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Peripheral lymph nodes (PLNs) perform three central functions as a structural interface between the innate and adaptive immune systems: first, sentinel PLNs retain microbial­‐derived antigen (Ag) from the periphery arriving via afferent lymphatic vessels, therefore preventing the further spread into adjacent tissue. Second, macrophages and dendritic cells (DCs), which phagocytose microbial­‐derived Ag from peripheral sites, present Ag to passing lymphocytes within sentinel PLNs. During inflammation, PLNs typically undergo substantial morphological changes in size, blood and lymph vascularization, cell
number and subset composition, and cytokine levels. As a onsequence,
the numbers of blood and lymphatic endothelial cells, as well as stromal cells of the T cell zone and of B cell follicles increase to accommodate the rising influx of lymphocytes and influence the outcome of immune responses. Third, the lymphoid microenvironment and the T cell – DC interactions regulate the activation or tolerance induction of Ag-specific lymphocytes, as well as the further survival and
differentiation of These cells. Here, we propose to use novel stromal mutant mouse models, dynamic in vivo imaging of cellular interactions by twophoton microscopy (2PM) and cutting­‐edge mesoscopic imaging methods (Optical projection tomography, OPT and selective plane illumination microscopy, SPIM) created during the first Sinergia funding
period (2009­‐2012) to address the role for stromal cells during adaptive
and innate immune responses. Importantly, we will apply a comprehensive systems biology approach for mathematical modelling of high-resolution imaging data and functional analysis of PLN structure and its immunological relevance.