Innate Immune System Flashcards
May be the most important complement pathway
Lectin
Most common complement protein; continually being spontaneously cleaved to two components: C3a and C3b
C3
C3b binds…
covalently to hydroxyl (-OH) and amino (-NH2) groups on foreign surfaces
What happens if C3b doesn’t find something to bind to in 60 microseconds
neutralized by a water molecule
What happens after C3b binds to a foreign body?
B sees this and will attach to C3b and then protein D will come along to cleave part of protein B to mke C3bBb = active enzyme; saw-like
BbC3b
converts more C3 into C3b; AKA C3 convertase
C3 convertase can also cleave ANOTHER complement protein
- C5 = C5a and C5b
- C5b attaches to bacterial cell and recruits other complement proteins (C6-9)
- together, form a pore (MAC)
- lysis of organism
proteins in our cells that prevent complement from blowing up our own cells
MCP, DAF, CD59
MBL
mannose-binding lectin
- made in the liver
- mannose is a sugar found in complex molecules on many pathogens; mannose in our cells have different patterns so MBL does not bind to them
- MBL in serum binds to mannose-binding lectin associated serine proteases (MASPs)
- directed, not spontaneous
Lectin pathway procedure
- MBL binds target mannose group on an organism
- MASPs bind to MBL
- activated MASP-2 cleaves C4 to C4a and C4b- some C4b covalently binds to microbial surface
- MASP-2 also cleaves C2 into C2a and C2b
- C2a binds to C4b = classical convertase C4b2a
- C4b2a binds C3 and cleaves it into C3a and C3b; C3b binds covalently to microbial surface
- rest of the cascade is like alternative pathway; leads to formation of MACs
Two other important functions of complement
- C3b on a bacterium can be clipped by a serum protein to form iC3b; can no longer contribute to forming MAC but can opsonize
- C3a and C5a act as chemoattractants for professional phagocytes
Three states of Macrophages
- Resting = garbage collectors
- Primed = can become APCs
- Hyperactivated = stop dividing and focus on killing invaders
Professional Phagocytes
Dendritic cells, Neutrophils and Macrophages
Neutrophils
- found in bloodstream
- short-lived (days) bc toxic and can damage tissue
- NOT APCs
- kill the ndie by apoptosis
- produce cytokines (TNF); enhances inflammatory response
How do phagocytic sentinel cells recognize invaders (PAMPs or DAMPs)
- macs and dendritic cells
- PRRs (TLRs = specific)
- some found on outside of cell; some inside (walls of phagosomes to detect PAMPs released from organisms digested in phagolysosome)
PAMPs have _________ characteristics that are unlikely to mutate.
conserved
TLR4 recognizes
LPS found on all gram -
When PRRs on macs and pDC detect a virus, the cells produce these ‘warning proteins’
interferon alpha and beta
= type 1 interferons
NK cells
- innate
- short-lived (1 week) lymphocytes
- like neutrophils, “on call” from the blood; use same exit mechanism
- in tissue, they divide to boost their numbers
- receive cytokine signals (like IFN alpha & beta) or LPS to boost secretion of cytokines like IFN-gamma
- destroy cells through suicide (interaction of Fas with Fas ligand OR injecting granzymes using perforin proteins)
how do NK cells identify their target cells?
- inhibitory (MHC I) = signals the NK NOT to kill
- activating = surface proteins or carbs expressed when cell is stressed (virus) = kill!
interaction between macs and NK cells
- once NK cells and macs bind to LPS, NK cells will produce IFN-gamma which signals macs to make TNF
- TNF makes mac produce IL-12
- TNF makes NK cells release more IFN-gamma to stimulate more macs
- IL-12 makes NK cells express IL-2 for proliferation
- ALSO, iC3b on target organisms can stimulate macs to make more C3, B, D = replenishing key complement proteins
- macs also increase blood vessel permeability to allow more complement to enter site of infection
these 2 are produced by a hyperactivated macrophage
TNF and IL-12
T or F. Innate response is proportional
T!
