Quantification of Factor H Mediated Self vs. Non-self Discrimination by Mathematical Modeling

Area of Science:

• Immunology
• Computational Biology
• Biophysics

Background:

• The complement system is crucial for innate immunity, mediating pathogen opsonization and phagocytosis.
• Tight regulation by Factor H is essential to prevent self-cell damage from complement activation.
• Pathogens can evade immune detection by binding Factor H, leading to severe infections.

Purpose of the Study:

• To develop a mathematical model (DynaCoSys) for quantitatively analyzing complement system dynamics.
• To predict conditions of Factor H-mediated complement evasion by pathogens.
• To identify key regulatory processes in complement activation for self and non-self cells.

Main Methods:

• Developed a hybrid mathematical model (DynaCoSys) using ordinary and partial differential equations.
• Modeled complement cascade focusing on C3b dynamics in fluid and cell-surface phases.
• Performed sensitivity analysis to identify critical model parameters and driving processes.

Main Results:

• Quantitatively predicted conditions for Factor H-mediated complement evasion.
• Identified critical Factor H concentration threshold distinguishing self and non-self regimes.
• Determined the differential impact of model parameters on this threshold.

Conclusions:

• The DynaCoSys model provides quantitative insights into complement activation and regulation.
• Understanding Factor H's role is crucial for pathogen evasion and associated diseases like renal and retinal conditions.
• The model can be extended for evaluating therapeutic strategies for complement-related disorders.