Flashcards in Chapter Two Deck (114)
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1
Jules Bordet
nobel prize for his discoveries relating to immunity, 1919
2
definition of complement system
enhances/ complements pathogen destruction by other immune mechanisms
3
how many proteins are made in complement system
over 30
4
where are complement proteins made
in liver
5
proteins in complement system are what type of enzymes
proteolytic enzymes
serine proteases
6
zymogens
complement proteolytic enxymes produced in liver and that are circulating in a healthy individual
7
what triggers the activation of the complement system
infection
8
complement consists of what when activated
protein cleaves and activates next complement protein in the pathway
9
complement activation is similar to
the domino effect
10
what are the three pathways to complement activation
alternative
lectin
classical
11
which complement activation is first to act
alternative
12
which complement activation is last to act
classical
13
what starts alternative pathway
pathogen surface creates local environment conducive to complement activation
14
what starts lectin pathways
mannose- binding lectin binds to pathogen surface
15
what starts classical pathway
c-reactive protein or antibody binds to specific antigen on pathogen surface
16
what pathway is first to respond of immediate innate immune system once barrier has been breached
alternative
17
what is the most important protein in alternative pathway
complement component 3
C3
18
what type of bond in buried in the inactive serine protease
thioester bond
19
a confirmation change of C3 can cause what to thioester bond
can be hydrolyzed
20
when thioester bond is hydrolyzed what happens
new conformational change known as iC3
21
what can now bind to iC3
Factor B
22
what does Factor B do to iC3
allow factor D to attach
23
Factor D does what to Factor B
Factor B cleaves into Bb and Ba
24
what part of factor B stays attached to iC3
Bb, turning into iC3Bb
25
what can iC3Bb do now
cleave C3 molecules into C3a and C3b
26
when C3 molecules are cleaved by iC3Bb what is now exposed
thioester bond, susceptible to nucleophilic attack
27
thioester bond can now attach to what after being cleaved
amino and hydroxyl group of pathogen surface if near it, or attacked by H2O creating inactive soluble C3b
28
what convertase cleaves C3 to C3a and b
C3 convertase
29
complement fixation
when microbe has C3b covalently bound to its surface it is tagged for destruction
30
when C3B is on pathogen surface what can attach to it
Factor B
31
What attaches to Factor B on C3b
Factor D causing cleavage of Factor B
32
what complex is created after Factor D cleaves Factor B on C3b
C3bBb complex
33
C3bBb is also known as
alternative C3 convertase
34
alternative C3 convertse works by
cleaving C3 into a and b exposing thioester bond but since near pathogen surface C3bBb is then attached to surface
35
what is Properdin (factor P) suppose to do
plasma protein that is used to stabilize the C3bBb convertase
36
what is a positive regulator
factor P, create more C3bBb convertase
37
about Factor H
region that binds to sialic residues on eukaryotic host cells
contains region that displaces Bb from the C3bBb convertase complex
cofactor with protease factor I
38
what is involved in negative feedback regulation
Factor H and I
DAF
MCP
39
how does Factor H work
binds to C3b on pathogen surface, cofactor I helps cleave to form iC3b
40
what negative regulation is used for C3bBb
DAF, decay accelerating factor
41
how does DAF work
binds to C3bBb , displaces Bb from convertase rendering it inactive
42
what is another negative regulation used for C3bBb
MCP, membrane cofactor protein
43
how does MCP work
MCP binds to C3bBb kicking off Bb and then cofactor I cleaves molecule and leaves it to iC3b
44
since pathway alternative is not activated by a specific response to a pathogen, there are
host cell regulators of complement activation (RCA proteins) necessary to protect host
45
proteins made up of CCP modules are also called
regulators of complement activation
46
what is a lectin
a protein that can bind a carbohydrate
47
what molecules are not present on mammalian cells
lipoteichoic acid peptidoglycan (gram p)
lipopolysaccharide and peptidoglycan (gram n)
48
yeasts have what type of glycoproteins
terminal mannose residues
49
vertebrates have what type of glycoproteins
terminal sialic acid residues
50
what are PAMPs
pathogen associated molecular patterns
51
what are PRR
pattern recognizing receptors
52
what type of PAMPS
mannose, fucose, and acetylated sugars
53
what type of PRRs
mannose- binding lectin, ficolins
found circulating in blood
54
what are MBL
mannose-binding lectin
c-type lectin bind to mannose containing carb of bacteria, fungi, protozoa and viruses
55
structure of MBL
stalk is a triple helix made from three identical polypeptides
polypeptide provides carbohydrate recognizing domain "flower"
56
individual MBL have what level of affinity to mannose and fucose
very low
57
multimeric MBL has what affinity to mannose and fucose
high affinity
binding strength increase
58
MBL is produced where contains what
liver
consists of carbohydrate recognition domain
(CRD) flower
and a collagen like domain (stalk)
collectin
59
MBL monomer assembles into
trimers
60
2 to 6 trimers of MBL will
oligomerize with oligomers of 3 to 4 trimers
seen in blood
61
when MBL bind to surface of pathogen this triggers
lectin pathway of complement activation
62
Ficolin
consists of collagen like domain and fibronogen like domain, monomers assemble into trimers
63
humans possess 3 ficolins, where are they synthesized
2 synthesized in liver and circulate in blood
other secreted by lung and blood cells
64
in the blood MBL and ficolin oligomers complex with
