Innate Immunity 2 Flashcards
what is the definition of complement system?
group of soluble proteins that work with innate and adaptive immune systems
what are the 3 functions of the complement systems?
- eliminate pathogens
- eliminate dying cells
- eliminate immune complexes
what is most of the complement system comprised of?
proteases in the blood and other fluids
how many proteases are involved in the complement system?
> 30
what is a protease?
an enzyme that performs proteolysis
how are proteases in the complement system named? 2 ways
have the letter C, followed by a number
some called “factor” followed by a capital letter
how are proteases numbered?
based on when they were discovered
where are most complement proteins produced?
liver
what are the 3 main mechanisms of action of the complement system?
- increasing vascular permeability and chemotaxis (inflammation)
- destroying pathogen cell membranes so they burst
- increasing recognition of pathogens and opsonization
what are the 3 ways that the complement system is activated?
- classical pathway
- alternative pathway
- lectin pathway
what are complement proteins called before they are activated?
pro-proteases
what 2 fragments are produced by proteolytic cleavage of complement proteins?
1 small fragment, 1 large fragment
how is the small fragment named?
identified by letter “a” after C#
what type of cleavage is used to cleave complement proteins?
proteolytic cleavage
how is the large fragment named?
identified by letter “b” after C#
what is the function of the small fragment of cleaved complement protein?
has specific function for clearing out the pathogen
what is the function of the large fragment of cleaved complement protein?
proteolytic activity on a new substrate
what is C3 convertase?
cleaves C3
what are the 2 forms of C3 convertase?
C4b2a and C3bBb
where do the pro-proteases (inactive complement proteins) circulate until they become activated?
in blood
what is the role of initiators in the complement system?
initiate the complement reactions to allow for more complement proteins
what occurs during the complement cascade?
cleavage and activation of a complement reaction sequence
what are the 3 main molecules produced from the complement system?
- opsonins
- Anaphylatoxins
- membrane attack complex
what does the complement system ultimately trigger?
inflammation
what is the role of regulators in the complement system?
inhibits formation of MAC on host cells
what are the 4 common things about the 3 complement pathways?
- all occur on pathogen surfaces
- all activate complement
- all generate C3 convertase
- all promote inflammation, phagocytosis, MAC
what triggers the lectin pathway?
lectins
what are lectins?
soluble proteins that are PRRs which circulate in blood
what are 2 examples of lectins?
- mannose-binding lectin (MBL)
- ficolins
when does the expression of lectins increase?
during infection
where do lectins bind?
carbohydrates on the surface of pathogens
lectins are an example of _____
a PRR
what are the 2 main results of the lectin pathway?
- triggers the signaling cascade on the pathogen surface
- generates C4b2a (C3 convertase)
what are MASPs and their functions?
proteases on the pathogen surface
activated when lectin binds to allow for the cleavage of complementary proteins, cleaves C4 and C2 to make C4b2a
what protein binds to the pathogen surface in the classical pathway?
C1q
is C1q soluble or non-soluble?
soluble
where does C1q bind? (2)
- binds pathogens directly
- binds antibodies that are bound to pathogen surface
when does C1q bind antibodies?
when you have previously been infected with an antigen and are now re-infected
what complement pathway links the adaptive immunity to innate?
classical
what are the steps for C3 cleavage in the classical pathway?
- C1q binds
- signaling cascade on pathogen surface is triggered
- C4b2a is produced
- C3 is cleaved to C3a and C3b
which 2 pathways result in activation of C3 convertase (C4b2a)?
classical and lectin
what is C3a involved in?
enhancing inflammation
what is C3b involved in? (2)
- opsonization
- C5 convertase (C5a and C5b)
when is the alternative pathway activated?
once C3b has been produced by the lectin or classical pathway
what is the alternative pathway and its purpose?
amplifies C3b production and deposits more C3b molecules on the pathogen
what does the alternative pathway require? (2)
- factor B
- protease factor D
what are the 4 steps of the alternative pathway?
- C3b deposited on membrane by lectin/classical pathway
- C3b binds factor B
- factor B is cleaved by plasma protease factor D into Ba and Bb
- forms C3bBb complex –> C3 convertase
- C3bBb can cleave many more C3 molecules
when does C3 undergo spontaneous hydrolysis? and what does it involve?
when there is high concentration of C3
involves factors B and protease factor D
why is C3bBb different from C4b2a?
it is very unstable!! can fall of pathogen surface
what stabilizes C3bBb?
properdin (factor P)
what type of cells secrete properdin/factor P?
neutrophils
how does properdin/factor P stabilize C3bBb?
it binds to some microbial surfaces
what do all 3 complement pathways do?
activates a C3 convertase to C3a and C3b which has many downstream effects
what are 2 results of a complement deficiency?
- extracellular bacteria are more difficult to clear
- complement proteins bind to pathogens in circulation
what are 2 complement proteins involved in inflammation?
- C3a
- C5a
how do C3a and C5a promote inflammation?
- recruit phagocytes
- increase permeability of blood vessels
what causes anaphylactic shock?
large amounts of C3a and C5a causing too much fluid leakage from blood vessels
what do complement receptors connect?
complement receptors connect complement-tagged pathogens to effector cells
what do C3a and C5a receptors on granulocytes do?
stimulate release of PROINFLAMMATORY CYTOKINES and GRANULE COMPONENTS from basophils, eosinophils, neutrophils, mast cells
does the complement system increase or decrease phagocytosis?
increase
which complement protein do phagocytes have receptors for?
C3b
how does C3b affect phagocytosis?
causes opsonization
what are 2 ways that opsonization can occur?
- complement proteins
- antibodies
what does MAC stand for?
membrane-attack complex
what does MAC cause?
a pore in the pathogen surface, leading to cell lysis
which 2 complement proteins are involved in MAC production
C5b and C3b
is C5b directly or indirectly involved in MAC?
DIRECTLY
how is C5b involved in MAC?
binds pathogen surface and recruits other complement proteins to form MAC
is C3b directly or indirectly involved in MAC?
indirectly
how is C3b involved in MAC?
bc it is a C5 convertase, allowing C5b production which therefore allows MAC production
what is the general role of complement-REGULATORY proteins?
prevent complement from being activated under normal/basal conditions
where are complement-regulatory proteins located?
in plasma or cell surfaces
how do complement-regulatory proteins prevent complement activation under normal/basal conditions?
- prevent production C3 convertase
- promote destruction of C3 convertase
what is an example of a result of complement-regulatory protein activity?
inhibited MAC formation by preventing a specific complement protein from binding
why are antibodies not considered PRR?
bc they are v specific
