Scaling aspects of lymphocyte trafficking

Abstract

We consider the long lived pool of B and T cells that recirculate through blood, tissues and the lymphatic system of an animal with body mass M. We derive scaling rules (allometric relations) for:(1) the rate of production of mature lymphocytes; (2) the accumulation of lymphocytes in the tissues; (3) the flux of lymphocytes through the lymphatic system; (4) the number of lymph nodes, (5) the number of lymphocytes per clone within a lymph node, and (6) the total number of lymphocytes within a lymph node. Mass-dependent aspects of immune learning and of the immunological self are shown to be not very significant. Our treatment is somewhat heuristic and aims at a combination of immunological data with recent progress in biological scaling.

Spatial modeling of HIV cryptic viremia and 2-LTR formation during raltegravir intensification

“…If naive lymphocytes do not encounter antigens, they eventually leave the paracortex by the cortical sinus and the lymph node through efferent lymphatics. The total recirculation time is estimated to be between 52 and 69 hours on average [32]…”

Regulatory T-Cell Therapy in Transplantation: Moving to the Clinic

“…Scaling for immune cell therapy may be less complicated and unpredictable than that for small molecule drugs because pharmacokinetic and pharmacodynamic properties of immune cells (i.e., rules for cell trafficking, turnover, and dose response) are relatively insensitive to the differences in body mass and metabolic rate of different species (Wiegel and Perelson 2004;Perelson and Wiegel 2009). For example, clinical data obtained from hematopoietic stem cell transplant shows that the minimal effective dose for neutrophil and platelet reconstitution in humans is consistent with that predicted by allometric scaling of data from animal models.…”

Reaction-Diffusion Modelling of Interferon Distribution in Secondary Lymphoid Organs

“…The focus should be made on the development of hybrid multiphysics models which integrate the spatial migration of cells and soluble substances in the lymphoid system with the real 3D geometry of immune responses microanatomy in SLO, calibrated using high-resolution fluorescence microscopy data. Although, there is a growing interest to explore the spatial complexities of the immune processes using mathematical models [2,3,4,14,18,25], the real 3D geometry of the SLO remains to be properly considered. Further studies of the similar to the presented here and recent imaging technology-driven computational developments [15] should provide a proper basis for a transition in the current modelling paradigm of mathematical immunology from a phenomenological, spatially degenerate approach to a multiphysics-based high-resolution description of immune responses in physiological environment of the organized lymphoid tissues [30].…”