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The Interplay of Complement Proteins C1q and Factor H

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posted on 2016-01-18, 11:11 authored by Hanan Alrashidi
The complement system in human blood represents a major component of innate immunity. The role of the complement system is to recognise foreign materials coming into contact with the blood, including microorganisms, synthetic particles, or damaged and altered self-components, such as apoptotic and necrotic cells. Complement can be activated via three main pathways: the classical, alternative and lectin pathways. The classical pathway activation is achieved through the binding of the protein C1q to the targets. Factor H is well-known as an inhibitor of the alternative pathway, but as it can bind to many of the same ligands as C1q, it might compete with C1q and, therefore, be involved in the classical pathway control. Different target molecules which activate the classical pathway show variable binding of both of these complement proteins. This thesis explored the binding of C1q and FH to a range of target ligands using the ELISA technique. Previous research has shown that FH can compete directly with C1q binding and inhibit classical pathway activation. Manipulating the relative quantities of C1q and FH in human serum has been shown to influence the extent of classical pathway activation. This role of FH is distinct from its role as a regulator for the alternative pathway. This study measured the FH:C1q molar ratios in human plasmas for the first time, and the results showed a wide range of ratios (1.25:1 to 84:1) as well as widely varying concentrations of C1q and Factor H between individuals. This variation in the molar ratio appeared not only between individuals, but also in single individuals in a longitudinal study. Thus, FH could play an important role in controlling inflammation and have significant involvement in inflammatory diseases.

History

Supervisor(s)

Schwaeble, Wilhelm; Sim, Robert

Date of award

2016-01-04

Author affiliation

Department of Infection, Immunity and Inflammation

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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