L4- Complement Flashcards
(55 cards)
When does complement get involved in immune defence?
Once APC have sensed antigen
Where is the components of the complement system made?
Liver
What is complement?
Complement (C’) system: a collection of >30 heat labile proteins present in blood and other body fluids
• Augments:
o opsonization and killing of bacteria [in presence or absence of antibodies]
o induction of inflammatory responses that help fight infection
In the absence of infection, C’ proteins circulate in an inactive form are called what?
Zymogen
What happens once complement is activated?
Detection of pathogens or antibody bound to pathogens activates a cascade of proteolysis in which C’ zymogens are activated sequentially, each becoming an active protease which cleaves and activates many molecules of the next zymogen in the pathway – final result is formation of effector C’ components that aid removal of pathogen
Which C’ is responsible for;
Binding to antigen: antibody complexes and pathogen surfaces
C1q
Which C’ is responsible for;
Binding to carbohydrate structures such as mannose or GlcNAc on microbial surfaces
MBL
Ficolins
C1q
Properdin (factor P)
Which C’ is responsible for;
Activating enzymes
C1r C1s C2a Bd D MASP-2
Which C’ is responsible for;
Membrane-binding proteins and opsonins
C4b
C3b
Which C’ is responsible for;
Peptide mediators of inflammation
C5a
C3a
C4a
Which C’ is responsible for;
Membrane-attack proteins
C5b C6 C7 C8 C9
Which C’ is responsible for;
Complement receptors
CR1 CR2 CR3 CR4 CRIg
What are the 3 pathway names of C’ activation?
Lectin pathway
Classical pathway
Alternative pathway
Describe lectin pathway of C’ activation
Lectin pathway is initiated by soluble carbohydrate-‐binding proteins (mannose-‐binding lectin and ficolins) that bind to carbohydrate structures on microbial surfaces
Describe classical pathway of C’ activation
Classical pathway is initiated when C’ component C1 (recognition protein C1q associated with proteases C1r and C1s) recognizes a microbial surface or binds to antibodies on microbial services
Describe alternative pathway of C’ activation
Alternative pathway can be initiated by spontaneous hydrolysis and activation of C’ component C3 , which can then bind to microbial surface
When any pathway interacts with pathogen, a C3 convertase is created which cleaves C’ component C3 to C3a (involved in inflammation) and C3b (the main effector molecule of the C’ system.
T or F?
True
C3a and C5a do what together?
Recruit phagocytic cells to site of infection and promote inflammation
What does C3b do?
Phagocytes with receptors of C3b engulf and destroy the pathogen
(After release from C3a it is bound to the microbial surface)
Completion of the complement cascade ends with the formation of what?
Membrane attack complex (MAC) which disrupts cell membrane and causes cell lysis
Lectin pathway is triggered by any of four different pattern recognition receptors (PRRs) present in blood and extracellular fluids, that recognize carbohydrate on microbial surface. What are they?
- Mannose-‐binding Lectin (MBL)
* Three ficolins: L-‐ficolin, M-‐ficolin, and H-‐ficolin
The production of ______ collection increases in acute phase infection?
Mannose-‐binding lectin (MBL);
Individuals deficient in MBL or MASP-‐2 have more respiratory infections, caused by common extracellular bacteria, during early childhood
Which pathway uses soluble receptors that recognize microbial surfaces to activate the complement cascade
Lectin pathway
Which PRR forms trimeric clusters of carbohydrate-recognition domains and binds with high avidity to its carbohydrates
MBL
High avidity to both mannose and funisex residues