Innate immunity: Complement Flashcards
What does complement system refer to
Group of soluble proteins that cooperate with both innate and adaptive immune systems =
Eliminate pathogens, during cells and immune complexes from body
What is a protease
Most make up complement system
>30 in blood and other fluids
Enzyme that performs proteolysis = can break down proteins
Naming proteases
Called C followed by number
Some called factor followed by cap letter
Most numbered based on when discovered
What are complement proteins produced by
Mostly produced by liver
What do complement proteins do
Set off A chain reaction that helps clear pathogens = cascade/chain reaction of events
Describe 3 key mechanisms of action of complement system
Increasing vascular permeability and chemo taxis = promote inflammation, vasodilate= more cells to site of infection
Destroy pathogen cells membranes = Poke holes
Increasing reognxiiotn of pathogens and facilitating phagocytosis = opsonization
Define opsonizaton
Coating of surface of Pathogen by antibody and/or complement that makes it more easily ingested by phagocytes, make tasty, enhance phagocytosis
Define phagocytosis
Receptor of opsonins on Phagocytes
Internalization of a particular matter by cells by a process of engulfment, cell membrane surrounds material, eventually forming intracellular vesicle = phagosome = contains ingested material
How does complement get activated
Classical, alternative or lectin pathway
Initially pro proteases then act as cascade = proteolytic cleavage generating 2 fragments
Describe products of proteolytic cleavage of complement
One small = a, with specific function
One large = b, with proteolytic activities on new substrate
Name the 2 c3 convertases
C4b2a
C3bBb
Both cleave c3 into c3a and c3b
Describe functional categories of complement proteins - gen
Group of pro proteases = inactive, circulate in blood until activated= cleaved
Proteins are inactive untill cleaved by proteases
Need initiators first
Describe functional categories of complement proteins - whole cascade generally
Initiators = initiate respective complement reactions
Convertase activators and some enzymatic mediators = cleave and activate next member of a complement reaction sequence = cleave other complement proteins, immune cells have receptors for these complement proteins
= 3 outcomes = opsonins, anaphylatoxins and membrane attack complex
Regulators = inhibit formation of Mac on host cells —> always regulated
What’s essential to know about complement activation
3 pathways can activate compel T
All 3 generate c3 convertase = cleaves c3–> c3a + c3b
3 main outcomes = downstream effects
What is lectin pathway triggered by
Triggered by soluble proteins known as lectins
= prrs that circulate in blood, not membrane bound
Binds polysaccharide antigen
Name lectins
Mannose binding lectin
Ficolins
What increases during infection
Expression of lectins
Describe lectin pathway prrs
Bind surface of pathogens
Triggers signalling cascade on pathogen surface = c3 convertase generated (c4b2a) = cleaves c3
Describe lectin pathway - generally whole process
Once binds pamp = change conformation of MASPs (proteases)= starts cleaving complement proteins = triggers cascade = c4b2a
Describe how classical pathway activated
C1q binds pathogen surface
Can bind pathogen directly
Can bind antibodies that are bound to pathogen surface
What does classical pathway do
Connect adaptive to innate
Antibodies produced by B cells - can bind antibodies
Innate immune component helps mediate humoral response
What happens when c1q binds
Triggers signalling cascade on pathogen surface
Proteases = c1r2r2 switches on and cleaves and makes c4b2a
What do all pathways converge on
C3
Classical and lectin = make c4b2a
Alternative = makes c3bBb
What does c3 convertase do
Cleaves c3–> c3a and c3b
