anticipate a synergistic increase in our understanding of antiviral immune responses at an unprecedented level.