Complement System Overview

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Complement System Biology

The complement system is one of the major mechanisms by which pathogen recognition is converted into an effective host defense against initial infection. Complement is a system of plasma proteins that can be activated directly by pathogens or indirectly by pathogen-bound antibody, leading to a cascade of reactions that occurs on the surface of pathogens and generates active components with various effector functions.

There are three pathways of complement activation: the classical pathway, which is triggered directly by pathogen or indirectly by antibody binding to the pathogen surface; the MB-lectin pathway; and the alternative pathway, which also provides an amplification loop for the other two pathways.

All three pathways can be initiated independently of antibody as part of innate immunity. The early events in all pathways consist of a sequence of cleavage reactions in which the larger cleavage product binds covalently to the pathogen surface and contributes to the activation of the next component.

The pathways converge with the formation of a C3 convertase enzyme, which cleaves C3 to produce the active complement component C3b. The binding of large numbers of C3b molecules to the pathogen is the central event in complement activation. Bound complement components, especially bound C3b and its inactive fragments, are recognized by specific complement receptors on phagocytic cells, which engulf pathogens opsonized by C3b and its inactive fragments.

The small cleavage fragments of C3, C4, and especially C5, recruit phagocytes to sites of infection and activate them by binding to specific trimeric G protein-coupled receptors. Together, these activities promote the uptake and destruction of pathogens by phagocytes. The molecules of C3b that bind the C3 convertase itself initiate the late events, binding C5 to make it susceptible to cleavage by C2b or Bb.

The larger C5b fragment triggers the assembly of a membrane attack complex/MAC, which can result in the lysis of certain pathogens. The activity of complement components is modulated by a system of regulatory proteins that prevent tissue damage as a result of inadvertent binding of activated complement components to host cells or spontaneous activation of complement components in plasma.

Pathways of complement system activation

Complement System Overview References

1. Janeway Jr C A, et al. (2001). The complement system and innate immunity.
2. Ruddy S, et al. (1972). The complement system of man. New England Journal of Medicine, 287(11), 545-549.

Complement System
Complement System Overview
What is Complement System
How Does Complement System Work
Complement Protein Fragment Nomenclature
Complement System Component / Protein Regulator and Receptor
Complement Component / Protein of Complement System
Complement Regulator of Complement System: RCA/CCP family
Complement Regulator of Complement System: Others
Complement Receptors of Complement System
Complement Genetic Feature
Regulator of complement activation / RCA Gene Cluster
Complement MAC Gene Cluster
Complement MHC Class III Gene Cluster
Complement Activation Pathways
Complement Activation Definition
Complement Activation Classical Pathway
Complement Activation Alternative Pathway
Complement Activation Lectin Pathway
Serine Proteases of Complement Activation Pathway
Complement System Role
Complement System and Direct Interactions
Complement System Function in Immune System
Complement-Dependent Cytotoxicity/CDC
Therapeutic Target of Complement System
Complement System and Toll-like Receptors / TLRs
Complement System and Coagulation
Complement Cascade and Inhibitors
Complement Evasion of Pathogens
Complement System and Antimicrobial Peptides/AMPs
Complement System and Diseases
Complement System and Cancer
Complement System and Rheumatic Diseases
Complement Receptor 1 / CR1 and Alzheimer's Disease / AD
Complement System and Autoimmune Diseases
Complement System and Age-Related Macular Degeneration/AMD
Complement System and Schizophrenia
Complement System Deficiency Diseases
Classical Pathway Deficiency
Alternative Pathway Deficiency
Complement Receptor Deficiency
Mannose-Binding Lectin / MBL Pathway Deficiency
Membrane Attack Complex/MAC Deficiency
Total Complement Activity / CH50 / CH100
Complement System Structure
Complement Membrane Attack Complex/MAC
Complement Component / Protein Structure
Complement Regulator Structure
Complement Receptor Structure
Collectins and Ficolins: Humoral Lectins of the Innate Immune System
Complement System Effector Functions
Complement Mediated Opsonization
Complement Mediated Cell Lysis
Complement Mediated Phagocytosis
Complement Mediated Inflammation
Complement Mediated Chemotaxis
Complement Mediated Antibody Formation
Anti-Complement Antibody Products