Modelling Factor H Mediated Self vs. Non-self Discrimination

Factor H is a versatile and most abundant regulator of the alternative pathway of the complement system. Factor H reduces the opsonization of the cell surface and inhibits the amplification of complement activation on the cell surface. Using the DynaCoSys model, the influence of Factor H on the cell surface is investigated.

Experimental Collaborators

Relative coverage (A) and proportion (B) of C3b molecules at the cell surface

Based on the dominating types of $C_3b$ molecules, we distinguish the two extreme regimes for non-self recognition and self-tolerance that are separated by a transition regime where complement evasion takes place.

The steady state of the system illustrates that Factor H is crucial for the level of complement molecule concentration on the cell surface. Using the ratio of complement molecules on the cell surface, we show that Factor H is crucial for discrimination between self and non-self cells. Furthermore, we could identify a regime of complement evasive pathogens.

Steady states of the molecules C3bf and C3af in the fluid phase for varying surface-bound Factor H concentrations

(A) Radial steady state concentration profile of the fluid-phase $C_3b^f$ concentration. (B) Radial steady state concentration profile of the fluid-phase $C_3a^f$ concentration. Mind the different scales in (A,B).

With the partial differential equations, it is possible to analyze in detail the concentration of active opsonins and anaphylatoxins around the cell surface.

Publications

Posters

12333 Next