Complement System Flashcards
What type of response is the complement system?
Innate
What is the over all response of the complement system?
Recognise pathogens, trigger response
Directly lyse, opsonise (taken up and digested), chemoattractant (recruitment of other cells), degranulation of mast cells
How can the level of the components of the complement system be measured in animals?
In serum of all animals
How does the complement system use zymogen like proteins?
Recruitment and activation of zymogen like proteins
Zymogen proteins split in two, one is retained, other acts as enzyme/chemoattractant
What are the modes of action of the different complement system responses?
Direct inhibitors/blockade
Decay accelerator factors
On WBC surfaces speeds up decay of convertases
CD59 inhibits formtation of the MAC on host cell surfaces?
What is MAC?
Membrane attack complex
What are the three different types of complement pathways?
Classical
Alternative
Lectin
What do all complement systems target and effect?
Effect- phagocytosis, cell lysis, WBC recruitment and activation
Target- Bacteria, viruses, parasites, fungi
What is the activating signal and difference of all three complement pathways?
Classic activation- antibody antigen complex
Classic difference- takes longer as needs Ab
Alternative activation- C3 binds to pathogen carbohydrates or protein
Alternative difference- binds directly to pathogen surface
MB-Lectin activation- host mannose binding lectins binding to pathogen mannose
MB-Lectin difference- binds surface via soluble protein
Describe the classical pathway (clue 1, 4, 2, 3, 5)
Antigen and antibody activates C1 Activated C1 cleaves C4- C4b and C4a C2 binds to C4- C4b2 Active C1 cleaves C4b2- C4b2b and C2a C4b2b cleaves C3- C3b and C3a C5 binds to C3b- C3b5 C4b2b cleaves C3b5- C3b5b + C5a
Describe the alternative pathway (clue C3- B or H)
C3 spontaneously breaks down- C3b and C3a
C3b binds to cell surface
If normal cell factor H causes the C3b to inactivate
If not normal the surface is activating and causes B to bind- C3bB
D cleaves C3bB- C3bBb and Ba
P binds producing C3bBbP
Describe the MB-Lectin pathway (clue MASP-2, 4, 2, 3)
Bacterial surface binds to host mannose binding lectin Mannose binding lectin activates MASP-2 MASP-2 cleaves C4- C4b and C4a C4b binds to C2- C4b2 MASP-2 cleaves C4b2- C4b2b + C2a C4b2b cleaves C3- C3b and C3a
Where is C3 made and by what cells?
Made by macrophages in the liver
What happens to C3 naturally and what follows?
C3 naturally breaks down to C3a and C3b
C3a acts as an anaphylotoxin or chemoattractant
C3b can bind to microbe surfaces by carbohydrates
C3b can bind to factor H on host cells removing from circulation
What is the main similarity between all complement pathways?
All three produce C3 Convertase
MB-Lectin and classical- C4b2b= C3 convertase
Alternative- C3bBb= C3 convertase
How does C3 convertase mediate the actions of the complement system?
C3a, C4a, C5a- peptide mediators of inflammation and phagocyte recruitment
C3b- binds to complement receptors on phagocytes, opsonisation of pathogens, removal of immune complexes
C3b and terminal components (C5b, C6, C7, C8, C9)- membrane attack complex
Which components of the complement system are anaphylatoxins and what do they do?
C3a, C4a, C5a
Change smooth muscle
Increase vasodilation
Activated mast cells of neutrophils
Increases fluid in the tissue and speeds up lymph flow
What is the MAC and what is it composed of?
A central effector mechanism, and an endpoint of all three activation pathways
Composed of C5b, C6, C7, C8 and multiple copies of C9
Describe the mechanism of the membrane attack complex
Cleavage of C5- C5a and b
C5b binds to C6- C5bC6
Binds to C7- C5bC6C7
C5bC6C67 allows C7 to insert onto phospholipid bilayer as hydrophobic site is exposed on the C7 protein once in a complex
Surface complex bound by C8 beta, C8 alpha gamma inserts into the cell membrane
This causes 10-16 copies of C9 to polymerise on the cell surface- think Mario pipes
What does the MAC do?
Opens the bacterial cell Loss of cellular components Homoestasis inhibited Disrupts protein gradient Allows host lysosome penetration
Why is canine C3 deficiency a problem?
Homozygote dogs have no serum C3
Have trouble in making antibodies against certain pathogens
Increase pyometra, pneumonia, sepsis
