Modelagem computacional da formação de abscessos

Abstract

In some bacterial infections, the immune system is not capable of completely eliminating the invading pathogen. In these cases, the invading pathogen is successful in establishing a favorable enviroment to survive and persist in the host organism. The pathogens employ different strategies to survive in the host. Among these strategies, we can highlight: human immunodeficiency virus infects T CD4+ cells that are very important in the adaptive immune response, causing a suppression of this response; bacteria Mycobacterium tuberculosis persist in the host organism through the intracellular infection of macrophages; bacteria Staphylococcus aureus persist in the host through the production of a fibrin network that acts as a protecting barrier against the innate immune response. In the case of Staphylococcus aureus and other bacteria species, the formation of a fibrin network together with other mechanisms as, for instance, the secretion of toxins give rise to a lesion known as abscess. An abscess is characterized as an area comprising bacteria, cells of the immune system (mainly neutrophils) and many types of dead cells. The abscess formation can be seen as the result of a series of strategies employed by bacteria to escape the immune response and to establish a favorable enviroment to persist in the host. This work has the objective of reproducing some characteristics of the process of abscess formation through computational simulations. The computational simulations are based in mathematical models of partial differential equations. The mathematical models presented in this work were developed through an incremental approach. In this approach the modeling process is initiated with the development of a simplified model that is capable of reproducing some behavior of the phenomena of interest and then this model can be extended through the addition of other variables and processes. The hypotheses, the variables, the relation between variables and the processes considered in the mathematical models of this work were constructed based on a study that was conducted about fisiopathology of the abscess, envolving contact with experts of the experimental area (microbiologists, imunologists and medical doctors), reading of the literature and analysis of experimental data. The models developed in this work were capable of reproducing some characteristics observed experimentaly as, for example, the formation of a bacteria colony in the central region of the abscess, surrounded by a fibrin network. Surrounding the fibrin network, it was observed an accumulation of dead neutrophils and healthy neutrophils as in the experimental data. These models were also capable of reproducing some characteristics observed in the in vivo experiment of immune response depletion as, for example, an increase in the number of abscesses, with some abscesses containing high concentrations of bacteria and fibrin.