Immunobiology models: Fibrosis and Lymph Node Cellular Dynamics
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J. Russell Butler,
Joshua T. Mattila,
Denise E. Kirschner,
Systems biology predicts that fibrosis in
tuberculous granulomas may arise through
PLoS Computational Biology (2020),
Julie Leonard-Duke, Stephanie Evans, Riley T. Hannan, Thomas H. Barker, Jason H.T. Bates, Catherine A. Bonham, Bethany B. Moore, Denise E. Kirschner, and Shayn M. Peirce,
Multi-scale models of lung fibrosis,
Matrix Biology, Available online 11 May 2020, In Press,
Hayley C. Warsinske, Amanda K. Wheaton, Kevin K. Kim, Jennifer J. Linderman, Bethany B. Moore, and Denise E. Kirschner,
Computational Modeling Predicts Simultaneous Targeting of Fibroblasts and Epithelial Cells Is Necessary for Treatment of Pulmonary Fibrosis,
Front. Pharmacol., 23 June 2016,
Warsinske, Hayley C., Ashley, Shanna L., Linderman, Jennifer J., Moore, Bethany B., Kirschner, Denise E.,
Identifying Mechanisms of Homeostatic Signaling in Fibroblast Differentiation,
Bulletin of Mathematical Biology, Sep, 2015, Springer US,
Cilfone, N, Kirschner, D and Linderman, JJ.
Strategies for Efficient numerical implementation of hybrid multi-scale agent-based models to describe biological
Cellular and Molecular Bioengineering, Nov, 2014,
Chang Gong, Jennifer J. Linderman, Denise Kirschner,
Harnessing the heterogeneity
of T cell differentiation fate to fine-tune generation of effector and memory T cells,
Front. Immunol. 5:57, 2014,
This article was one of the most viewed Frontiers in Immunology research articles in February 2014!
Frontiers top viewed immunology research articles blog
Chang Gong, Joshua T. Mattila, Mark Miller, JoAnne L. Flynn, Jennifer J. Linderman, D. Kirschner,
Predicting lymph node output efficiency through systems biology,
Journal of Theoretical Biology, Volume 335, October 21 2013, Pages 169-184, ePUB: June 29, 2013,
See http://malthus.micro.med.umich.edu/lab/movies/3dLN for movies and supplementary material.
Henry P. Mirsky, Mark J. Miller, Jennifer J. Linderman, Denise E. Kirschner,
Systems biology approaches for understanding cellular mechanisms of
immunity in lymph nodes during infection,
Journal of Theoretical Biology, Oct 21, 2011, 287:160-70, ISSN 0022-5193,
Jennifer J. Linderman, Thomas Riggs, Manjusha Pande, Mark Miller, Simeone Marino,
and Denise E. Kirschner,
Characterizing the Dynamics of CD4+ T Cell Priming within
a Lymph Node.
Journal of Immunology, 2010, 184: pp 2873-2885,
See http://malthus.micro.med.umich.edu/lab/movies/FullLN for movies and supplementary material.
Denise E. Kirschner and Jennifer J. Linderman,
Mathematical and computational approaches
can complement experimental studies of
host pathogen interactions.
Cellular Microbiology (2009) 11(4),
Thomas Riggs, Adrienne Walts, Nicolas Perry,
Laura Bickle, Jennifer N. Lynch, Amy Myers,
Joanne Flynn, Jennifer J. Linderman, Mark J. Miller,
Denise E. Kirschner,
A comparison of random vs. chemotaxis
driven contacts of T cells with dendritic
cells during repertoire scanning
Journal of Theoretical Biology (2007),
See http://malthus.micro.med.umich.edu/lab/movies/LNtzone for movies and supplementary material.
