Chp 2—Immediate innate immunity Flashcards
complement made by…
liver
zymogen
inactive until cleaved
C subunits held together by…
thioester bond
C subunits are cleaved by..
nucleophiles
may be on pathogen surface, or water
C3b opsonizes via…
complement fixation
C3a function
chemoattractant
inflammation
3 complement pathways in order of action
- alternative
- lectin
- classical
what state is C3 in when it is released from liver?
thioester is not exposed, but slowly and spontaneously becomes exposed
when C3’s thioester is attacked by water…
C3 becomes iC3
driving force of alternative pathway
pathogen surface creates an environment where the rate of catalyzation from C3 to iC3 is higher
iC3 binds to….
causing…
inactive factor B
makes it susceptible to cleavage by factor D
iC3 cleavage results in…
Ba, released
Bb, remains bound to iC3, forming iC3bBb
C3bBb function
alternative convertase which cleaves C3
When does iC3bBb become an alternative convertase?
when it attaches to pathogen surface
RCA / CCP
properin/factor p
factor H
factor I
decay-accelerating factor
membrane cofactor protein
properdin/factor p function
binds to C3bBb on pathogen surfaces and prevents its degradation by proteases
factor I and factor H function
inactivate C3b to give iC3b
decay-accelerating factor function & location
human cells
binds to C3b of alternative C3 convertase, causing its dissociation
membrane cofactor protein function & location
human cells
functions the same as DAF - also makes C3b more susceptible to inactivation by factor I
Kupffer cells
macrophages of the liver
how does C3b opsonize?
macrophages have CR1 which bind to C3b on pathogen surface
CR3 & CR5 function
can also bind iC3b, which has no convertase activity but may be attached to pathogens
complement involved in perforation
C5 - C9
function of C5
cleaved - C5b initiates membrane attack complex
what binds to C5a in plasma?
C6 & C7
binding of C7 to C5a causes…
hydrophobic region of C7 to be exposed, which attaches to pathogen membrane
occurs after C7 attaches to membrane
C8 binds to C5a, and the same thing happens as C7
C8 initiates…
polymerization of C9, forming transmembrane pores
deficiency in any complement involved in MAC increases susceptibility to…
Neisseria
protects human cells from MAC
how?
s proteins, clusterin, factor J, and protectins (CD59)
prevent C9 recruitment
anaphylatoxins
C3a and C5a
functions of C3a and C5a
Act on phagocytes, mast cells, basophils, and endothelial cells to initiate degranulation of histamine, smooth muscle contraction, vasodilation, and increased capillary permeability
Cause neutrophils and monocytes to adhere to blood vessel walls - increase their phagocytic capacity by causing upregulation of CR1 and CR3
released by platelets
prostaglandins, hydrolytic enzymes, growth factors such as PDGF
function of bradykinin
increases vasodilation, bringing more materials of innate immunity to the site
responsible for long covid
bradykinin/kinin system
function of 𝛼2-macroglobulins
contain thioester bonds acting as “bait” - conformational change upon binding of pathogen proteases “wraps up” the protease and inactivates it
function of defensins
disrupt membranes
defensins produced by…
epithelia, neutrophils, Paneth cells
defensins produced by neutrophils are activated by…
salt
biochemical structure/function of defensins
amphipathic
hydrophobic region becomes embedded in membranes, disrupting the bilayer and creating holes in the membrane
2 classes of defensins
𝛼-defensins and β-defensins
what class of defensins are cryptdins?
alpha
plasma protein that opsonizes, but not very specifically
pentraxin
