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MSS-IHL Final Exam > Complement Cascade > Flashcards

Complement Cascade Flashcards

0
Q

what systems does complement “complement”?

A

humoral and innate immunity

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1
Q

C’

A

complement

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2
Q

complement is central to what?

A

inflammatory reactions

triggering and amplifying inflammation, attraction of phagocytes, clearance of immune complexes, cellular activation, direct microbial killing, and important in development of the humoral responses

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3
Q

larger and smaller fragment of complement?

A

a - smaller
b - larger

b binds and a diffuses

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4
Q

anaphylotaxins

A

a fragments of complement

are chemotactic peptides

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5
Q

role of anaphylatoxins

A

play a role in initiating a localized inflammatory response

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6
Q

all pathways of complement end where?

A

formation of the MAC

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7
Q

classical pathway

A

activated by antigen binding to antigen

assists in the humoral response

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8
Q

alternative pathway

A

not necessary for a prior exposure
-doesn’t need antibody
plays a role in surveillence

more primitive than classical

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9
Q

lectin pathway

A

activated by binding of mannose binding protein in bacteria

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10
Q

initiation of classical pathway?

A

IgG or IgM antibody is bound and results in the binding of C1
-C1 binds to Fc portion of antibodies

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11
Q

overview of classical complement pathway

A

most efficient and fast

1) IgG and IgM antibodies bind antigen and Fc portion binds C1
-binds to C1q domains (cleavage of C1r and C1s)
enzymatically active C1qrs

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12
Q

structure of C1

A

one hexamer C1q subunit, two C1r, and two C1s subunits

forms a large complex
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13
Q

what activates C1?

A

cleavage of C1r and C1s
-yields active C1qrs

*the C1 is a C1q hexamer, two C1r, and two C1s subunits

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14
Q

how many of each antibody to activate classical pathway?

A

IgM is a pentamer
-only requires one to initiate cascade

IgG is a monomer
-requires at least two to initiate cascade

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15
Q

activity of enzymatically active C1qrs?

A

cleaves C4
-release C4a and C4b

C4b attaches to the cell membrane which form clusters around the area of the antibody interaction

C4a diffuses away

also cleaves C2

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16
Q

activity of C4b?

A

recruits C2, which is also cleaved by C1qrs

-C2a diffuses away and C2b binds to C4b

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17
Q

what is the C3 convertase of classical pathway?

A

C4b2b
-cleaves C3

C3b will opsonize and also associate with the C3 convertase
-forms the C4b2b3b (C5 convertase)

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18
Q

importance of C3

A

responsible for the distinction between self and non-self

self surfaces limit the deposition of C3b
-C3b rapidly associates with non-self surfaces

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19
Q

C5 convertase of the classical pathway?

A

C4b2b3b

initiates the formation of the MAC complex

C5b associates with C6 and C7 which inserts into the membrane
-forms pore - which will lead to slow lysis

C8 then bind the C5b67 which
-forms C5b678 which recruits 10-16 copies of C9
forms the MAC

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20
Q

what is the MAC complex?

A

C5b6789

creates large pores in the membrane
-results in more rapid osmotic lysis of the cell

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21
Q

alternative pathway of complement?

A

slow and less efficient

surveillence system

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22
Q

initiation of alternative pathway?

A

spontaneous conversion of C3 to C3b

-important in recognizing self from non-self

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23
Q

how is C3b involved in the recognition of self membrane?

A

sialic acid levels are high on the self membranes
-result in the inactivation of C3b

bacterial and viral envelopes have low sialic acid
-C3b remains associated with membrane

