Physiological factors leading to a successful vaccination: A computational approach

Authored by Dominic L Maderazo, Jennifer A Flegg, Melanie R Neeland, Veer Michael J de, Mark B Flegg

Date Published: 2018

DOI: 10.1016/j.jtbi.2018.06.008

Sponsors: No sponsors listed

Platforms: No platforms listed

Model Documentation: Other Narrative Mathematical description

Model Code URLs: Model code not found

Abstract

The immune system mounts a response to an infection by activating T cells. T cell activation occurs when dendritic cells, which have already interacted with the pathogen, scan a T cell that is cognate for (responsive to) the pathogen. This often occurs inside lymph nodes. The time it takes for this scanning event to occur, indeed the probability that it will occur at all, depends on many factors, including the rate that T cells and dendritic cells enter and leave the lymph node as well as the geometry of the lymph node and of course other cellular and molecular parameters. In this paper, we develop a hybrid stochastic-deterministic mathematical model at the tissue scale of the lymph node and simulate dendritic cells and cognate T cells to investigate the most important physiological factors leading to a successful and timely immune response after a vaccination. We use an agent-based model to describe the small population of cognate naive T cells and a partial differential equation description for the concentration of mature dendritic cells. We estimate the model parameters based on the known literature and measurements previously taken in our lab. We perform a parameter sensitivity analysis to quantify the sensitivity of the model results to the parameters. The results show that increasing T cell inflow through high endothelial venules, restricting cellular egress via the efferent lymph and increasing the total dendritic cell count by improving vaccinations are the among the most important physiological factors leading to an improved immune response. We also find that increasing the physical size of lymph nodes improves the overall likelihood that an immune response will take place but has a fairly weak effect on the response rate. The nature of dendritic cell trafficking through the LN (either passive or active transport) seems to have little effect on the overall immune response except if a change in overall egress time is observed. (C) 2018 Elsevier Ltd. All rights reserved.

Tags

Immune system Dynamics systems biology Lymph node Dendritic cells Immune-response Antigen presentation Lymph-nodes Motility Trafficking T-cell-activation Multiscale mathematical modelling Computational simulation Repertoire