Complement was discovered in the 1890s by _____________
Complement proteins are produced mainly where?
in the liver
Where are complement proteins found in the absence of infection?
circulating in plasma
There are how many pathways of complement activation?
What is a zymogen?
inactive enzyme precursor that must be cleaved to be activated
What initiates the lectin pathway of the complement system?
soluble carbohydrate-binding proteins - mannose-binding lectin and the ficolins - that bind to particular carbohydrate structures on microbial surfaces
What initiates the classical pathway of the complement system?
C1 recognizes a microbial surface directly or binds to antibodies already bound to a pathogen
How is the alternative pathway of the complement system initiated?
spontaneous hydrolysis and activation of the complement component C3, which then can bind directly to microbial surfaces
What is the main effector molecule of the complement system?
Cleavage of ___ is a critical step in complement activation and leads directly or indirectly to all the effector activities of the complement system/
What does C3b bind to?
-binds covalently to the microbial surface and acts as an opsonin
-binds to C3 convertases (classical and lectin pathways), forming C5 convertase
In the complement system where cleaved proteins have fragments a and b, which is larger?
b is larger (except C2a)
What is the structural basis for C3b's ability to bind covalently with a microbe?
cleavage of C3 to C3b reveals a hidden thioester bond that reacts with a hydroxyl or amino groups on the nearby microbial surface
What occurs if C3b does not quickly bind to a microbe?
it is rapidly degraded
What are the four PRRs that may trigger the lectin pathway?
What is MBL?
mannose-binding lectin, a PRR that may trigger the lectin pathway
Activated MASP-2 cleaves what complement components?
C2 and C4
What activates MASP-2?
binding of MBL to microbe
What is the C3 convertase of the lectin pathway?
How is C4b2a formed?
MASP-2 cleaves C4, releasing C4a.C4b binds to the microbial surface and binds C2. C2 is cleaved by MASP-2, leaving C2a bound to C4b.
What is the function of C3 convertase?
cleaves C3, producing C3b (major effector) and C3a (induces inflammation)
What proteins make up the group known as collectins?
MBL and ficolins
What are the compenents of the C1 complex?
C1q (pathogen sensor), C1s and C1r (serine proteases)
Classical C3 convertase is made up of what complement components?
Which class of antibodies is most efficient at binding C1q?
Which complement activation pathway is part of the adaptive immune system?
classical (responds to antibodies)
What are the components of the alternative pathway C3 convertase?
Which complement pathway acts as an amplification loop for C3?
What protease cleaves factor B?
What two ways may the alternative pathway be activated?
-action of lectin or classical pathway
-spontaneous hydrolysis (tickover)
Describe the tickover activation of the alternative pathway.
Spontaneous hydrolysis of C3 results in C3(H2O), which can bind to factor B, which is cleaved by factor D
Alternative pathway C3 convertases are stabilized by the plasma protein _________
properdin (factor P)
Properdin is made by ____________
What is the function of complement regulatory proteins?
protect healthy host cells from inappropriate complement activation.
What are some examples of complement regulatory proteins?
-CD55/DAF (decay-accelerating factor)
-CD46/MCP (membrane cofactor of proteolysis)
What are the compenents of the C5 convertase?
What is the function of complement receptors on phagocytes?
recognize pathogens opsonized with complement components (especially C3b) for uptake and degradation
What small complement-cleavage products induce local inflammatory responses?
Which complement components contribute to forming the membrane-attack complex?
"PAMP" = _________________
pathogen associated molecular pattern
What are the two types of parasites?
protozoa and helminths (worms)
What is the difference between endotoxin and exotoxin?
Exotoxins are released by bacteria and cause damage...endotoxins are constituents of the bacteria itself and cause damage by inducing the release of cytokines
What are Paneth cells?
specialized epithelial cells that secrete lysozyme and phosphilipase A
What are the three classes of antimicrobial peptides in mammals?
defensins, cathelicidins, and histatins
What are defensins?
What is MASP-2?
MBL-associated serine protease - binds to MBL (and ficolins) and is activated when MBL/ficolin binds to a pathogen. MASP-2 cleaves C4 and C2
What is the major difference between the lectin and classical complement pathways?
pathogen recognition: lectin pathway recognizes carbohydrates on pathogen surface, classical pathway recognized PAMPs as well as antibodies
What subunit is the "pathogen-sensor" of the C1 complex?
What subunit of the C1complex acts as a serine protease?
What does C1s cleave?
C2 and C4
C4b2a is the C3 convertase of what complement pathways?
lectin and classical
The main effect of complement activation is to deposit large quantities of ______ on the surface of the infecting pathogen.
What is the C5 convertase of the classical and lectin pathways?
What is the C5 convertase of the alternative pathway?
What is the function of C5b?
initiation of the membrane-attack complex by binding to C6, C7,and C8
Which complement pathways may be initiated independently of antibody?
all three (lectin, classical, and alternative)