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

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

Author information

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.

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

PMID:
27856216
DOI:
10.1016/j.jtbi.2016.11.008
[Indexed for MEDLINE]

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