Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

Ada W C Yan; Pengxing Cao; Jane M Heffernan; Jodie McVernon; Kylie M Quinn; Nicole L La Gruta; Karen L Laurie; James M McCaw

doi:10.1016/j.jtbi.2016.11.008

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

J Theor Biol. 2017 Jan 21:413:34-49. doi: 10.1016/j.jtbi.2016.11.008. Epub 2016 Nov 15.

Authors

Ada W C Yan¹, Pengxing Cao¹, Jane M Heffernan², Jodie McVernon³, Kylie M Quinn⁴, Nicole L La Gruta⁴, Karen L Laurie⁵, James M McCaw⁶

Affiliations

¹ School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
² Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada M3J 1P3; Modelling Infection and Immunity Lab, Centre for Disease Modelling, York Institute for Health Research, York University, Toronto, Ontario, Canada M3J 1P3.
³ Doherty Epidemiology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3010, Australia; Modelling and Simulation, Infection and Immunity Theme, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
⁴ Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
⁵ WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; School of Applied and Biomedical Sciences, Federation University, Churchill, VIC 3842, Australia; Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia.
⁶ School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC 3010, Australia; Modelling and Simulation, Infection and Immunity Theme, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia. Electronic address: jamesm@unimelb.edu.au.

PMID: 27856216
DOI: 10.1016/j.jtbi.2016.11.008

Abstract

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.

Keywords: Cytotoxic T lymphocyte; Immunology; Mathematical model; Viral dynamics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity*
CD8-Positive T-Lymphocytes / immunology
Cross Reactions / immunology*
Epitopes / immunology
Host-Pathogen Interactions / immunology*
Humans
Immunity, Cellular*
Immunologic Memory*
Influenza, Human / immunology*
Models, Immunological*
Viral Load / immunology

Substances

Epitopes