Lymphatic System Transport and Vaccine Design: James Moore

Speaker: James Moore, Imperial College London, UK
An important criterion for vaccine success is the transport of information into lymph nodes, where immune cells exist in sufficient density to facilitate adaptive immunity. This is the responsibility of the prenodal lymphatic system, which consists of porous initial lymphatics and actively pumping collecting lymphatic vessels. Antigen information can remain suspended in lymph or be captured by antigen presenting cells. Once inside the node, fluid flow and solute transport are crucial for delivering the information to specific cell types. In vivo observations of these transport processes are challenged by the lack of appropriate tools for measuring lymphatic flows. We have initiated a series of experiments and numerical simulations to investigate the roles of fluid transport in the various processes that support adaptive immunity. We have constructed porous media mathematical models for the lymph compartment, coupled to models of viscous flow in lymph node blood vessels to simulate the effects of vaccination. We have also coupled these to advection-diffusion-reaction models that simulate the migratory stimulatory effects of chemokines on immune cells. Microfluidic chamber experiments with controllable advection and ability to visualise cell migration in real time supports these models. Vaccination has strong effects on rat mesenteric collecting lymphatic pumping dynamics and fluid shifts within lymph nodes. The transport of small antigens in solution occurs primarily by diffusion in small (1µm diameter) collagen-bundle conduit structures. These results provide insights on ways to modulate