Abstract:
We develop a mathematical framework for modeling regulatory mechanisms
in
the adaptive immune system. The model describes dynamics of several
components of the immune system, including effector and regulatory T
cells, antigen-presenting cells, and cell signaling. The model also
incorporates two key microenvironments: the lymph node and the tissue.
The model captures three features of the dynamics and regulation of
the
primary adaptive response: 1) Transition between expansion and
contraction
phases of the immune response, 2) Self/non-self discrimination, and 3)
T
cell traffic between the lymph node and tissue during the course of
the
primary response. All three of these self-regulatory mechanisms are
mediated in large part by regulatory T cells.
In this talk, we focus primarily on deepening our understanding the
first
point, namely the timely transition between expansion and contraction
phases. In trying to unravel the mechanism behind a normal, healthy T
cell response, we draw connections to the behavior of other well-known
excitable systems studied in molecular biology and physiology.
Although various computational models exist, the fundamental dynamics
of
immune regulation still remains unexplained, so in closing, we propose
a
few potential approaches to unraveling this mystery.