Inflammation 2 Flashcards
(162 cards)
1
Q
complement initiated by
A
soluble PRRs
2
Q
during complement pathway get release of cleavage products, many components in complement pathway activated by
A
proteolytic cleavage
3
Q
split products are
A
cleavage products that are released following activation of components of complement pathway
4
Q
most acitivation of compeent component srequire
A
enzymatic cleavage
5
Q
complement is important in inducing
but
A
inflammatory response
it can also cause damage to our own cells
6
Q
don’t want complement activation on
A
surface of own cells - they can lead to lysis of own cells
7
Q
complement consist of
A
30 plasma proteins
secreted as inactive proenzymes
8
Q
activation of most inactive proenzymes of compleent requried
A
activation of proteolytic cleavage
9
Q
during inflammatory response you get enhance activation of
A
complement
10
Q
most importan function of complement in innate response
A
generate opsinin c3b
when c3b is generated covalently bind to surface ofp athogens - that acts as little flat on surface of that pathogen telling phagocyte to eat it
greaterly increases efficiency of phagocytosis
11
Q
phagosytosis without opsinization is
A
very inefficient
12
Q
opsinization knows what to destroy b/c
A
it has receptor for opsinin on its surface
13
Q
when opsinin binds to bacterium the other end
A
binds to opsinin receptor on phagocyte - really high effincity -greatly enhance efficiency of phagocytosis
14
Q
generate a lot of opsinin b/c c3 is
A
very abundant in plasma (c3 is most abundant complement component and is precurser to c3B)
15
Q
important complement innate function
A
tell phagocyte to come in
16
Q
c3a, c4a, c5a are
A
anaphylatoxin
17
Q
c3a, c4a, c5a, number of affects, what are they:
A
vasculature - allows to bring more cells to area
chemoattractants - potent especially for neutrophils
stimulate mast cells
18
Q
once c3a c4a c5a call neutrophils, what needs to happen in tissue for neutrophils to get from circulation to infected tissue
A
mast cells need to be activated
19
Q
at end of complement cascade the complements come together in formation of a
A
pore
20
Q
pore is called
A
mac
21
Q
mac stands for
A
membrane attack complex
22
Q
encapsulated bacteria, will they be sensitive to mac
A
no
23
Q
gram + bactiera will they be sensitive to mac
will gram - be sensitive to mac
A
gram + not sensitive
gram - yes senesitive - this allows the outer part of gram neg to be taken away and the peptidoglycan part revealed
24
Q
alternative and lectin pathway happend directly where
A
on surface of microbes or pathogens
25
classical pathway can only be activated following
antibody binding to antigen
| usually requires adaptive response and production of antibody
26
initaters of complement activation recognize
PAMPs
27
3 complement pathways come together at the activation of
C3 (into C3a and C3b)
| C3 is activated by cleavage
28
first to act, second to act, third to act of the complement activation pathways
1. alternative pathway
2. lectin
3. classical
29
does alternative pathway require recongnition
no its always on
30
complement activation is the same as (another name for it)
complement fixation
31
what are the three pathways by which complement can become activated
1. alternative pathway
2. lectin pathway
3. classical pathway
32
C3a and C5a recruit
| C3a and C5a activate
phagocytes
| mast cells
33
why is alternative pathway first to act
it is happening all the time
it's a result of spontaneous hydrolysis of component c3 which is always happening at a low rate
it won't go further unless there is pathogen surface
34
do lectin and classical pathway require recognition
yes
35
why is classical pathway the last to act
requires adaptive immune response
36
lectin pathway activated by
recognition of structures common to microbes and pathogens but not commonly found on our own cells
37
end result of the activation events
formation of enzyme that will cleave the most abundant component of complement: c3 - into c3a and c3b
38
c3b is the most important
opsinin
39
which are the chemoattractants
c5a
c3a
c4a
40
what initiates the alternative pathway
c3b binding to surface of pathogen
41
surface bound c3b now becomes binding site for plasma protein called
factor B
42
factor B binds to c3b and then what happens
