CMB1003/L20 Complement System Flashcards
Describe the complement system. (3)
Protection in early infections
Major effector system of humoral branch of innate and adaptive immune system
Group of nearly 30 serum and membrane proteins
What is the goal of the complement system? (3)
Inflammation
Phagocytosis
Membrane attack to kill pathogen
Give 3 roles of the complement system.
Opsonisation
Inflammatory response
Activation of B cells
Generation of membrane attack complex (MAC)
Describe the classical pathway of complement activation. (2)
Antibody binds to specific antigen on pathogen surface
Initiated by antigen:antibody complexes
Describe the lectin pathway of complement activation. (2)
Mannose-binding protein binds to pathogen surface
Triggered by some pathogen surfaces
Describe the alternative pathway of complement activation. (2)
Pathogen surface creates local environment conductive to complement activation
Initiated by acute phase proteins that bind glycoproteins or carbohydrates on micro-organisms
What is the nomenclature of components of the classical pathway? (2)
C followed by a number
Products of cleavage reaction have lower case letter added
What is the nomenclature of components of the alternative pathway?
Different upper case letters than C
What is the difference between C5a and C5b?
C5a is smaller
C5b is larger
What is the first component of the classical pathway? (3)
C1
Complex of C1q, C1r & C1s
2 molecules of C1r and C1s bind to each C1q
Describe how IgM molecules trigger the classical pathway. (3)
Pentameric IgM molecules bind to antigens on bacterial surface and adopt staple form
C1q binds to a single IgM molecule
Binding of C1q to immunoglobulin activates C1r which cleaves and activates the serine protease C1s
Describe how IgG molecules activate the classical pathway. (3)
IgG molecules bind to antigens on bacterial surface
C1q binds to at least 2 IgG molecules
Binding of C1q to immunoglobulin activates C1r which cleaves and activates the serine protease C1s
Describe the structure of the C1q molecule.
Six globular heads joined to common stem
Each globular head can bind to one Fc domain on antibody
How many globular heads of C1q must bind to Fc domain for activation of C1q?
2
What does binding of a single IgM or 2 IgG molecules trigger? (3)
Conformational change in C1q
Reveals proteolytic site on C1r
C1r cleaves C1s to generate serine protease enzyme C1s
What is the role of the active C1s in the classical pathway? (4)
C1s cleaves C4 to C4a & C4b
C4b binds covalently to pathogen surface
C2 binds to C4b on antigen/pathogen surface
C2 is cleaved by adjacent C1s leaving C4b2a complex (C3 convertase)
What is the role of C3 convertase?
Cleave large numbers of C3 molecules to C3a & C3b
What is the main effect of the classical pathway? (3)
Lots of C3b on pathogen surface
Opsonisation of pathogens
Phagocytosis of pathogens
What does C3b do? (2)
Acts as an opsonin
With antibody, facilitates recognition by phagocytes
What bond on C3b is exposed after cleavage and why is this useful?
Thioester bond
Allows C3b to bind covalently to pathogen surface
Becomes inactive quickly via hydrolysis if not bound
Describe what occurs after the formation of C4b2a3b in the classical pathway. (5)
C5 binds to C4b2a3b (C5 convertase)
C5 -> C5a & C5b
C5b binds to pathogen surface and binds C6 -> C5bC6
C5bC6 binds C7 -> C5bC6C7
Conformational change - C7 inserts into lipid bilayer of pathogen wall
What is the role of the membrane attack complex (MAC)? (4)
Displaces cell membrane phospholipids
Channel
Disruption of membrane
Cel lysis/death
What is the C3 convertase of the classical pathway?
C4b2a
What is the C5 convertase of the classical pathway?
C4b2a3b
Describe the alternative pathway cascade. (5)
Different C3 convertase
C3 undergoes spontaneous hydrolysis
C3b binds to surface
Factor B binds C3b
Cleaved by factor D -> C3bBb
What stabilises C3 convertase in the alternative pathway?
Factor P/ properdin
What is the C3 convertase in the alternative pathway?
C3bBb
Describe the role of C3bBb in the alternative pathway. (4)
Add another C3b
-> C3b2Bb = C5 convertase
C5 -> C5a & C5b
C5bC6C7C8C9 = MAC
What is the role of the lectin pathway? (2)
Recognise microbial surfaces
Activate complement cascade
What does the lectin pathway use?
Soluble receptors (acute phase proteins)
Describe the cascade of events in the lectin pathway. (4)
Activated MASP-2 associated with MBL or ficolin cleaves C4 to C4a & C4b, which binds to microbial surface
C4b binds C2, which is cleaved by MASP-2 to C2a and C2b forming C4b2a complex
C4b2a (C3 convertase) cleaves C3 to C3a and C3b, which binds microbial surface or convertase itself
One molecule of C4b2a can cleave up to 1000 molecules of C3 to C3b
What is the C3 and C5 convertase of the lectin pathway?
C3 - C4b2a
C5 - C4b2a3b
What is the consequence of C3 deficiency? (2)
Opsonisation, inflammation and cytolysis affected
Life-threatening infections with range of bacteria
What is the consequence of C6-9 deficiency? (2)
Cytolysis affected
May have problems with infection of Neisseria
