Complement Flashcards
What is the commonest reason for abnormal complement study result?
Delayed transport to laboratory for processing
Complement is heat labile and degrades quickly
What are the major function so fthe complement pathway?
- cytolysis: creates pores in cell walls
- opsonisation: coating or target cell with complement enhances phagocytosis
- intiate inflammatory response: release of anaphylotoxins
- immue compex clearing: coating with complement results in solubisation, increased circulatory clearance (autoimmune disease often unable to clear–> deposition)
Which are the componenets of the classical complement pathway?
C1q, C1r, C1s, C2, C4, C3
Which are the componenets of the alternate complement pathway?
C3, B, D, Properdin (factor P)
Which are the componenets of the common complement pathway?
C5, C6, C7, C8, C9
What is the C3 tickover component of the alternate pathway?
“Innate” part of the complement system
Aim is to generate C3b which can bind to foreign surfaces
Low level constant conversion of C3–> C3b int he body, if comes into contact with water (eg no surface), is degraded
if comes into contact with a surface not expressing a complement control protein–> labels as foreign, and activates pathway
What is the remainder of the alternate pathway after foreign surface is identified through tickover?
C3b binds to foreign surface
binds factor B and D, C3bBb (alternate pathway C3 convertase) is stabilised by Properidin
converts C3 to C3b further, coats target surface with multiple molecules
C3bBb can bind another C3b and become C3bBbC3b, which is C5 convertase
How is the classical complement pathway triggeredd?
principle effector mechanism of IgG and IgM
acitvation results in classical pathway C3 convertase which generates C3b on the surface targeted by the antibody
once C3b is generated, amplificaiton by alternate pathway occurs
What is the action of C1 in the complement system?
5 proteins (C1q, 2xC1r, 2xC1s)
C1q binds to Fc portion of antibody 9must be bound, not free/circulating)
C1s able to cleave C4 and C2
activating C1q also binds directly to some bacteria and to CRP
Which immuoglobulins are able to bind complement?
IgG and IgM IgG3>1>2>>>4 cia CH2 domain IgM via CH3 domain not IgA, E, D needs >/= 2 IgGs or IgM
How is C4 activated in the classical pathway?
C1s cleaves C4 (C4a and C4b)
C2b (cleaved by C1s) binds to C4b
C4b2b is classical pathway C3 convertase
What is the action of classical pathway C3 convertase?
C4b binds to C3
C2b cleaves it to C3b–> opsonisation and amplification
C3b binds to C4b2a to be C5 convertase
What is the interaction between the classical and alternate pathways?
classical pathway utilises alternate to amplify response
C3b can also bind to Factor B
Converted by D to Bb
stabilised by properdin which generates more C3b
What are the components of the Lectin complement pathway
activation of the pathway by Mannose-Binding Lectin and Ficollins1-3
MBL: structurally and functionally similar to C1q, associates with MASPs1&2 which on activation cleave C4 and C2
Ficollins: bind to various surface structures or microorganisms and altered self proteins, assembles into large mulimeric structures that interact with MASPs1&2
Which componens of the complement cascade are anaphylatoxins? What are their physiological effects?
C5a>C3a»C4a
designed to act locally and mediate inflammation
excessive release can cause anaphlylactic shock
- induce smooth muscle contraction
- increased vascular permeability
- increase expression of adhesion molecules
- activate mast cells
C5a is also a potent chemotactic factor