Martin J. Blaser, Denise Kirschner,
The equilibria that allow bacterial persistence in human hosts
Nature, Vol 449, j18, October 2007, pp 483-489,
Niyaz Ahmed, of the
Pathogen Evolution Laboratory, Centre for DNA Fingerprinting and
Diagnostics, India, gives his comments on the article at
This is a provocative yet legitimate proposal on how pathogenic
bacteria adapt to their co-evolved hosts across a wide array of
conditions linked to biology of both the host and pathogen, over huge
evolutionary timescales. The authors focus on the concept that
persistence represents finely negotiated, well balanced host-
microbial interests, culminating in a long-term equilibrium whose
maintenance requires a series of evolved, nested equilibria leading
to the overall homeostasis. To support their assumption the authors
harness observed pathobiology of three dreaded pathogens (H. pylori,
S. typhi and M. tuberculosis). Based on the fact that genomic and
biological features of these 'specialist' bacteria are quite diverse,
authors generalize their model for other pathogens as well. If it is
so, this model may also fit to commensals and other 'generalist'
bacteria who might have accompanied humans in various capacities
throughout their association. This dogma may therefore be relevant in
understanding acquisition and/or attenuation of virulence with the
change in human history and ecology. Although this is a largely
speculative treatise, I am sure it will provide a foundation for
future experimental evidence.
Raymond Mejia, of the
National Heart, Lung and Blood Institute (NHLBI),
and the National Institutes of Health (NIH),
gives his comments on the article at
This study uses a mathematical model to explain bacterial persistence
in a host population. Symbiosis is characterized by existence of
evolutionary stable states that permit homeostasis. The model is applied
to three bacteria with human hosts, H. pylori, S. typhi, and M. tuberculosis,
and can be utilized to investigate how virulence may vary with changes in human ecology.
Denise E. Kirschner,
Stewart T. Chang,
Thomas W. Riggs,
Jennifer J. Linderman,
Toward a multi scale model of antigen
presentation in immunity,
Immunological Reviews 2007
Vol. 216:,pp. 93-118, PMID: n/a, PMCID: n/a, NIHMSID: n/a
Simeone Marino, Edoardo Beretta, and Denise E. Kirschner
The Role of Delays in Innate and Adaptive Immunity
to Intracellular Bacterial Infection,
Mathematical BioSciences and Engineering, Volume 4, Number 2,
April 2007, pp. 261-286, PMID: 17658927, PMCID: (exempt).
Edoardo Beretta, Margherita Carletti, Denise E. Kirschner, and Simeone Marino
Stability Analysis of a Mathematical Model of the Immune Response
177-206, Mathematics for Life Science and Medicine, Springer-Verlag Berlin Heidelberg,
2007, PMID: n/a, PMCID: (exempt).
The Multi-scale Immune Response to Pathogens:
M. tuberculosis as an Example,
In Silico Immunology,
PMID: n/a, PMCID: (exempt).
Penelope A. Morel, Shlomo Ta'asan, Benoit F. Morel, Denise E. Kirschner, and Joanne L. Flynn
New Insights into Mathematical Modeling of the Immune System
Immunologic Research, Vol. 36, Issue 1-3, pp:157-165, 2006, PMID: 17337776, PMCID: n/a, NIHMSID: n/a.
Chang, ST, Ghosh, D, Kirschner, D and Linderman, JL.
Peptide length-based prediction of peptide-MHC class II binding.
Bioinformatics, 22:2761-2767, 2006, PMID: 17000752, PMCID: n/a, NIHMSID: n/a.
J. Christian J Ray and Kirschner. D.
Requirement for multiple activation signals by anti-inflammatory
feedback in macrophages
Journal of Theoretical Biology , 241(2), pp. 276-294. 2006, PMID: 16460764, PMCID: n/a, NIHMSID: n/a.
Segovia-Juarez, J, S. Colombano, Kirschner, D
Identifying DNA splice sites using hypernetworks with artificial
Biosystems, Volume 87, February 2007, Pages 117-124, PMID: 17116361, PMCID: n/a, NIHMSID: n/a.
