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lack of costimulation from antigen presenting cells (APCs). There is, however, a
dominant mechanism [3], based on active downregulation of the activation and
expansion of self-reactive lymphocytes by certain T cells [4], named regulatory
T cells.
In addition, as discussed in [5], there's not much information regarding the
mechanisms that terminate immune responses. After a response to an antigen,
the immune system is returned to a state of rest, just like before the initiation
of the response. This process, called homeostasis, allows the immune system
to respond to new antigenic challenges (because the lymphocyte repertoire is
closely regulated), and is also conducted by regulatory T cells.
To understand how the control of an initiated immune response is important,
it is interesting to notice that, according to [6], the tissue damage that follows
the chronic inflamation of tuberculosis is caused not by the bacillus, but by an
uncontrolled response to it. In this sense, this work presents a model for the
control of an initiated immune response, based on regulatory cells and cytokine
secretion and absorption. The model has been motivated by the hypothesis that
the same cytokine that improves an initiated response can lead to its termination,
if this cytokine acts on more than one cell type with different anities.
This paper is presented in the following way: first a short description of the
cytokines included in the proposed model is presented. Afterwards, regulatory
T cells are discussed, focusing on their interesting features for the simulation,
followed by a detailed description of the proposed model and its parameters. In
the end, results obtained by a simulation are presented and discussed.
2Cytokins
Cytokines are control proteins secreted by the cells of the immune system, in
response to microbes, other antigens or even other cytokines. For greater details
regarding cytokines, the reader is invited to read [7] and [8].
Most cytokines are pleiotropic (capable of acting on different cell types), and
influence the synthesis and actions of other cytokines. Besides, their secretion is
a brief, self-limited event, and they may have local and systemic actions. They
usually act close to where they are produced, either on the same cell that se-
cretes them (autocrine action) or on a nearby cell (paracrine action), and initiate
their actions by binding to specific receptors located on the membrane of the
target cells. The expression of these receptors (and, thus, the responsiveness to
cytokines) is controlled by external cell signals (in B and T cells, the stimulation
of antigen receptors). In the proposed model, there are two cytokines of interest,
described below:
Interferon-
γ
(IFN-
γ
):
IFN-
γ
is the cytokine that allows T lymphocytes and
natural killer (NK) cells to activate macrophages to kill phagocytosed patho-
gens. Besides, IFN-
γ
improves the ability of antigen presenting cells (APCs)
to present antigens, by increasing the expression of MHC and costimulation
molecules. Therefore, it can be seen as an stimulation cytokine, that acts in
order to increase the magnitude of a response;
