title: Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes.
abstract: BACKGROUND
  Lymph nodes (LNs) are positioned strategically throughout the body as critical mediators of lymph filtration and immune response. Lymph carries cytokines, antigens, and cells to the downstream LNs, and their effective delivery to the correct location within the LN directly impacts the quality and quantity of immune response. Despite the importance of this system, the flow patterns in LN have never been quantified, in part because experimental characterization is so difficult.
  
  
  RESULTS
  To achieve a more quantitative knowledge of LN flow, a computational flow model has been developed based on the mouse popliteal LN, allowing for a parameter sensitivity analysis to identify the important system characteristics. This model suggests that about 90% of the lymph takes a peripheral path via the subcapsular and medullary sinuses, while fluid perfusing deeper into the paracortex is sequestered by parenchymal blood vessels. Fluid absorption by these blood vessels under baseline conditions was driven mainly by oncotic pressure differences between lymph and blood, although the magnitude of fluid transfer is highly dependent on blood vessel surface area. We also predict that the hydraulic conductivity of the medulla, a parameter that has never been experimentally measured, should be at least three orders of magnitude larger than that of the paracortex to ensure physiologic pressures across the node.
  
  
  CONCLUSIONS
  These results suggest that structural changes in the LN microenvironment, as well as changes in inflow/outflow conditions, dramatically alter the distribution of lymph, cytokines, antigens, and cells within the LN, with great potential for modulating immune response.
authors.affiliation: 1 Department of Bioengineering, Imperial College , London, United Kingdom .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jafarnejad
authors.affiliation: 2 Emory Vaccine Center, Emory University , Atlanta, Georgia .
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Woodruff
authors.affiliation: 3 Department of Medical Physiology, Texas A&M Health Science Center , Temple, Texas.
authors.forename: David C
authors.initials: DC
authors.lastname: Zawieja
authors.affiliation: 4 Program in Cellular and Molecular Medicine, Boston Childrens Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.affiliation: 1 Department of Bioengineering, Imperial College , London, United Kingdom .
authors.forename: J E
authors.initials: JE
authors.lastname: Moore
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D008196:Lymph / Q000502:physiology*; D008198:Lymph Nodes / Q000098:blood supply / Q000502:physiology*; D051379:Mice; D008954:Models, Biological