Control of the Complement System
Section snippets
Overview of Complement Regulation
More than 600 million years ago primitive components of the alternative pathway of complement likely formed the first humoral immune system (1., 2., 3.). Subsequent evolution of an adaptive immune response drove the specialization of a second arm of the complement system, the classical pathway, to connect antibody-mediated events to complement-dependent effector mechanisms. A complement system similar to that in mammals has been identified in reptiles, birds, amphibians, and fish. The
OVERVIEW OF C3/C5 CONVERTASE CONTROL
During the amplification process, C3 convertases cleave C3 to C3b. The goal is to deposit large amounts of clustered C3b on the target. Activities of the C3 convertases are dependent on the association of two components, C4b with C2a in the classical pathway convertase and C3b with Bb in the alternative pathway convertase. For the classical pathway, antibody selects the target and the convertase forms predominantly on the complex. The alternative pathway, however, has no such requirement for
Structure/Genetics/Biosynthesis
S protein is present in human plasma at 0.25–0.45 mg/ml and is also
Structure/Genetics/Biosynthesis
CD59 is a single-chain glycoprotein which, like DAF, is GPI-anchored (366). The gene
Control of Anaphylatoxins
During activation of the complement system, peptides of 74–77 amino acids are released by the splitting of a single Arg–X bond at the amino terminus of the α chains of C3, C4, and C5 (420). Although the anaphylatoxins (C3a, C4a, and C5a) are similar structurally, they differ vastly in their relative potencies (421., 422., 423.). C5a is by far the most powerful anaphylatoxin followed by C3a and remotely by C4a. Additionally, C5a is a potent chemotactic factor.
The spasmogenic activities of the
Summary and Conclusions
The complement system has developed a remarkably simple but elegant manner of regulating itself. It has faced and successfully dealt with how to facilitate activation on a microbe while preventing the same on host tissue. It solved this problem primarily by creating a series of secreted and membrane-regulatory proteins that prevent two highly undesirable events: activation in the fluid phase (no target) and on host tissue (inappropriate target). Also, if not checked, even on an appropriate
References (425)
The classical complement pathway
Activation and regulation of the first complement component
Adv. Immunol.
(1985)- et al.
CI: Molecular interactions with activating systems
Immunol. Today
(1991) C1 inhibitor and hereditary angioneurotic edema
Annu. Rev. Immunol.
(1988)- et al.
Clq, the collagen-like subcomponent of the first component of complement C1, is a membrane protein of guinea pig macrophages
Eur. J. Immunol.
(1993) - et al.
Structure-function relationships of the complement components
Immunol. Today
(1989) - et al.
Complement system proteins which interact with C3b or C4b
Immunol. Today
(1986) - et al.
Solution structure of the fifth repeat of factor H: A second example of the complement control protein module
Biochemistry
(1992) - et al.
Disulfide bonds are localized within the short consensus repeat units of complement regulatory proteins: C4b-binding protein
Biochemistry
(1989) - et al.
Isolation, primary structure, and evolution of the third component of chicken complement and evidence for a new member of the alpha2-macroglobulin family
J. Immunol.
(1995) - et al.
The organization of the human complement factor I gene (IF): A member of the serine protease gene family
Genomics
(1994)
Ultrastructures and interactions of complement factors H and I
J. Immunol.
In vitro biosynthesis of complement factor I by human endothelial cells
Eur. J. Immunol.
Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines
Proc. Natl. Acad. Sci. USA
Human trophoblast-specific surface antigens identified using monoclonal antibodies
Am. J. Reprod. Immunol.
Characterization of three monoclonal antibodies to membrane cofactor protein (MCP) of the complement system and quantitation of MCP by radioassay
Clin. Exp. Immunol.
Membrane Cofactor Protein (MCP; CD46) is a keratinocyte receptor for the M protein of group A streptococcus
Proc. Natl. Acad. Sci. USA
Using membrane-bound complement regulatory proteins to inhibit rejection
Xeno
Polymorphic expression of CD46 protein isoforms due to tissue-specific RNA splicing
Mol. Immunol.
Effects of O-linked glycosylation on the cell surface expression and stability of decay-accelerating factor, a glycophospholipidanchored membrane protein
J. Biol. Chem.
Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs)
Genomics
HuLy-m5, an antigen sharing epitopes with envelope gp70 molecules of primate retroviruses, and a structural relationship with complement regulatory molecules
Soluble forms of membrane cofactor protein (CD46, MCP) are present in plasma, tears, and seminal fluid in normal subjects
Clin. Exp. Immunol.
Complement regulatory proteins in early human fetal life: CD59, membrane cofactor protein (MCP) and decay-accelerating factor (DAF) are differentially expressed in the developing liver
Immunology
Expression of complement-regulatory proteins in normal and UW-preserved human liver
Gastroenterology
Membrane cofactor protein of complement is present on human fibroblast, epithelial and endothelial cells
J. Clin. Invest.
An evolutionary view of the complement system
Behring Inst. Mitt.
Immunol. Today
Evolution of the complement system
The phylogeny and evolution of the complement system
Immunol. Today
Separation of self from non-self in the complement system
Paroxysmal nocturnal hemoglobinuria
Curr. Top. Microbiol. Immunol.
Reaction mechanism of the alternative pathway of complement fixation
Lancet i
Human inhibitor of the first component of complement, C1: Characterization of cDNA clones and localization of the gene to chromosome II
Proc. Natl. Acad. Sci. USA
Human C1 inhibitor: Primary structure, cDNA cloning, and chromosomal localization
Biochemistry
Complete nucleotide sequence of the gene for human C1 inhibitor with an unusually high density of Alu elements
Eur. J. Biochem.
Two-domain structure of the native and reactive centre cleaved forms of C1 inhibitor of human complement by neutron scattering
J. Mol. Biol.
Quantitation of Clr-Cls-Cl inactivator complexes by electroimmunoassay
Acta Pathol. Microbiol. Scand. Sec. C
Activation of the early components of the classical complement pathway under physiologic conditions
J. Immunol.
C1 Inhibitor
Methods Enzymol.
C1 inhibitor deficiency: Molecular and immunologic basis of hereditary and acquired angioedema
Lab. Invest.
The regulators of complement activation (RCA) gene cluster
Adv. Immunol.
Three-dimensional structure of a complement control protein module in solution
J. Mol. Biol.
Phylogeny of regulatory proteins of the complement system. Isolation of a C4b/C3b inhibitor and a cofactor from sand bass plasma
J. Immunol.
Characterization of Xenopus laevis complement factor I structure-conservation of modular structure except for an unusual insert not present in human factor I
Mol. Immunol.
Purification of a lamprey complement protein homologous to the third component of the mammalian complement system
J. Immunol.
Deficiency of C3 Inactivator in man
J. Immunol.
The alternative pathway of complement activation. The role of C3 and its inactivator (KAF)
Immunology
Hereditary complement factor I deficiency
Q. J. Med.
Human complement factor I: Analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4
J. Biol. Chem.
Characterization of the primary amino acid sequence of human complement control protein Factor I from an analysis of cDNA clones
Biochem. J.
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