A Monte Carlo Simulation for the Construction of Cytotoxic T Lymphocytes Repertoire

Abstract

The immune system of vertebrate living beings is a very complicated system that has evolved a set of mechanisms to get rid of potential pathogens he get in contact with. These mechanisms are so finely tuned that we don’t even realize how much work our immune defenses are carrying out each moment to keep us disease free. Unfortunately, as one can figure, the whole system is not error free. For example, autoimmune diseases arise when at least one of the mechanisms meant to preserve tolerance of self breaks. The immune self tolerance is the process by which the immune system refrain fromattaching the host own body. This is normally the norm but given the huge complexity of the interdependencies among immune components (cells, molecules, organs, signals, etc.), and also given that the immune defenses are not static but rather dynamic and ever changing during our lifetime, it should not be surprising to learn of the different autoimmune diseases known to date. Tolerance is the evolutionary result of a multi-layer system whose goal is to weed out self-reactive cells. Of these mechanisms, lymphocytes T education in the thymus organ represents the very first one. In this article we describe a Monte Carlo method to simulate the maturation of key immune cells. Before describing the algorithm we give a brief introduction of how the immune system works. The goal of the present work is purely methodological. In fact, while we focus on the specific aspect of the examination phase of the T lymphocytes maturation, we use immuno-informatics data and methods to perform computer simulation of the whole process without taking into account, for example, the anatomical structure of the thymus organ where the process of lymphocytes education takes place. Moreover, for reasons that will be mentioned later, we will specifically deal with CD8+ T-cells (i.e., CTLs) selection rather than on CD4+ T-cells (T helpers).