Overview of Complement system
The complement system is composed of 30 different soluble proteins and glycoproteins which are mainly produced by hepatocytes, including serum proteins, serosal proteins, and cell membrane receptors. There are more than 20 types of complement proteins in the serum, which circulate normally in the human body in an inactive form (called zymogen or zymogen). Complement activation is triggered by an antibody when it binds to the antigen. It can also be triggered by certain components of innate immunity. Therefore, the complement system plays a role in both innate and acquired immunity.
About Complement Activation Definition
The complement system is the backbone of the innate immune system and a key component of the adaptive immune system. It is activated only during an inflammatory response. After activation, it can enhance the ability of antibodies and phagocytes to remove microorganisms and damaged cells from the organism and promote inflammation. The complement system can be activated by three different pathways: the classical pathway (CP), the alternative pathway (AP) and the lectin pathway (LP). All three pathways converge at the C3 cleavage point, and then generate the membrane attack complex C5b-9, resulting in lysis of the cells (Fig.1).
Fig. 1 Complement activation pathways.1
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Complement Activation Definition in CP
The CP begins with the formation of the antigen-antibody complex. When the antibody (IgM/IgG) binds to the antigen, the Fc fragment of the antibody undergoes a conformational change, thereby exposing the binding site of the C1 protein. Therefore, antibodies activate the complement system only when they bind to an antigen.
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Complement Activation Definition in AP
Unlike CP, AP does not require the antigen-antibody complex for the initiation of the complement activation. AP is initiated by cell surface components that are foreign to the host. These surface molecules include lipopolysaccharide etc. The AP begins with the activation of C3 and requires the participation of factor B and factor D.
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Complement Activation Definition in LP
The LP is initiated when mannose-binding lectin (MBL) binds to mannose residues on glycoproteins or carbohydrates on the surface of microorganisms. The microorganisms that induce the LP are bacteria, including Salmonella, Listeria, and Neisseria strains, some fungi, and certain viruses, such as HIV-1. The lectin recognizes and binds the carbohydrate of the target cell and then activates complements.
Effector Function of Complement Activation
Some of the main functions of the complement system activation are:
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Opsonization to promote phagocytosis
C3b, which binds to immune complexes or coats on the surface of a pathogen, activates phagocytes. These proteins bind to specific receptors on the phagocytic cells to get engulfed.
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Activation of inflammation
Proteolytic complement fragments C5a, C4a and C3a induce acute inflammation by activating mast cells and neutrophils. All three complement proteins bind to mast cells and induce degranulation, and release vasoactive mediators, such as histamine. In addition, they bind to specific complement receptors on cells of the immune system, triggering specific cell functions, inflammation, and secretion of immunoregulatory molecules.
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Killing of microorganisms
The membrane attack complex formed by the C5b-9 component ruptures the surface of microbial cells, thereby killing the cells.
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Immune complex clearance
The complement system removes immune complexes from the circulatory system and deposits them in the spleen and liver. Therefore, it plays an anti-inflammatory role. Complement proteins promote the solubilization of these complexes and their clearance by phagocytes.
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Reference
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Girardi, Guillermina, et al. "Essential role of complement in pregnancy: from implantation to parturition and beyond." Frontiers in immunology 11 (2020): 1681.
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