Tuberculose: estudo da formaÃÃo de padrÃes na eliminaÃÃo, contenÃÃo e disseminaÃÃo do bacilo de Koch

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Tuberculosis (TB) is an endemic disease caused by an aerobic bacterium named Mycobacterium tuberculosis (Mtb). It is responsible for on third of population infected worldwide and it causes 2.2 millions deaths per year. The most common infection by Mtb occurs by inhalation of microorganisms into the lungs, where they infect mainly alveolar macrophages. The infected macrophages release cytokines activating the specific immune that results in the development of a granulomatous structure built by immune cells (macrophages, T and B cells) at the site of infection. The granuloma controls the dissemination of bacteria into the lungs by controlling its replication. Despite all the efforts and studies performed until now to understand the dynamics of the granuloma formation, the mechanisms underlying its growth and its stability are still unknown. In this thesis we introduce a mathematical model based on a cellular automata approach, to describe the granuloma formation as an immune response to Mtb and the different outcomes resulting from its dynamics that are observed in nature. The model takes into account the main cells involved in the immune response to Mtb, as well as its activation and/or migration due to the influence of chemokine and cytokine signaling. Depending on the region of the parameter space, the model reproduces at least one of the tree dynamical behaviours observed in animal models: elimination, contention and dissemination. The model reproduces also experimental results obtained in experiments performed with mice: the time evolution of T cells and bacteria counts during the dynamics of contention. In this thesis we also analyse the characteristics of a complex network obtained from a previous study of the tuberculosis endemic processes, which was conducted by other members of our group. Two types of network were obtained from the analysis of the space-time correlation among the annual new TB cases occurring in Olinda, a town of the Northeast of Brazil, during two different periods of five consecutive years: the topological ones where the endemic process take place along the periods and the weighted networks in which the weights are attributed to the nodes and correspond to the number of cases that occurred in each node for each period of five years. By studying the behaviour of the usual quantities defined for complex networks, we show that the topological networks extracted from the endemic process exhibit the properties of a small world networks. However when we associate weights to the nodes, the networks exhibit scale-free properties.

ASSUNTO(S)

ttuberculose redes complexas tuberculosis granuloma immune system autÃmatos celulares granuloma cellular automata fisica complex networks sistema imunolÃgico

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