The complement system Flashcards Preview

Block 6 Week 1 > The complement system > Flashcards

Flashcards in The complement system Deck (107):
1

The (blank) is composed of more than 30 constitutively expressed proteins and their cleavage products that play and important role in the early stages of innate immunity.

complement system

2

What are the three pathways of complement activation that converge to make C3 convertases?

classical, lectin and alternative

3

What does C3 convertases generate?

opsonic C3b molecules on pathogen surfaces

4

Phagocytic cells recognize and destroy pathogens opsonized by (blank)

C3b

5

(blank) and (blank) bind to potentially harmful immune complexes and promote their blood clearance

C4b and C3b

6

(blank) and (blank) are anaphylatoxins that recruit and activate inflammatory cells

C5a and C3a

7

Formation of the (blank) promotoes assembly of the membrane attack complex (C6-C9) that kills certain bacteria

C5 convertase

8

complement is very potent so its activation is (blank)

tightly regulated

9

Deficiencies in complement results in what?

suscpetibility to microorganisms and immune complex diseases

10

a 67 year old women is hospitalized with a fever of unknown orgin. An elevate C reactive protein and erythrocyte sedimentation rate suggests an ongoing systemic inflammatory response. Which cytokine is especially important in these elevations?

IL 6 (remember that is the interluekin on the liver where c reactive protein will be found)

11

A 4 year old male presents with serious recurrent bacterial infections and has a big liver and spleen. an immunodeficiency disease is suspected, Everything is normal except a dihyrdorodamine test reveals that the patients neutrophils didnt reduce the dye. Why?

deficiency in NADPH oxidation

12

A 3 week old female with omphalitis has a diaper rash and bacterial pneumonia. Radiology is clear. Staph skin ulcer was looked at and there was very few neutrophils. What happened?

Deficiency in CD18

13

A 4 month old child has a staph skin infection without puss formation. has delayed umbilical cord separation and has some umbilicus. Has luekocytosis (too many whiteblood cells) but no b2 integrins. What immunological problem will this lead to?

Reduced diapedesis of neutrophils.

14

What is an important component of the immediate innate immune response to pathogens?

complement

15

How does the complement system work with the adaptive immunity?

works with antibodies in response to pathogens

16

The complement system is critical for innate and adaptive immunity. AND it plays an important role in eliminating (blank)

immune complexes

17

What does the complement system share with the coagulation and kinin systems?

cascades of proteolytic steps
zymogens (need to be cleaved to become activated)
amplification

18

What all can complements do besides kill?

they can cause inflammation, promote chemotaxis and activate immune cells

19

Some complement components can form (blank) in pathogen membranes that case lysis and death

pores (super rare)

20

What is the most important component of the complement?

its ability to opsonize

21

What do all three pathways of the complement system create?

C3 convertase

22

C3 convertase creates what 3 things?

C3b and C3a, C5a

23

What is the most important component of the complement system and why?

C3b because it is a potent opsonate

24

What does C3a and C5a promote?

inflammation and recruitment of phagoytic cells

25

What does C3B do?

removes immune complexes

26

What do terminal complement components do?

create pores in membrane

27

What is the order of the classical pathway?

C1, C4, C2, C3, C5-9

28

What does a capital letter designate?
What does a lower case letter designate?

complement
fragment

29

What is an A fragment, what is a B fragment?

A-> small fragment
B-> large fragment

30

What does a letter i indicate?

an enzymatically inactive form (can still bind to receptors)

31

In the classical pathway how are you going to detect pathogens?

by forming the the C1qrs complex

32

(blank) is a pattern recognition receptor that can bind to certain repeating molecular motifs on pathogens (e.g. bacterial porins and LPS)

C1q

33

What besides molecular motifs on pathogens can C1q bind?

IgM, IgG, or C-reactive protein deposited on pathogen surfaces

34

From the C1qrs complex how do you generate C3 convertase in the classical pathway?

C1q binds to pathogen surface, C1s beomes an active serine protease, this cleave C4 into C4a and C4b. C4b binds covalently to pathogen surface (or is hydrolysed), C1q then cleaves C2 and the large fragment associates w/ C4b. C4a floats away. This creates C4b2a which is the C3 convertase of the classical pathway.

35

What is cool about C3b and C4b?

if they are not instanteously bound to the microbe surface, water will come and hydrolyze it into an inactive substnace.

36

since ic3b is in active what can it do?

it works as a potent opsonate

37

Pathogens opsonized by (blank) are endocytosed and killed by phagocytic cells.