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24
C3 convertase of the alternative pathway?
factor B binds to C3b and is cleaved -factor D cleaves factor B ``` forms C3bBb (alternative C3 convertase) results in the cleavage of C3 (amplifies process) ```
25
Factor B
binds to membrane associated C3b cleaved by Factor D
26
Factor D
cleaves factor B bound to C3b | -results in C3bBb (C3 convertase of the alternative pathway)
27
properdin
binds the C3 convertase of alternative pathway and stabilizes it *increases its half-life
28
C5 convertase of alternative pathway?
C3bBbP3b Properdin is stabilizing the C5 convertase C5 convertase cleaves C5 and formation of MAC complex occurs
29
lectin pathway?
antibody-independent involves the lectin -MBLs and MASPs
30
activation of the lectin pathway?
MBL binds MASP on bacterial surface polysaccharides this structure is similar to the C1q -cleaves C4 and C2 ``` forms C4b2b (C3 convertase of the classical pathway) -everything occurs as classical pathway forms the C3 convertase C4b2b ```
31
RCA proteins?
regulators of complement activation
32
two main function of RCA?
bind and cause dissociate cause the proteolytic cleave of components
33
first level of control of convertases?
decay acceleration
34
decay acceleration
many of the components have short half lives C3b is hydrolyzed rapidly**
35
C1inh
in both classical and lectin pathway binds to the C1r and C1s to dissociate them from C1q removes MASP enzymes from MBL complex
36
Factor I
plasma protein cleaves C4b or C3b has several cofactors - C4-bp, MCP, CR1 prevents formation of C3 and C5 convertases - C3 - C4 degradation - C5 - C3 degradation
37
cofactors of Factor I
C4-bp, MCP, CR1
38
C4-binding protein
binds to C4b - prevents its association with C2b - causes C4b to dissociate from the C3 convertase C4-bp/C4b is target for digestion by Factor I
39
Complement Receptor I
binds C3b and allows for the cleavage by Factor I **mechanism for distinguishing between self and non-self (CR1;CD35)
40
Membrane Co-factor protein
MCP;CD46 co-factor for factor I binds to either C4b or C3b found on self membranes *allows self vs. non-self recognition
41
Factor H
analagous to C4-bp binds to C3b and prevents C5 convertase formation Factor H/C3b is a target for factor I
42
protected site concept
factor H binding only occurs if the C3b has been deposited on surface of cell
43
decay-accelerating factor
DAF;CD55 promotes the dissociation of the C3 convertase - C2b from C4b and Bb from C3b - in classical and alternative pathways
44
CD59
blocks C9 binding to C5b678 on cell surface
45
vitronectin (S protein)
binds to the fluid phase (C5b67) -prevents binding to membrane * *doesn't prevent C8 or C9 association - forming MAC, but they aren't in the membrane
46
opsonization -major one in body?
major one is C3b C4b is also an opsonin Complement receptors on the phagocytic cells bind to the C3b or C4b - increases phagocytosis - also the a fragments increase phagocytosis
47
activity of anaphylatoxins?
increase the number of complement receptors on the cell surface of phagocytes greatly facilitate their phagocytosis of complement opsonized cells
48
waste management
removal of immune complexes from circulation -antibodies bind extracellular antigens antibody with bound C3b - binds to erythrocytes complement receptor - taken to the spleen and liver (degradation) - erythrocytes offload the antibody/complement
49
MAC activity on erythrocytes?
only single MAC to lyse an RBC
50
nucleated cells and MAC?
usually requires several MACs there are certain cells that can internalize the MAC and degrade it
51
complement and inflammation?
instrumental role activation of complement results in influx of fluid
52
anaphylatoxins function?
increase inflammation bind to receptors on mast cells and basophils - histamine smooth muscle contraction - vascular permeability monocytes and neutrophils to adhere to endothelial cells
53
C5a
most potent in mediating the processes of inflammation in response to complement cascade
54
C2a
prokinin cleaved by plasmin to yield kinin -results in edema
55
C3 deficiency
can lead to life-threatening situations -noticed early after birth can be mimicked by deficiency in factor H and factor I **why?
56
MAC deficiency?
C5, 6, 7, 8, 9 generally healthy except infection by Neisseria gonorrhoeae and N. meningitidis
57
deficiency in C1, 2, and 4
most common is C2 -patients have a high degree of systemic lupus erythematois SLE
58
C1inh deficiency
HANE chronic low levels of C4 and C2 swelling with no obvious cause commonly involves the extremities
59
DAF deficiency
decay-accelerating factor leads to paroxysmal nocturnal hemoglobinuria hemolytic disorders -degrades RBCs treat with erythropoietin
60
viruses and complement?
use them to increase its infectivity epstein-barr - CR2 as a receptor for attachment measles - MCP as a receptor West Nile virus - C3b to gain entry into cells via CR3 recepor

MSS-IHL Final Exam (15 decks)

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