Speaker
Description
Immune reactions are governed by highly complex molecular mechanisms. Because of the
high complexity of the biological data, it is often difficult to unravel these molecular
mechanisms. A systems biology approach consisting of a combination of mathematical
modeling and quantitative biological experimentation promises deeper insights into the
processes of living system.
In this study, we focus on the alternative pathway of the human complement system,
which is part of the innate immune response and detects, opsonizes and eleminates
pathogens. The destruction of host cells is inhibited through human complement
regulators, such as factor H which are present in blood plasma and can be bound to cell
membranes.
The complement system can be described as a cascade of reactions which can be
described by a system of first-order differential equations. The model focuses on the most
important components of the complement cascade: C3b in the fluid phase and on the cell
surface as well as inactivated C3b on the cell surface. The other components of the
complement system are combined in effective rates that model the dynamics of the
formation of several intermediate products of the cascade. The solution of the steady state
of the system reveals two domains were host cells and microbial cells are differently
treated, depending on the concentration of the complement inhibitor factor H on the cell
surface.
The solution of this system shows that the ability of binding factor H is crucial for survival
of cells in the host system. In addition, the immune evasion strategy of pathogens that bind
additional factor H to their surface can be explained mathematically in this way.