C3b

38

What three things have various receptors (CR3) for C3 and its breakdown products (iC3b)

macrophages, neutrophils and dendritic cells

39

What is the most important innat defense against extracellular pathogens

C3b mediated opsonization

40

What form complexes during infections and in some autoimmune diseases?

antigen/antibody

41

How do you get rid of immune complexes? (give detailed answer)

C1q binding results in deposition of C4b and C3b onto immune complex, C4b and C3b allows the immune complex to bind to CR1 (complement receptor 1) on RBCs. RBCs go through spleen and liver and immune complexes are stripped from the RBCs here and are degraded

42

Deficiencies in which three complexes can result in immune complex disease? WHat is an example of a disease such as this?

C1, C4, C2
Lupus

43

What is the lectin pathway?

it has mannose binding lectin (MBL) and Ficolins (similiar to the C1q in the classical pathway) and recognize certain patterns on pathogens. There are MASP 1/2 (like C1r/s) that act as proteases to create C3 convertase

44

THe (blank) pathway can amplify the classical and lectin pathway

alternative pathway

45

How can you engage the alternative pathway?

C3b deposited on a pathogen surface by the classical or lectin pathway

46

Explain the alternative pathway

C3b deposits and activates the pathway
Factor B binds to C3b
Factor D cleaves this into Bb
You now made C3bBb which is the new C3 convertase.
C3a which is left over is a potent anaphylatoxin and the C3bBb is stabilized by properidin

47

How do you stabilize C3bBb of the alternative pathway?

with properdin (factor P)

48

What happens to the small C3a fragment that isnt used to make the C3bBb in the alternative pathway?

it sticks around as a potent anaphylatoxin

49

What does C5 convertase do?

cleaves C5 into a large fragment called C5b and a small component called C5a

50

What are the two ways you can get C5 convertase?

classic pathway and lectin pathway (C4b2a3b) and alternative pathway (C3b2Bb)

51

What does C5b do?

triggers assembly of the membrane attack complex

52

What is C5a?

it is a potent anaphylatoxin

53

(blank) has the highest specific biological activity and isable to act directly on neutrophils and monocytes to speed up the phagocytosis of pathogens

C5a

54

(blank) works with C5a to activate mast cells, recruit antibody, complement, and phagocytic cells (chemotaxis), and increase fluid in the tissue (edema)

C3a

55

What is the least active anaphylatoxin?

C4a

56

Overexpression of (blank) can cause the medically important systemic anaphylaxis,

anaphylatoxins

57

What are anaphylatoxins?

they are complement fragments that are chemotactic agents and promotors of inflammation.

58

If (blank) binds to its receptors on a phagocytic cell, this phagocytic cell will increase phagocytosis 10 fold.

C5a

59

HOw do you change a C3 converatase into a C5 convertase?

by adding a C3b molecule to it

60

What does C3a and C5a do?

peptide mediators of inflammation, phagocute recruitment

61

What does C3b do?

binds to complement receptors on phagocytes-> opsonization of pathogens, removal of immune complexes

62

What do terminal complement components do;
C5b, C6, C7, C8, C9

membrane-attack complex, lysis of certain pathogen and cells

63

Explain the membrane attack complex

C5b will call over C6 and C7 and form a complex. C7 will burrow the complex into the lipid bilayer of the cell. Then C8 will be called over to do the heavy work and will really borrow the complex in the bilayer. Then a bunch of C9 will polymerize and form a pore with the complex and those destroy the cell

64

the MAC (membrane attack complex) is awesome but only can really kill which 2 microbes?

Neisseria meningitidis
Neisseria gonorrheae

65

Most common deficiency is (blank)

mannose binding lectin deficiency

66


If you have low levels of complement does that mean you have a complement deficiency?

no, it could mean that you had a large infection and your using up your complement so your immune system is functioning fine

67

What are three deficiencies you can get in the classical pathway and what will this lead to?

C1
C2
C4
leads to immune complex disease

68

What are 5 deficiencies you can get in the MBL pathway (mannose binding lectin)?

MBL
MASP1
MASP2
C2
C4
deficiency of MBL leads to bacterial infections mainly in children

69

What are 2 deficiencies you can get in the alternative pathway?

Factor D
Factor P
deficiency leads to infection with pyogenic bacteria and neisseria but no immune complex problems

70

What is the most common complement deficiency

MBL

71

Why does a deficiency in the classical pathway make us have immune complex disease?

because C4 tags immune complexes

72

What happens if you have a deficiency in C3?

infection w/ pyogenic bacteria, Neisseria, immune complex disease and often death

73

What will a deficiency in the membrane attack complex cause?

if C5-C9 are deficient you can be susceptible to Neisseria only (gonnorhea or menigitidis)

74

How can you tell if you have a reduced amount of complement is due to a genetic issue or just depletion from an infection?

if its infection, then all of your complements should be reduced rather than only one specific complement being reduced

75

When complement is activated by pathogens, multiple components are temporarily (blank)

depleted

76

When you work up complement deficiencies, what do you use to make a diagnosis>

the membrane attack complex

77

How does the membrane attack complex tell you whether or not you have a complement deficiency?

