LW - the complement system Flashcards
What is the definition of a complement?
A series of plasma proteins which when activated, interact sequentially forming a self-assembling enzymatic cascade generating biologically active molecules mediating a range of end processes.
Describe the classical complement pathway and the trigger factors that initiate each of these pathways.
Triggered by antibody antigen complexes.
Allows C1q to bind to the complex.
This activates C1r and then C1s.
C1s acts on C4 and C2 to split them into C4a, C4b, C2a and C2b.
C2a + C4b = C3 convertase.
This enzyme acts on C3 to form C3a and C3b.
C2a + C4b + C3b = C5 convertase.
The fragments not formed into enzymes remain soluble and can trigger inflammation.
How does C3 and C5 convertase differ between the different subunits?
The lectin and classical pathway have the same subunits.
The alternative pathway has different subunits forming these enzymes.
What is the effector functions of C3a and C5a?
Mediates inflammation.
Recruits phagocytes.
What is the effector function of C3b?
Binds to complement receptors on phagocytes.
Enhances phagocytosis and removal of immune complexes.
What is the effector function of C5b, C6, C7, C8 and C9?
Form membrane attack complexes.
What are the consequences of complement activation?
- Inflammation
- Removal of particulate antigens and immune complexes. This is by phagocytosis by non-specific adherence, opsonisation and immune adherence.
- Cytolysis
What is opsonisation?
The coating of a particle with an antibody and/or complement to enhance the effectiveness of phagocytosis.
What receptors do phagocytic cells express receptors for?
IgG and C3b
What is immune adherence?
Adherence of C3b particles to macrophages bearing C3b receptors. A mechanism for clearance of circulating antigens in the blood stream.
C3b coated particles are bound by C3bR on erythrocytes and subsequently removed from red blood cell by macrophages within the spleen.
How does the membrane attack complex function?
Forms pores in the surface of pathogens.
This allows for an influx of water and therefore osmotic lysis.
What are the 3 ways that the complement cascade is controlled?
- C1 inhibitor - dissociated r and s.
- Normal cells have membrane proteins that breakdown C3 convertase. This protects normal cells.
- CD59 expressed widely on membranes and prevents the formation of the MAC on normal cells.
How does chemotaxis relate to the complement?
Chemotaxis is important to localise the inflammation. This attracts C3a and C5a to the injured area.
Define chemotaxis.
Migration of a leukocyte along a chemotactic gradient of increasing concentration of chemoattractant.