MASP
MBL- associate serine proteases
65
MASP 1 and 2 are found as
inactive pro enzymes on stalk of MBL or Ficolin
66
step 1 of lectin pathway
MBL with MASP1 and 2 attach to surface of pathogen, conformational change occurs in MASP1, auto activation of MASP1 which then cleaves and activates MASP-2
67
difference between C4 and C3
thioester bond hidden further in C4
68
complement component of C2
a serine protease zymogen that is similar to factor B
69
step 2 of lectin pathway
active MASP2 cleaves C4 into C4 a and b
70
C4b can either attach to
water and become inactive or attach to pathogen surface and become active
71
step 3 of lectin pathway
C4b bind covalently bond to pathogen surface
72
step 4 of lectin pathway
active MASP2 cleaves c2 fragment into a and b
73
step 5 of lectin pathway
c2a is an active serine protease that binds to C4b on microbe surface and produces
C4bC2a
74
C4bC2a is the what like in alternative pathway
C3 convertase
75
Step 6 of lectin pathway
C4bC2a can cleave C3 molecules into C3b and a, allowing C3b to covalently bond to pathogen surface
76
lectin pathway is initiated by
activation of a specific PAMP and PRR interaction
77
what is the pathogen sensor of the classical pathway
C1 complex
78
what is the C1 complex made up of
C1q: collagen like domain and globular domain
monomers into timers
C1R and C1s (like MASP) are inactive serine proteases zymogens, two molecules of each protease assamble as a complex associated with C1q,
79
how can globular heads of C1q attach to pathogen surface
1. directly binding to certain bacterial cell wall structure such as lipteichoic acid
2. binding to c-reactive proteins that have adhered to surface of bacterium
3. bind to antibodies that have already bound to surface of pathogen
80
what are C reactive proteins (CRP)
pentraxin family of proteins
pattern recognition receptor
binds to phosphochoiline
cannot bind to that on mammals
81
classical pathway step 1a
C1 complex binds and if 2 or globular heads interact with ligand conformational change in C1r:c1s complex
82
classical pathway step 1b
conformational change in c1r:c1s complex causes autoactivatoin of C1r and active C1r able to cleave and activate c1s
83
Active C1s can cleave what substrates
C4 (similar to C3) and C2 (serine protease zymogen similar to factor B)
84
Step 2 of classical pathway
active c1s cleaves C4 to produce c4a and b
85
Step 3 of classical pathway
C4b molecule bind to surface of pathogen
86
c4a molecule becomes
mediator of inflammation
87
Step 4 of classical pathway
active c1s cleaves c2 into c2a and b, which is precursor to vasoactive c2kinin
88
step 5 of classical pathway
c2a is an active serine protease that binds to c4b on the microbe surface producing c4b2a (c3 convertase of classical pathway)
89
step 6 of classical pathway
one molecule of c4bc2a can cleave c3 into c3a and b. C3b can covalently bond to pathogen surface
90
what regulates CRP activation
recognition of a specific microbial signal/patter but both c1 complex, MBL and Ficolins can activate spontaneously
91
regulators of classical
DAF competes with face 2a for binding to c4b
MCP can associate with c4b2a convertase and displace 2a fragment, with help from cofactor I protease, cleaves c4b to inactive for iC4b
92
C1 inhibitor function
causes dissociation of either c1s/c1r from c1 complex and MASPs from MBL or ficolins
93
molecules involved with alternative pathway
C3, factor b, factor d and properdin
c3 convertase: ic2Bb and C3bBb
94
molecules involved with lectin pathway
MBL, ficolin, MASP1-2, C4 and C2
c3 convertase: C4b2a
95
molecules involved in classical pathway
C1q, C1r, C1s, C4 and C2
c3 convertase: C4b2a
96
all pathways lead to release of
C3a and binding of c3b to pathogen marking it for destruction
97
when C3b molecule combined with C3bB2 or C4bC2a it generates
a new enzyme called c5 convertase
98
what different about c5
two protein chains but no thioester bond
99
c5 binds to c3b in
c5 convertase complex
100
what happens to c5 convertase complex when c5 binds
conformation of complex change allowing Bb or the C2a serine proteases to cleave c5
101
c5b initiates
membrane attack
102
opsonization
coating the surface of a pathogen so that it is more readily ingested by phagocytosis
103
macrophages have what receptor that binds to C3b
CR1
104
macrophages have what receptor that binds to c5a
C5aR
105
C3b coated pathogen will bind to CR1 but is that enough for phagocytosis
no
106
C5a binding on C5aR will help do what to CR1
help phagocytos
107
c3a and c5a bind to
receptors on phagocytes, mast cells and endothelial cells and induce changes in the functions of these cells and alter the secretion of mulecules from the cells
108
what do C3a and C5a do to endothelial cells
increase blood flow and vascular permeability, leading to leakage of fluid from blood vessels and other complement and plasma proteins
109
C3a and c5a act also as what to recruit more phagocytes to site of injury
chemoattractants
110
C3a and 5a increase expression of complement receptors on
phagocytes
111
C3a and C5a cause what cell to degranualte and release histamine
mast cells
112
how does C5 initiate membrane attack
C5b binds to c6 (c5b6), then c5b6 complex binds to c7 (c5b67), causing conformational change of complex exposing hydrophobic site of c7 that inserts into lipid bilayer, c8 binds to c5b67 complex, another conformational change happens exposing hydrophobinc regiojn of c8 that inserts into bilayer, multiple c9 molecules bind to c5b678 complex until membrane spanning channel forms
113
what is MAC
membrane attack complex creates pore damages to lipid bilayer resulting in disruption of proton gradient, penetration of host cell enzymes like lysoyzome and eventual death of pathogen
114
