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Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
Published on: January 29, 2014
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Quantitative Modeling of the Alternative Pathway of the Complement System
Nehemiah Zewde1, Ronald D Gorham1, Angel Dorado2
1Department of Bioengineering, University of California Riverside, Riverside, California, United States of America.
Plos One
|April 1, 2016
Summary
This study presents a quantitative model of the complement system's alternative pathway, revealing its robust activation on pathogens and tight regulation on host cells. Neutrophil properdin plays a key role in coordinating innate immunity during bacterial infections.
Area of Science:
- Immunology
- Systems Biology
- Computational Biology
Background:
- The complement system is crucial for innate immunity, detecting and eliminating pathogens.
- Dysfunctional complement regulation leads to autoimmune diseases.
- Understanding the balance between complement activation and regulation is vital.
Purpose of the Study:
- To develop a comprehensive quantitative model of the complement system's alternative pathway.
- To analyze complement activation and regulation dynamics on different surfaces.
- To investigate the role of neutrophil-secreted properdin in innate immunity.
Main Methods:
- Developed a quantitative model using ordinary differential equations for the alternative pathway.
- Simulated complement dynamics under physiological conditions.
- Incorporated cellular dimensions of bacteria (E. coli) and host cells (human erythrocytes).
- Included neutrophil-secreted properdin to model crosstalk.
Main Results:
- Demonstrated robust alternative pathway activation on pathogen surfaces (saturation in ~54 minutes).
- Showed minimal complement component occupation on host cells.
- Revealed that complement regulation initiates in the fluid phase, dismantling fluid phase convertases.
- Highlighted properdin's role in initiating and propagating the alternative pathway during bacterial infection.
Conclusions:
- The quantitative model provides insights into the alternative pathway's dynamics.
- Complement exhibits robust activation on pathogens and tight regulation on host cells.
- Neutrophil properdin is integral to coordinating innate immune responses via the alternative pathway.
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