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Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

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Time course of Abs, CTLs, and IFN.The time courses predicted by models (top row) and experimentally determined time courses (bottom row) for Abs (left), CTLs (centre), and IFN (right). All data has been scaled to peak at 1.0. Experimental data are collected from mice unless otherwise indicated.
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pone-0057088-g007: Time course of Abs, CTLs, and IFN.The time courses predicted by models (top row) and experimentally determined time courses (bottom row) for Abs (left), CTLs (centre), and IFN (right). All data has been scaled to peak at 1.0. Experimental data are collected from mice unless otherwise indicated.

Mentions: In addition to examining the models' predictions of the infection process in the absence of various immune components, we also consider whether the models accurately replicate the time course of the immune response itself. Fig. 7 compares the levels of Abs, CTLs, and IFN over the course of an influenza infection observed experimentally to those predicted by the mathematical models.


Assessing mathematical models of influenza infections using features of the immune response.

Dobrovolny HM, Reddy MB, Kamal MA, Rayner CR, Beauchemin CA - PLoS ONE (2013)

Time course of Abs, CTLs, and IFN.The time courses predicted by models (top row) and experimentally determined time courses (bottom row) for Abs (left), CTLs (centre), and IFN (right). All data has been scaled to peak at 1.0. Experimental data are collected from mice unless otherwise indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585335&req=5

pone-0057088-g007: Time course of Abs, CTLs, and IFN.The time courses predicted by models (top row) and experimentally determined time courses (bottom row) for Abs (left), CTLs (centre), and IFN (right). All data has been scaled to peak at 1.0. Experimental data are collected from mice unless otherwise indicated.
Mentions: In addition to examining the models' predictions of the infection process in the absence of various immune components, we also consider whether the models accurately replicate the time course of the immune response itself. Fig. 7 compares the levels of Abs, CTLs, and IFN over the course of an influenza infection observed experimentally to those predicted by the mathematical models.

Bottom Line: Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions.We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed.Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Texas Christian University, Fort Worth, Texas, USA.

ABSTRACT
The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.

Show MeSH
Related in: MedlinePlus