Lymph node transport and its potential roles in immunology

Image

James Moore

Mardi 9 avril à 11h00, salle des séminaires IRPHE

Abstract : Lymphatic vessels serve to return interstitial fluid centrally to the blood system, a process that relies on their biomechanical properties and active pumping. Prior to its return to blood, lymph must be “filtered” for antigens as an important component of the immune system.  Lymph Nodes serve as information collection/distribution hubs for innate and adaptive immunity, actively delivering antigen information to the appropriate cell types.  The size of a human lymph node (order of cm) is such that diffusive and flow-mediated processes are required to distribute information effectively.  Specialized blood vessels also run throughout lymph nodes, providing transmural transport of millions of lymphocytes. Small (<70kDa) antigens arriving in solution via afferent lymph are transported via conduits formed of collagen fibers, while larger antigens are distributed through the parenchyma.  Antigen presenting cells follow chemokine gradients to find their way to the appropriate nodal compartments.  Both antigens and chemokines can be transported by diffusion or advection.  Using a combination of multiscale experimental and mathematical approaches, we have investigated the transport of solutes and cells from interstitial spaces into and through lymph nodes.  Our results indicate that transport in conduits is nearly entirely diffusive, with collagen fibers providing anisotropic diffusivity.  This delivers small amounts of solutes efficiently to targeted locations.  Lymph flow is important for formation of chemokine gradients in the parenchyma, which behaves more as a porous medium. These vastly different transport regimes can be targeted for optimal immune response to vaccines, and are likely involved in progression of cancer metastases.

James E Moore / Department of Bioengineering, Imperial College London, UK