[SwarmFest2004] SwarmFest 2004 Abstract

[Jose L Segovia-Juarez]

Dear SwarmFest2004 Organizing Committee:

  We are submitting the following abstract to
be considered for a talk at SwarmFest 2004.

Title: "An agent-based model to study tuberculosis granuloma
        formation in the lung".

Authors: Jose L. Segovia-Juarez(1), Suman Ganguli(2), and
         Denise Kirschner(1)

(1) Department of Microbiology and Immunology, University of Michigan,
    Ann Arbor, MI 48109, USA.
(2) Biosystems Group, Department of Biopharmaceutical
    Sciences, University of California San Francisco, San Francisco, CA
    94143, USA.

  Best regards,

Jose

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ABSTRACT

An agent-based model to study tuberculosis granuloma formation in the lung

Jose L. Segovia-Juarez(1), Suman Ganguli(2), and Denise Kirschner(1)

(1) Department of Microbiology and Immunology, University of Michigan,
    Ann Arbor, MI 48109, USA.
    http://malthus.micro.med.umich.edu/lab/

(2) Biosystems Group, Department of Biopharmaceutical
    Sciences, University of California San Francisco, San Francisco, CA
    94143, USA.


Infection with Mycobacterium tuberculosis is a major world health
problem. An estimated 2 billion people are presently infected and the
disease causes approximately 3 million deaths per year. After bacteria
are inhaled into the lung, a complex immune response is triggered
leading to the formation of multicellular structures called
granulomas.  The understanding of granuloma formation in the lung is
key for improving diagnostic and treatment of the disease. There are
several cells types and chemical factors involved in granuloma
formation: macrophages, CD4 and CD8 T-cells, several chemokines and
cytokines. We have developed an agent-based model to study this
complex biological system.  The model, implemented in C++, combines
continuous representations of chemokines, and discrete representation
of macrophages, T-cells in a cellular automata like environment.  A
two dimensional array represents the lattice. Each element of the
array contains macrophages, T cells, chemokine and bacteria.  Objects
were created for macrophages and T cells. Real variables were used for
extracellular bacteria and chemokine concentrations. We established a
set of rules to govern the dynamics of the system, representing the
biological interactions of the entities. Our results indicate that key
host elements involved in granuloma formation are chemokine diffusion,
macrophage overcrowding the granuloma, number of T cells within the
granuloma, and an overall host ability to activate macrophages.



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