innate immunity Flashcards
effector functions of complement
opsonization and phagocytosis
leukocyte migration, chemotaxis, and inflammation
lysis of pathogens
classical complement pathway
initiated by antibody-antigen complexes
requires two IgG or one IgM attached to microbe
initiation component is C1
recognition component is C1qrs
alternative complement pathway
spontaneously activated
low level cleavage of C3 in plasma aka C3 tick-over –> generation of C3b –> C3b associates with microbial surface
lectin pathway
initiated by sugar residues on microbial surfaces that are not on host surfaces
initiation component is mannose binding lectin or ficolin in complex with MASP-1 or MASP-2
CD59
complement regulatory protein
prevents binding of C9 so that MAC cannot form
decay accelerating factor (DAF)
complement regulatory protein
dissociates C3 convertase so that C3 cannot be split into C3a and b
paroxysmal nocturnal hemoglobinuria
caused by deficiency of complement regulatory proteins
intravascular lysis of RBCs by complement
C1 inhibitor
binds activated C1r and C1s, dissociating them from C1q so that classical pathway cannot be activated
deficiency of C1 inhibitor
leads to HAE = hereditary angioneurotic edema (swelling of skin and larynx)
mechanisms by which complement regulatory proteins function
dissociate complement complexes
promote proteolysis of complement components
deficiency in early classical pathway components
immune complex disease (lupus)
deficiency in early lectin pathway components
increased susceptibility to bacterial infection
deficiency in early components of alternative pathway
increased susceptibility to infection with pyogenic bacteria and Neisseria
deficiency in C3 (all pathways)
increased susceptibility to infection with pyogenic bacteria and Neisseria
deficiency in terminal components of complement pathway (C5b-C9)
inability to generate MAC –> increased susceptibility to Neisseria infection
pro-inflammatory cytokines
TNF alpha, IL-1, IL-6
antiviral state cytokines
interferons
what PRR activates inflammasomes
NLRP, subfamily of NLRs
inflammasome then generates IL-1
CD16
activates NK cells to kill virally infected cells by binding IgG that is bound to target cell
how do NK cells kill by ADCC
release perforin into target cell –> pokes holes
release granzyem into target cell –> induces apoptosis
IL-2
activates NK cells to kill tumor cells
IL-12
stimulates NK cells to produce IFN gamma, which activates macrophages
innate lymphoid cells
ILC1, ILC2, and ILC3
important in early responses to viruses, parasitic worms, and bacteria
C3 convertase
cleaves C3 into C3a and C3b
C3a = chemokine
C3b = opsonin
C5 convertase
cleaves C5 into C5a and C5b
C5a = chemokine
C5b = opsonin, forms MAC with C6-9
most potent component of complement system
C5a
complement component that is central to all three pathways
C3
most concentrated complement component in serum
C3
antibody that activates complement best
IgM is most efficient
IgG is second most efficient
why is C3 not a stable molecule
reactive thioester bond allows spontaneous activation of alternative complement pathway
chronic granulomatous disease
deficiency in expression/function of NADPH oxidase leads to inability to generate superoxide –> defect in killing intracellular bacteria –> increased susceptibility to bacterial infection