factor B undergoes conformational change that makes it susceptible to cleavage by plasma protease called factor D
43
C3b is generated and covalently binds to
surface of pathogen
44
once C3b binds to pathogen and on its surface becomes binding site for
factor B
45
when factor B binds to C3b what happens
it undergoes conformational change that makes factor B susceptible to cleavage by plasma protease called factor D
46
some of c3b will bind to
enzyme that generated it and turn it from c3 converates to c5 convertase
47
properdin
binds to protects c3 convertase
48
absense of properdin
c3 convertase cleaved by factor I
49
in alternative pathway C3 convertase is
C3bBb
50
bacteria opsinized by
c3b
51
c3a diffuses and recruits
phagocytes
52
c3a is
chemoattractant
53
c3a has affects on blood vessels to allow
phagocytes to pull themselves through bood vessel walls and get into tissues
54
opsinization works
b/c phagocytes haveon surface receptor for other end of c3b, makes inefficient process very efficient
55
what is most important opsinin generated during complenet activation
c3b
56
what opsinin beside c3b important
c4b
| Igg
57
Igg during adaptive response binds to
surface of pathogen and the other end (stem of y) binds to receptor
58
stem of Igg is called
Fc portion of Igg
59
receptor taht binds to stem of Igg called
Fc receptor
60
IgM and Igg are
two different types of antibodies
61
IgM is not
opsinin
62
IgM and Igg can also activate
complement pathway
63
in all pathways come c3b generated that some binds to
enzyme that generates it
64
when c3b binds to c3 convertase that enzyme is now
c5 convertase
65
c5 convertase
converts c5 into c5a and c5b
66
c5a does what
goes away and attracts more phagocytes
67
c5b does what
binds
68
lectin and classical pathway have to have
recognition
69
lectin recognition - what does it recognize
sugar residues by lectin
70
what does lectin pathway specifically recogniae
mannose-binding lectin (MBL)
| ficolins
71
MBL stands for
mannose-binding lectin
72
MBL and ficolin belong to
same family
73
associated with heads of ficolin and MBL are
enyzmes
74
once ficolin and MBl binds to something it triggers
conformational change which activates the first enzyme
75
what are enzymes called on ficolin and MBl
MASPS
76
how many MASPS
1 & 2
77
MASP 1 activated by
conformational change
78
MASP 1 does what
cleaves and activates MASP 2
79
MASP 2 does what
cleaves c4 into c4 a & b
| and c2 into c2a and b
80
pathogens have terminal
mannose residues on glycose proteins
81
c4a
goes away
82
c4b
site of generation of c3 convertase of lectin pathway. binds to surface
83
c2a
binds
84
c2b
diffuses - don't know the function
85
c2a binds to
c4b (convertase, same as in the other pathway)
86
in lectin pathway c3b functions as
opsinin
87
classical pathway needs to be activated by
antibody
88
antibody generated during
adpative resopnse
89
1st component of classical pathway
c1
90
c1 complex made of
c1q - c1r & c1s (two molecules of each of them associated with c1q)
91
c1q binds to
Fc portion of antibody molecule when that antibody has bound to antigen (it will not bind to circulating antibody not bound to antigen)
92
when c1q binds to Fc what happens
undergoes conformational change and is active
| cleaves and activates c1s
93
active c1r does what
cleaves and activates c1s
94
c1 molecule has to associate with how many
2 molecules close together - need two fc regions close together in order to activate the classical pathway
95
antibody molecule that naturally has 2 or more fc domains
IgM
96
IgM is what kind of antibody
pentomer
97
one molecule IgM already has
two Fc regions close together
98
one molecule of IgM binding to C1 is
sufficient to activate classical pathway
99
draw classical pathway
pg 22
100
to activate classical pathway with IgG
need two IgG molecules bound close together
101
what is most efficient antibody at activating complement
IgM
102
one exception to classical pathway activtion
when molecule called CRP (c-reactive protein) binds to lipids commonly found on surface of pathogens (phosphorycholine) that allows c1q to bind directly to crp
103
at the stage of C3 convertase in all three pathways will generate a lot of
c3b
104
when c3b binds to the enzyme that generated it (c3 convertase) what does it do
