Immune Response Template | Annotation and numerical description of immune response in humans
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Immune Response Template (IRT)

is a Quantitative Systems Pharmacology (QSP) platform of immune system and tool for development of QSP and mechanistic models related to immune response.

IRT consist of IRT Database and IRT Navigator. The core of IRT Database is IRT Core Model, a QSP model of immune system. IRT Navigator is an application software providing intuitive interface to work with IRT Database. IRT is an innovative tool allowing users to select all or any reactions and species from IRT Core Model and download it.

why irt

To learn more about IRT please sing up and try demo. Please use Google Chrome for proper work of IRT online.

To purchase access to the full version of IRT please contact us by email: irt@insysbio.com

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Latest version

Version 2.0.0. (release date: 2018-09-26)

Updates

  • General UPDATE! online access to the IRT
  • General UPDATE! constinious update of IRT Database: significant updates (new schemes, players, in vitro models, etc) 2-3 times per year + regular small updates (identification of new parameters, addition of new data, etc).
  • General UPDATE! new business model: annual subscription fee per user
  • IRT Navigator UPDATE! addition of “zoom” for schemes
  • IRT Database UPDATE! MDSC (schemes, equations, parameters, annotation): (1) introduction of monocytic MDSC (Mo-MDSC) and granulocytic MDSC (Gr-MDSC); (2) new mediators affecting MDSC maturation; (3) direct effect of MDSC on T cells functioning; (4) identification of new parameters.
  • IRT Database UPDATE! CD4 T cells (schemes, equations, parameters, annotation): (1) new state - intermediate; (2) introduction of complexes of different states of CD4 T cells with DC; (3) revision of equations describing effects of co-stimulatory and co-inhibitory receptors on CD4 T cell activation; (4) identification of new parameters; (5) removal of “in vitro” models for CD4 T cells (Th0, Th1, Th2, Th17, Treg) developed in framework of previous version of IRT.
  • IRT Database UPDATE! CD8 T cells (schemes, equations, parameters, annotation): (1) new states - intermediate, exhausted; (2) introduction of complexes of different states of CD8 T cells with DC and Target cells; (3) revision of equations describing effects of co-stimulatory and co-inhibitory receptors on CD8 T cell activation; (4) identification of new parameters; (5) removal of “in vitro” model for CD8 T cells developed in framework of previous version of IRT.
  • IRT Database UPDATE! introduction of cytokines in lymph nodes and tissue (schemes, equations, parameters, annotation).
  • IRT Database UPDATE! surface receptors description (schemes, equations, parameters, annotation): (1) new type of schemes - immunological synapse; (2) new way (in comparison with version 1.0) to describe binding of surface receptors - in framework of particular cell-cell interaction; (3) immunological synapses for CD4 and CD8 T cells vs DC, CD8 T cells vs Target cells, M1 macrophages vs Target cells; (4) identification of new parameters.
  • IRT Database UPDATE! DC (schemes, equations): (1) removal of mDC2; (2) removal of mDC from blood.
  • IRT Database NEW! addition of phenotypes for immune cells (annotation): Gr-MDSC, Mo-MDSC, resting/intermediate/activated CD4 T cells (including Th1, Th2, Th17, iTreg), resting/intermediate/activated CD8 T cells, CD56bright and CD56dim NK cells.

IRT Core Model characteristics

  • 704 reactions
  • 350 time dependent variables
  • 507 parameters - about 21% of parameters are identified
  • 293 published articles are included in IRT as references including 93 research articles from which data were extracted and used for identification of parameters or initial values of variables.

Previous versions

Version 1.0. (release date: 2016-09-01)

IRT Database

IRT Core Model composition

Compartments: blood, blood plasma, lymph nodes, inflamed tissue.

Cell types: NK cells, Dendritic cells (DC), Macrophages (M1, M2a, M2b, M2c), MDSC, B cells, CD4+ T cells (Naïve, Th1, Th2, Th17, Treg), CD8+ T cells (Naïve, CTL), Target cells.

Cytokines (presented on in blood plasma): GM-CSF, M-CSF, IFNg, TNFa, TGFb, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, IL-17(A,F), IL-18, IL-23

Surface receptors: TCR/CD3 (implicitly), MHC-I, MHC-II, CD28 (implicitly), CD80/CD86, CTLA-4, CD40 (implicitly), CD40L, PD-1, PD-L1

Other: IgG, antigen

List of main processes:

  • Antigen recognition by APC (DC, B cells);
  • Antigen presentation by APC (DC, B cells) to CD4 and CD8 T cells;
  • Licensing of APC by T cells (CD40 stimulation);
  • T cells proliferation;
  • Specific lysis of target cells by CTL (activated CD8 T cells) and NK cells;
  • Migration of cells between compartments;
  • Differentiation of monocytes into DC and macrophages;
  • Differentiation of macrophages in different types (M1, M2a, M2b, M2c);
  • IgG production by plasma cells;
  • Cytokines production by different types of the cells;
  • Differentiation of naïve CD4 T cells in Th1, Th2, Th17 and Treg cells; All these processes are regulated by cytokines and surface receptors.

IRT Core Model characteristics

  • 291 reactions
  • 79 time dependent variables
  • 310 parameters - about 30% of parameters are identified
  • about 200 published articles are included in IRT as references including about 80 research articles from which data were extracted and used for identification of parameters or initial values of variables.

“In vitro” models

There are “in vitro” models of following immune cells: B cells, CD8 T cells, dendritic cells (DC), macrophages, NK cells, monocytes, Th1 cells, Th2 cells, Th17 cells and Treg.

IRT Navigator

IRT Navigator of version 1.0.0. includes following functionality:

  • running of IRT as local application in one click in different OS (Windows, Mac OS, Linux)
  • visualization of description and annotation of IRT database components: equations, species, parameters
  • access to supplementary materials including files related to “in vitro” models, files with description of parameters calculation and estimation of initial values for species
  • navigation across multiple schemes describing different species and processes of IRT database
  • automatic generation of model template based on the user selection which can be downloaded as SBML L2/L3 file with or without full or partial annotation
  • “filter” search across whole database including interactive representation of search results on the schemes
  • various capabilities to include/exclude and check elements in the model of your choice
  • the ability to upload and continue to work with previously downloaded model template
  • generation of summary with ODE system for chosen elements

Main developers

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