Elsevier

Advances in Immunology

Volume 61, 1996, Pages 201-283
Advances in Immunology

Control of the Complement System

https://doi.org/10.1016/S0065-2776(08)60868-8Get rights and content

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

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