Complement System Flashcards
What is the complement cascade?
Enzymatic response to infection
What is purpose of pathways?
- Opsonises pathogens for phagocytosis by macrophages and neutrophils
- Produce MAC
- Produce anaphylatoxins
- Attract neutrophils to site of infection
What are the 3 main pathways of complement activation?
- Classical pathway
- Lectin or mannose-binding pathway
- Alternative pathway
What is the classical pathway activated by? What does it require?
Antigen-antibody complexes. Requires activation of adaptive immune system first
Activated when complement factor C1 binds to antibody-antigen complexes (generated by adaptive immune system)
What are most of the complement factors?
Serine proteases - similar to trypsin (digestive enzyme) but much higher specificity
How is the next factor activated in the classical pathway?
Limited proteolysis (one protein one cut)
Which by products of the CP are anaphylatoxins?
C3a, C4a and C5a
Which product of the
CP plays a role in opsonisation?
C3b
What are the steps of the CP?
- C1 cleaves C2 into C2a and C2b
- C1 also cleaves C4 into C4a and C4b
- C2a and C4b form a complex (C2a/C4b) which cleaves C3 into C3a and C3b
- C3b joins C2a/C4b complex forming a C2a/C4b/C3b complex which cleaves C5 into C5a and C5b
- C5b finally forms complex with C6, C7, C8 and C9 to produce MAC
What is function of MAC?
Membrane Attack Complex - perforates cell membrane of pathogens / virus-infected host cells
What is the lectin / mannose-binding pathway activated by?
Direct contact with pathogen - mannose binding lectin binds to mannose on pathogen surfaces
What is mannose-binding pathway based on?
Particular sugar (mannose) is found on cell membrane of many pathogens, but not on host cells
What protein binds mannose on pathogens?
Mannose Binding Lectin (MBL)
What proteases do MBL bind?
MASP 1 and 2
MBL and MASP complex cleaves what factors?
C2 and C4, forming C2a and C2b and C4a and C4b
What pathogens express mannose and bind MBL to activate the lectin pathway?
- Yeast –> Candida albicans
- Viruses –> HIV and influenza
- Bacteria –> Salmonella and Streptococci
- Parasites –> Leishmania
What parts of the lectin pathway and classical pathway are identical?
C3-C9
What is the alternative pathway activated by?
Direct contact with pathogen
Alternative pathway involves auto-activation of C3 at a very low rate. How does this come about?
C3 is very unstable so can activate itself, forming C3b
What does auto-activated C3b bind to?
Some C3b binds to pathogens
Some binds to factor B
Some binds to properdin
This rapidly activates more C3 and C5
What part of alternative pathway are identical to lectin and classical pathway?
C6-C9
What are anaphylatoxins?
By products - C3a, C4a and C5a (C3b, C4b and C5b play main role)
What is function of anaphylatoxins?
- Trigger degranulation of endothelial cells, mast cells and phagocytes
- Cause smooth muscle contraction and enhance vascular permeability
- Attract neutrophils
What do C3a and C5a also act as?
Chemoattractants
What is purpose of chemoattractants?
Attract and activate neutrophils
What do mast cells release?
Histamine
What is benefit of smooth muscular contraction and enhanced vascular permeability?
Easier for neutrophils and NK cells to infiltrate infected tissue
What factor is involved in opsonisation?
C3b
What is opsonisation?
Pathogens are labelled to increase recognition by phagocytes - renders bacteria more susceptible to phagocytosis
C3b is cleaved on bacterial surface to what? How does this assist phagocytosis?
iC3b
Macrophage membrane contains receptors for iC3b as iC3b is recognised
What is name of complex/enzyme that C2a and C4b form?
C3 convertase
What forms MAC?
C5b forms complex with C6, C7, C8 and C9 to form MAC
