Category Cross-Omics>Agent-Based Modeling/Simulation/Tools

Abstract C-ImmSim is an Agent-Based Model (ABM), hence cells are represented as agents, i.e., they keep their individual experience throughout their simulated life span. Cells interact locally (i.e., inside a lattice site).

Major classes of cells of the lymphoid lineage (lymphocytes T helper, TH, and cytotoxic, CTL, lymphocytes B and deriving antibody-producing plasma cells, PLB) and some of the myeloid lineage (macrophages, MA, and dendritic cells, DC) are considered.

C-ImmSim is a 'polyclonal model' since an arbitrary repertoire size of lymphocytes can be represented (as opposed to the 'monoclonal models' where only a single population of genetically identical lymphocytes is represented).

Lymphocytes are created in the bone marrow compartment. While B lymphocytes go into circulation directly, the T lymphocytes pass through the Thymus where they undergo selection for auto reactive cells.

The mobility of cells is modeled by taking into account realistic diffusion coefficients observed in vivo. T cells have a faster diffusion constant than B cells.

Moreover, in absence of chemotaxis, macrophage and dendritic cells have diffusivity similar to B cells.

Molecules, instead, (like IL2, D signal, etc.) diffuse much faster than both T and B cells but their effective displacement and interaction capability is limited by their half-life and their concentration.

Chemotaxis is modeled in a quite simple way, that is, by having the cells to move (on average) in the direction of the higher gradient of the chemotactic agent c(x,t) at position x at time t.

Affinity --

Two bit-strings complement each other (or are a perfect match) if every 0 in one corresponds to a 1 in the other and conversely. More generally, an m-bit match is defined as a pair where exactly m bits complement each other.

The affinity is then defined as a monotonic function of m; higher m the more likely for the two strings to bind. The affinity also includes a cut-off; for matching smaller than this threshold value, No binding occurs.

Homeostasis --

Homeostasis is implemented by a means of a mean reverting process. This is used to calculate how many cells, for each cell type, are to be created at each time step, or, how many cells have to be eliminated.

The actual deletion of the cells from the simulation is made stochastically by taking into account their individual half-life.

Peptide digestion and presentation --

C-ImmSim implements peptide digestion and presentation of peptides on both MHC class I and class II molecules (exogenous and endogenous pathways).

Since MHC molecules are also represented as binary strings, the MHC- peptide binding is also modeled through a function of the matching bits in the bit string comparison.

Immune memory --

In C-ImmSim the manufacturer considers the memory as a "cell’s state" acquired during active participation to successive (and successful) immune responses.

The manufacturer models the memory of lymphocytes by a mechanism that increases the half-life of a cell by a certain amount every time those cells participate in a successful interaction.

The rationale behind this modeling choice is that useful cells survive longer than useless simply because they get a whole lot of stimulations during the immune reactions.

The overall result of this process is that few cells increase their half-life considerably and live longer than other cells.

Moreover, in this way, the manufacturer obtains an expansion of the memory compartment that is somehow proportional (in a non linear way, to be correct) to the magnitude of the infection and consequent duration of the immune response.

On top of the basic mechanisms/features of the cellular dynamics described above, C-ImmSim incorporates quite a few additional working assumptions/theories (some of them can be easily toggled on/off; others require a complete rethinking of the model).

These are as follows:

1) Clonal selection theory.

2) Thymus education of T lymphocytes (clonal deletion theory).

3) Hypermutation of antibodies.

4) Hayflick limit (T cells replicative senescence).

5) Anergy.

6) T cell Anergy.

7) Ag-dose induced tolerance (Anergy) in B cell.

8) Matzinger’s danger signals.

9) Idiotypic Network theory.

System Requirements

C-ImmSim can be compiled on any Unix-like machine (Linux, MacOS, etc.) that has auto-configure capabilities. It can also be compiled under Windows by using Makefile.win included in the package.


Manufacturer Web Site C-ImmSim

Price Contact manufacturer.

G6G Abstract Number 20447

G6G Manufacturer Number 104075