Visceral leishmaniasis (also called "Kala-azar") is a widespread disease, which is usually fatal in the absence of treatment. Characteristic of the liver immune response to leishmaniasis is a type of inflammation (granulomatous inflammation) that leads to the formation of "granulomas". A granuloma provides a very interesting micro-environment, which is maintained by the coordination of many cells of the immune system. Due to the complexity of the immune response, only a limited amount of modeling work exists in the context of granulomatous infection, and most of the current models focus only on the formation stage of granulomas. The primary goal of this thesis is to gain insights into the process of formation and development of a granuloma. To this end, we built a model of the granuloma formation and resolution in the liver using stochastic Petri nets, and performed several in silico experiments to study the nature of the immune response to leishmaniasis, possible therapeutic options, and the role of the cells involved. Additionally, the building of the model is extensively documented, and the most important qualitative and quantitative assumptions are referenced and discussed, with the aim of presenting a “conceptual framework” to be used when facing similar problems. The model is validated against available biological data, and its robustness is assessed using sensitivity analysis.

A PETRI NET MODEL OF LIVER RESPONSE TO VISCERAL LEISHMANIASIS: SELF-REGULATION AND COMPLEX INTERPLAY IN THE VERTEBRATE IMMUNE SYSTEM / L. Albergante ; supervisor: Jon Timmis ; co-supervisor: Giovanni Naldi ; ph.d. program director: Vincenzo Capasso. Universita' degli Studi di Milano, 2010 Dec 17. 22. ciclo, Anno Accademico 2009. [10.13130/albergante-luca_phd2010-12-17].

A PETRI NET MODEL OF LIVER RESPONSE TO VISCERAL LEISHMANIASIS: SELF-REGULATION AND COMPLEX INTERPLAY IN THE VERTEBRATE IMMUNE SYSTEM

L. Albergante
2010

Abstract

Visceral leishmaniasis (also called "Kala-azar") is a widespread disease, which is usually fatal in the absence of treatment. Characteristic of the liver immune response to leishmaniasis is a type of inflammation (granulomatous inflammation) that leads to the formation of "granulomas". A granuloma provides a very interesting micro-environment, which is maintained by the coordination of many cells of the immune system. Due to the complexity of the immune response, only a limited amount of modeling work exists in the context of granulomatous infection, and most of the current models focus only on the formation stage of granulomas. The primary goal of this thesis is to gain insights into the process of formation and development of a granuloma. To this end, we built a model of the granuloma formation and resolution in the liver using stochastic Petri nets, and performed several in silico experiments to study the nature of the immune response to leishmaniasis, possible therapeutic options, and the role of the cells involved. Additionally, the building of the model is extensively documented, and the most important qualitative and quantitative assumptions are referenced and discussed, with the aim of presenting a “conceptual framework” to be used when facing similar problems. The model is validated against available biological data, and its robustness is assessed using sensitivity analysis.
17-dic-2010
Settore INF/01 - Informatica
Stochastic Petri Net ; Vischeral Leishmaniasis ; Granuloma ; Vertebrate Immune System ; Natural Killer T Cell ; Natural Killer Cell ; Kupffer Cell ; Macrophage Activation ; Partial Rank Correlation Coefficients ; T cell ; Leishamania Donovani
TIMMIS, JON
NALDI, GIOVANNI
Doctoral Thesis
A PETRI NET MODEL OF LIVER RESPONSE TO VISCERAL LEISHMANIASIS: SELF-REGULATION AND COMPLEX INTERPLAY IN THE VERTEBRATE IMMUNE SYSTEM / L. Albergante ; supervisor: Jon Timmis ; co-supervisor: Giovanni Naldi ; ph.d. program director: Vincenzo Capasso. Universita' degli Studi di Milano, 2010 Dec 17. 22. ciclo, Anno Accademico 2009. [10.13130/albergante-luca_phd2010-12-17].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/150085
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