turns c3 convertase into c5 convertase
| alters the specificty of the enzyme
105
c5 convertase cleaves
c5 - to c5a and c5b
106
c5a is a potent
| it also potently increases
chemoattractant
| vascular permeabilty - causes endothelial cells to be able to be pulled apart more
107
c5b is frist step in formation of what
first step in formation of membrane attack complex
108
at what point would you begin to form the pore
at c5b
109
MAC only perferates
membrane - envelope it would perforate, unencapsulated gram neg. bac. are as well
110
c3a & c5a diffuse away and attract
leukocytes (esp neutrophils)
111
c3a & c5a cause endothelial vessels lining blood vessel
to pull apart
| enhances complement activation where infection is
112
important step to allow endothelial vessels lining blood vessel to pull apart is
mast cells
113
c3a and c5a activate what cells to de-granulate
mast cells
114
c5b generated from c5, once generated what binds to it
c6
115
c7 binds to
c6
116
c7 does what
attaches complex to membrane
117
c8 binds to
c7/complex
118
multiple molecules of c9
inserts across the memberane forming pore - results in lysis of pathogen
119
c8 goes
into the membrane
120
to be lysed by membrane attack compelx MAC need to have
available membrane. so gram neg. more susceptible to lyssi by mac
121
formation of MAC starts with
c5b
122
what initiates mac contact with membrane
c7
123
c8 does what
inserts across membrane
| "c8 goes on a date - with the membrane"
124
c9 does what
forms pores across membrane
125
for c3b to funtion as opsinin ahs to be recognized by
receptor on phagocyte
126
cr1
receptor for c3b & c4b
127
cell that expresses cr1 has to be exposed
to c5a to be an opsinin
128
main receptor for opsinin
cr1 & cr3 & cr4
129
receptors on phagocytes for chemoattractats
c5a & c3a
130
receptors on mast cells for chemoattractsns
c5a & c3a
131
most complemet control proteins function by
destabilizint of convertases and ultimately degradation of convertases by factor I
132
c1 inhibitor
removes enzymes from c1 complex and from fycolins and MBL
| removes c1q and removes MBL
133
can block lectin and classical pathway at start using what
C1 inhibitor
134
just memorize the chart of regulatory proteins in classical and alternative pathways
pg 33
135
if you destaiblize c3 convertase will never generate
c5 convertase
136
factor I of plasma protease will
cleave what has been displaced
137
MCP is active in which pathways
alternative and lectin pathways
138
decay acceleration factor
slows acceleration of c3 convertases
139
DAF stands for
| what does it do
decay accerlerating factor - accelerates decay of convertases
140
CD59
prevents insertion of c9 across the membrane
| prevents formation of pore membrane attack complex
141
C1 inhibitor removes enzymes from
initiatiors of classical and lectin pathway
142
defficient levels or defective C1 inhibitor is what disease
Hereditary Angioedema - HAE
143
C1 inhibitor prevents production of what part of acute inflammation
bradykinin
144
bradyknin is
potent inducer of vascular permeability
145
disregulated production of bradykniin leads to
increase in vascular permeability at the point of trauma - so movement of fluid into the tissue leading to swelling (hereditary angioedema)
146
iC3b fragments can function as
opsinin - but do not have active convertase. only incative in terms of convertase activity
147
DAF, MCP, C4BP, CR1
dirsupt c3 convertase formation
148
c3 convertase necessary to generate
c5 convertase - will nver form the pore
149
c5 convertase required for genreation of
c5b
150
CD59 binds to
c5b678
151
cd59 prevents
echo 11:10
152
no functional cd59 is what disease?
Paroxysmal Nocturnal Hemoglobinuria - PNH
153
most sensitive cells to complement mediated lysis
RBC
154
PNH stands for
Paroxysmal Nocturnal Hemoglobinuria
155
result in de novo mutations in gene that is required to anquor the complemetnt regulatory proteins to the cell memvrane
PNH
156
when factor D cleaves factor B it splits off what fragment
| what remains bound to C3b
Ba
| Bb remains bound to C3b
157
C3b functions as an
opsinin
158
What is the CD name for DAF
CD55
159
What is the CD name for MCP
CD46
160
write out the diagram (or understand)
pg 42
161
write out the diagram (or understand)
pg 43
162
understand the diagram
pg 44