You use either a CH50 assay (to assess classical pathway or terminal pathway) or the AH50 assay to assess the alternative pathway and tag RBCs with antibodies and add serum from patient. If there is hemolytic complement actiivity it will bind to the antibodies and cause lysis of the RBC. SOOOO if there is no lysis occuring then there is a deficiency.

78

What does a low level of boh CH50 and AH50 suggest?

there is deficiency of one of the components shared by both pathways which could be C3-C9

79

What does a low AH50 with normal CH50 suggest?

a deficiency in factor B, Factor D, or properdin

80

(blank) are used to demonstrate specific complement protein deficiencies

immunoassays

81

What does Low C3 and C4 levels indicate?

activation of the classical pathway

82

What does low C3 ad normal C4 levels suggest?

activation of the alternate pathway

83

What happens if you have a deficiency in MBL?

pyogenic bacterial infection in children, common in lupus, compensation w/ opsonic antibodies

84

What is the second most common complement deficiency?

C2 (problems with classical pathway)

85

What happens if you have a C2 deficiency?

prevents formation of C3 convertase and thus lack of removal of immune complexes.

86

(blank) is a three chain molecule, and deficiency in Caucasians is caused by mutations in the beta chain.

C8

87

Recurrent neisserial infections strongly suggest a defect in a component of the (blank), or of factors (blank and blank) of the alternative complement pathway.

membrane attack complex (C5-C9)
D and P

88

Is the complement system potent?

yes, very potent and must be tightly controlled to prevent tissue damage

89

A variety of (blank) have been identified that control all three complement pathways

complement regulatory proteins

90

Deficiency in reglatory proteins can lead to what?

tissue damage
depletion of complement components
increased susceptibility to infections and immune complexes

91

What disease can you get with deficiency of CD59?

paroxysmal nocturnal hemoglobinuria

92

What are these:
C1 inhibitor (C1INH)
C4-binding protein (C4BP)
Complement receptor 1 (CR1)
Factor H (H)
Factor I (I)
Decay-accelerating factor (DAF)
Membrane cofactor Protein (MCP)
CD59 (protectin)

complement regulatory proteins

93

(blank) is a protease inhibitor belonging to the serpin superfamily. Its main function is the inhibition of the complement system to prevent spontaneous activation

C1-inhibitor

94

What is this:
diminished C4 levels but C3 levels are normal. swelling of lips and hands. Deficiency of C1 inhibitor.

hereditary angioedema

95

Hereditary angioedema (HAE) is caused by a deficiency in the (blank)

complement regulatory protein C1 inhibitor (C1INH)

96

C1INH is a serine protease inhibitor that prevents (blank) overactivation of the classical complement pathway

C1r and C1s

97

Why do you get the clinical manifestations (swelling) that you see in HAE?

because C1 INH usually inhibits a serine protease that (when not inhibited) increases vasodilation through bradykinin

98

Where does bradykinin cause recurrent swelling?

skin, ntestine, airways

99

How can you make the diagnosis of HAE (hereditary angioedema)?

very low C1INH and low C4 levels
C3 levels normal

100

HOw do you treat C1INH?

human recom C1INH
(HAE resembles anaphylaxis but epinephrine wont fix this problem)

101

What is this:
diminished C4 levels but C3 levels are normal. swelling of lips and hands. Deficiency of C1 inhibitor.

hereditary angioedema

102

Hereditary angioedema (HAE) is caused by a deficiency in the (blank)

complement regulatory protein C1 inhibitor (C1INH)

103

C1INH is a serine protease inhibitor that prevents (blank) overactivation of the classical complement pathway

C1r and C1s

104

Why do you get the clinical manifestations (swelling) that you see in HAE?

because C1 INH usually inhibits a serine protease that (when not inhibited) increases vasodilation through bradykinin

105

Where does bradykinin cause recurrent swelling?

skin, ntestine, airways

106

How can you make the diagnosis of HAE (hereditary angioedema)?

very low C1INH and low C4 levels
C3 levels normal

107

HOw do you treat C1INH?

human recom C1INH
(HAE resembles anaphylaxis but epinephrine wont fix this problem)