Stewart T. Chang, Jennifer J. Linderman, and Denise E. Kirschner
Multiple mechanisms allow Mycobacterium
tuberculosis to continuously inhibit MHC class
II-mediated antigen presentation by macrophages
4530 4535 PNAS March 22, 2005 vol. 102 no. 12, PMID: 15767567, PMCID: PMC555518, NIHMSID: n/a.
Simeone Marino, Suman Ganguli, Ian Joseph, and Denise Kirschner
The Importance of an Inter-compartmental Delay in a Model for Human Gastric Acid Secretion
, Bulletin of Mathematical Biology (2003) 00, 1-28,
PMID: 14607284, PMCID: n/a, NIHMSID: n/a.
Ping Ye and Denise E. Kirschner
Measuring Emigration of Human Thymocytes by T-Cell Receptor Excision Circles.
Critical Reviews in Immunology, 22(5&6):483 498 (2002), PMID: 12803323, PMCID: n/a, NIHMSID: n/a.
Ping Ye and Denise E. Kirschner, Reevaluation of T Cell Receptor Excision Circles as
a Measure of Human Revent Thymic Emigrants J. Immunology
168, 10, 2002, PMID: 11994448, PMCID: n/a, NIHMSID: n/a.
Denise E. Kirschner, Reconstructing Microbial Pathogenesis
ASM News Vol 67, Numer 11, 2001, PMID: n/a, PMCID: n/a, NIHMSID: n/a.
Jorge X. Velasco-Hernandez, Jose A. Garcia, Denise E. Kirschner
, Remarks on Modeling
Host-Viral Dynamics and Treatment. in: Volume 125: Mathematical
Approaches for Emerging and Reemerging Infectious Diseases Part I: An Introduction
to Models, Methods, and Theory
Editors: Carlos Castillo-Chavez with Sally Blower, Pauline van den Driessche,
Denise Kirschner, and Abdul-Aziz Yakubu, 2001, PMID: n/a, PMCID: n/a, NIHMSID: n/a.
Wigginton J and Kirschner D. A model of cellular immune regulation in infection with
Mycobacterium tuberculosis, Journal of Immunology, Feb 2001, PMID: 11160244, PMCID: n/a, NIHMSID: n/a.
Kirschner D, Webb GF and Cloyd M. A model of HIV-1 disease progression based on virus-induced
lymph node homing and homing-induced apoptosis of CD4+ T lymphocytes.
J. AIDS & Human Retrov vol 23, pps. , August 2000, PMID: 11015152, PMCID: n/a, NIHMSID: n/a.
Covert D and Kirschner D. Revisiting the early models of the host-pathogen interactions
in HIV infection, Comments on Theoretical Biology Vol 5(6)
pp. 383-411, 2000, PMID: n/a, PMCID: n/a, NIHMSID: n/a.
Blaser MJ and Kirschner D. Dynamics of Helicobacter pylori colonization in relation
to the host immune response. PNAS, 96:8359-8364, 1999, PMID: 10411880, PMCID: PMC17522, NIHMSID: n/a.
Kirschner D and Panetta JC. Modeling immunotherapy of the tumor-immune interaction.
J Math Biol, 37: 235-252, 1998,
PMCID: n/a, NIHMSID: n/a.
Kirschner D and Webb GF. Immunotherapy of HIV-1 infection. J Biol
Systems, 6:71-83, 1998, PMID: n/a, PMCID: n/a, NIHMSID: n/a.
Kirschner D, Mehr R and Perelson A. The role of the thymus in pediatric HIV-1 infection.
J AIDS & Human Retrov, 18:95-109, 1998, PMID: 9637574, PMCID: n/a, NIHMSID: n/a.
Kirschner D and Webb GF. A model for treatment strategy in the chemotherapy of
AIDS. Bull Math Biol 58:367-390, 1996, PMID: 8713663, PMCID: n/a, NIHMSID: n/a.
Perelson A, Kirschner D, De Boer R. The dynamics of HIV infection of CD4+ T cells.
Math Biosci 114:81-125, 1993, PMID: 11517319, PMCID: PMC56941, NIHMSID: n/a.