Dataset Information

Palsson2013 - Fully-integrated immune response model (FIRM)

ABSTRACT: Palsson2013 - Fully-integration immune response model (FIRM) FIRM (The Fully-integrated Immune Response Modeling) is a hybrid construct incorporating multiple existing models of the immune system [De Boer et al., (1985);Bell, (1970); Marino and Kirschner, (2004) ]. FIRM used a pharmacokinetic / pharmacodynamic modelling approach to combine previously published individual models of humoral and cellular response with antigen exposure. This integrated model has a potential to simulate a range of responses under a variety of conditions, for example, the immune response against tuberculosis infection, blood borne pathogen infection, Spontaneous tumour rejection and influence of regulatory T cells (Treg) on tumour rejection. The SBML model provided here was generated from the matlab code (provided by the authors). The matlab to SBML conversion was done using MOCCASIN version 1.1.0. This model describes the immune response against tuberculosis (TB) infection and reproduces figure 7 of the reference publication. Note:The following minor edit to the original matlab code was done during the conversion to SBML: The model had two parameters named k3 and K3. To avoid case-insensitive issues during the conversion, K3 was changed to K3s in the original matlap code before using the conversion software. The matlab code of the model provided by the authors (with the above change) can be obtained from the curation tab. This model is described in the article: The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models. Palsson S, Hickling TP, Bradshaw-Pierce EL, Zager M, Jooss K, O'Brien PJ, Spilker ME, Palsson BO, Vicini P. BMC Syst Biol. 2013 Sep 28;7:95. Abstract: BACKGROUND: The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but rarely have they been proposed to encompass the overall system complexity. We propose here a framework for integration of subset models, based on a system biology approach. RESULTS: A dynamic simulator, the Fully-integrated Immune Response Model (FIRM), was built in a stepwise fashion by integrating published subset models and adding novel features. The approach used to build the model includes the formulation of the network of interacting species and the subsequent introduction of rate laws to describe each biological process. The resulting model represents a multi-organ structure, comprised of the target organ where the immune response takes place, circulating blood, lymphoid T, and lymphoid B tissue. The cell types accounted for include macrophages, a few T-cell lineages (cytotoxic, regulatory, helper 1, and helper 2), and B-cell activation to plasma cells. Four different cytokines were accounted for: IFN-γ, IL-4, IL-10 and IL-12. In addition, generic inflammatory signals are used to represent the kinetics of IL-1, IL-2, and TGF-β. Cell recruitment, differentiation, replication, apoptosis and migration are described as appropriate for the different cell types. The model is a hybrid structure containing information from several mammalian species. The structure of the network was built to be physiologically and biochemically consistent. Rate laws for all the cellular fate processes, growth factor production rates and half-lives, together with antibody production rates and half-lives, are provided. The results demonstrate how this framework can be used to integrate mathematical models of the immune response from several published sources and describe qualitative predictions of global immune system response arising from the integrated, hybrid model. In addition, we show how the model can be expanded to include novel biological findings. Case studies were carried out to simulate TB infection, tumor rejection, response to a blood borne pathogen and the consequences of accounting for regulatory T-cells. CONCLUSIONS: The final result of this work is a postulated and increasingly comprehensive representation of the mammalian immune system, based on physiological knowledge and susceptible to further experimental testing and validation. We believe that the integrated nature of FIRM has the potential to simulate a range of responses under a variety of conditions, from modeling of immune responses after tuberculosis (TB) infection to tumor formation in tissues. FIRM also has the flexibility to be expanded to include both complex and novel immunological response features as our knowledge of the immune system advances. This model is hosted on BioModels Database and identified by: MODEL1603310000. To cite BioModels Database, please use: BioModels: Content, Features, Functionality and Use. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

DISEASE(S): Tuberculosis

SUBMITTER: Vijayalakshmi Chelliah

PROVIDER: BIOMD0000000608 | BioModels | 2016-04-19

REPOSITORIES: BioModels

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The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models.

Palsson Sirus S Hickling Timothy P TP Bradshaw-Pierce Erica L EL Zager Michael M Jooss Karin K O'Brien Peter J PJ Spilker Mary E ME Palsson Bernhard O BO Vicini Paolo P

BMC systems biology 20130928

<h4>Background</h4>The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but ra ...[more]

PMID: 24074340

Publication: 1/4

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Dataset Information

Palsson2013 - Fully-integrated immune response model (FIRM)

Publications

The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models.

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