DISORDERS OF THE COMPLEMENT SYSTEM

DISORDERS OF THE COMPLEMENT SYSTEM - DISORDERS OF THE...

Info iconThis preview shows pages 1–5. Sign up to view the full content.

View Full Document Right Arrow Icon
DISORDERS OF THE COMPLEMENT SYSTEM The complement system is a multi-molecular system composed of more than 20 proteins, synthesized mainly by the liver; seven serum and five membrane regulatory proteins, one serosal regulatory protein and eight cell membrane receptors that bind complement fragments. These proteins are preceded by the letter 'c' and are assigned numbers in order of their discovery. [1]
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Activation The complement system is an interactive system with one reaction leading to another in the form of a cascade, which is initiated by a wide variety of substances [Table - 1] , and has two phases. In the first phase, a series of specific interactions leads to the formation of intrinsic complement proteinases termed C 3 convertase. Both the classical and the alternative pathways, which use different proteins, produce C 3 convertase. The classical pathway has two units; the recognition unit, which consists of a tri- complex of C 1q , two molecules of C 1r and two molecules of C 1s held together by calcium, and an activation unit C 2 , C 3 and C 4 . The sequence starts with binding of two or more C1q recognition units to Fc non-antigen binding part of antibody. This induces a conformational change leading to autoactivation of C 1r that then cleaves C 1s to its active state. This acts like C 1 esterase and cleaves C 2 and C 4 to form C 2a C 4b , which is the C 3 esterase that cleaves C 3 to form C 3b. C 1q can also be activated by myco-plasma, RNA viruses, bacterial endotoxins and cell membranes of some organelles.
Background image of page 2
Viruses, fungi, bacteria, parasites, cobra venom, IgA and polysaccharides can activate the alternate pathway. C 3b binds to Factor B that is cleaved by Factor D to B b . C 3b B b complex then acts as the C 3 convertase and generates more C 3 through an amplification loop. The binding of Factor H to C 3b increases its inactivation by Factor I. Properdin stabilizes C 3b preventing its inactivation by Factors H and I. The second phase involves the cleavage of C 3b that generates multiple biologically important fragments and large potentially cytolytic complexes. Only five proteins (C 5 -C 9 ) are involved in direct killing of cells. C2 a 4 b 3 b complex from the classical pathway or C 3b B b cleaves C 5 . C 5b activates the terminal complement pathway by associating C 6 , C 7 and C 8 to form macromolecular complexes denoted as C 5b-8 . C 9 molecules bind to this complex to form ring like pores, which lead to trans-membrane channels that cause cell lysis. [2]
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Biologic Effects The biologic effects of the complements include promotion of chemotaxis, anaphy-laxis, opsonization and phagocytosis of microorganisms and immune complex clearance from the circulation. [3] The majority of complements are acute phase reactants and their concentration increases in infection, trauma and injury. C 4a , C 3a and C 5a are anaphylatoxins that bind to mast cells and trigger
Background image of page 4
Image of page 5
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 10/07/2010 for the course DBT 446 taught by Professor Dd during the Spring '10 term at Indian Institute of Technology, Guwahati.

Page1 / 21

DISORDERS OF THE COMPLEMENT SYSTEM - DISORDERS OF THE...

This preview shows document pages 1 - 5. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online