18 - The Complement System Flashcards
The complement system provides protection…
a) throughout infection
b) early on in infection
c) during later stages of infection
d) against reccurrent infection
The complement system provides protection…
a) throughout infection
b) early on in infection
c) during later stages of infection
d) against reccurrent infection
The complement system link both innate and adaptive immune responses. It is a major branch of which part of the immune system?
Humoral
The complement system can be described as a…
A series of proteins which make up a highly regulated enzymatic cascade leading to antigen clearance and inflammatory response.
Four main roles of complement proteins are…
- Opsonisation
- Recruitment of phagocytes and inflammatory regulation (fragments)
- Activation of B cells
- Generation of MAC
The complement system may be intiated by three pathways…
- Classical pathway (antibody binds to antigen on pathogen surface)
- Lectin pathway (mannose-binding protein binds to pathogen surface)
- Alternate pathway (spontraneous activation due to pathogen’s presence)
All 3 complement initiation pathways generate…
C3 convertase
C3 convertase leads to (3)…
- Opsonisation
- Inflammatory response
- Production of MAC
Complement system nomenclature
Classical pathway proteins are designated by the letter __
Products of clevage reactions are denoted by the addition of a ________ _________
Alternate pathway compoenets are designated by other ________ __________
Complement system nomenclature
Classical pathway proteins are designated by the letter C
Products of clevage reactions are denoted by the addition of a lower case letter (e.g. a/b)
Alternate pathway compoenets are designated by other captial letters (e.g. B, D)
The addition of the a/b suffix to the protein name indicates small and large components respectively. The exception to this rule is in the case of…
C2, in which the ‘b’ component is infact larger
The classical pathway involves complement proteins…
- C1q, C1r, C1s
- C4
- C2
The alternate pathway involves complement proteins…
- Factor D
- Factor B
- Factor P (properdin)
Both classical and alternate pathways involve the complement protein…
C3
Terminal complement proteins…
C5, C6, C7, C8, C9 - which generate the MAC
Classical pathway
Step 1…
- Antibodies bind to antigens on bacterial surface
- C1q binds to IgM molecule OR to 2+ IgG molecules
- C1q undergoes conformational change revealing C1r proteolytic site
- C1r proteolytic site cleaves C1s from the complex
C1 complex -> C1s
Classical pathway
Step 2…
- Active C1s cleaves C4 forming C4a and C4b
- C4b binds covalently to pathogen surface
- C4b is bound by C2
- C1s cleaves the C2 resulting in C4b2a complex, aka C3 convertase
- C3 convertase cleaves C3 forming C3a and C3b
C3a promotes inflammation
C3b may opsonise pathogen directly or join the C3 convertase complex
The main effect of the classical pathway is the accumulation of…
C3b on the pathogen surface (leading to phagocytosis by cells with complement receptors)
Classical pathway
Step 3 (formation of MAC)…
- C5 binds to C4b2a3b complex (generated by the addition of C3b to C3 convertase complex in the previous step) aka C5 convertase
- C5 is cleaved to form C5a and C5b
- C5b binds to pathogen surface
- C6 binds to C5b forming C5bC6 complex
- C5bC6 complex binds C7
- Conformational change allows insertion of C7 into lipid bilayer of pathogen
- C5bC6C7 binds C8
- C5bC6C7C8 attracts C9, which forms pore in the pathogen membrane
C5bC6C7C8C9 is the complete membrane attack complex (MAC)
How is C3 hydrolysed in the alternative pathway?
C3 hydrolysis is spontaneous (influenced by local environment)
C3bBb is the C3 convertase found in which pathway?
Alternative
(Classical pathway C4b2a)
In the alternative pathway C3 convertase (C3bBb) is stabilised by…
a) Factor B
b) Factor P
c) Factor F
d) Factor E
In the alternative pathway C3 convertase (C3bBb) is stabilised by…
a) Factor B
b) Factor P
c) Factor F
d) Factor E
In the alternative pathway, factor B is cleaved by…
Factor D (forming C3bBb and Ba)
What is the result of adding another C3b to the alternate C3 convertase (C3bBb)?
Formation of C3b2Bb (C5 convertase), which goes on to form the MAC
The lectin pathway differs from the classical pathway in terms of the formation of which complex?
C4b2a (C3 convertase)
Describe the formation of the C3 convertase in the lectin pathway…
- MASP-2 associated with MBL or ficolin cleaves C4
- C4b binds to C2
- MASP-2 cleaves C2
- Result is C4bC2a complex (C3 convertase)
