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Immunology (a) > the complement system > Flashcards

the complement system Flashcards

0
Q

complement proteins are normally found in

A

plasma and among the plasma proteins that leak out of the capillaries into the tissue spaces

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1
Q

complement system

A

consist of approximately 20 heat- liable serum and cell surface proteins, many of which are enzyme precursors that must be cleaved to form active enzymes

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2
Q

complement proteins are synthesized by the

A

liver and macrophages

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3
Q

Juleus Bordet concluded that the lytic effect required two factors:

A

1) specific antibody

2) heat- liable component present in normal serum

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4
Q

Paul Ehrlich called the labile component _____, since it was thought to assist or complement the lytic function of antibodies.

A

complement

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5
Q

two main pathways for complement activation:

A

1) classical way

2) alternative pathway

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6
Q

classical pathway is initiated by:

A

antigen-antibody (IgM or IgG) complexes

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7
Q

alternative pathway is initiated by:

A

microbial surfaces

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8
Q

Both of the pathways for complement activation lead to the production of

A

C3b, the central molecule of the complement cascade

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9
Q

C3B can combine with other complement components to generate

A

C5 convertase

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10
Q

C5 convertase

A

this enzyme leads to the terminal pathway that produces the membrane attack complex (MAC)

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11
Q

when the complement system is _____, multiple products are formed that preform a variety of biological functions, including ___ ___ ___.

A

activated

cell membrane lysis

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12
Q

C3 is

A

the most abundant complement protein

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13
Q

the enzyme cascades are generated by the sequential ____ ____ of enzyme precursors (______ or ______) to generate enzymes with proteolytic activity. In the process, an inhibitory fragment (____(“a”)) is removed, exposing the active site on the ____ ____ (“b”).

A

proteolytic cleavage
proenzymes or zymogens
small fragment
major fragment

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14
Q

regulatory proteins present in serum and on host cell membranes ___ or ____ complement-mediated damage.

A

inhibit

minimize

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15
Q

T or F:

Since microorganisms lack these regulatory proteins, complement activation is allowed to occur on microbial surfaces.

A

T

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16
Q

proteins of the classical pathway

A

C1( C1qr2s2)
C2
C3
C4

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17
Q

proteins of the alternative pathway

A

C3
Factor B
Factor D
Properdin

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18
Q

the classical complement pathway

A

is initiated by binding of C1 to the Fc regions of IgM or IgG molecules that have bound to antigen

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19
Q

C1 is composed of 3 subunits:

A

C1q and two molecules each C1r and C1s held together by non-covalent and stabilized by calcium ions

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20
Q

C1q

A
  • Cannot bind to free or soluble IgM or IgG
  • six globes held on slender shafts that fuse into a common base
  • globes are recognition unit
  • when IgM or IgG binds to its antigen, its active site on the Fc region is exposed to C1q
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21
Q

each IgM or IgG Fc region possesses only ___ C1q-binding site, and each C1q molecule must bind to ___ Fc regions to be activated.

A

one

two

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22
Q

T or F:

IgM is a much more efficient complement-binding antibody than IgG

A

true

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23
Q

C1r

A
  • serine protease
  • binding of two or more of the globular heads of C1q to IgG or IgM induces a conformational change in C1r, converting C1r to an active protease enzyme that is able to cleve and activate C1s
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24
Q

C1s

A
  • serine protease

- once it is activated it cleaves C4 into a larger C4b fragment adn a smaller C4a fragment

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25
Q

C4b fragment

A
  • has an internal thioester bond that binds to the target cell membrane in the vicinity of C1
  • when unbound decays in the medium
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26
Q

C4a fragment

A

is released into the fluid phase

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27
Q

C2

A

proenzyme binds to the exposed binding site on the cell- bound C4b to form C4bC2 complex; C2 is cleaved by a nearby C1s molecule into a soluble C2a fragment and C2b

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28
Q

classical C3 convertase

A

C2b remains bound to C4b to form an enzyme complex C4b2b

29
Q

substrate modulation

A

C1s cannot act on C2 unless it is bound to C4b

30
Q

C3

A
  • activated by proteolytic cleavage

- C4b2b binds to and proteolytically cleaves C3 into C3b and a small C3a fragment

31
Q

a single C3 convertase enzyme can generate more than ___ molecules of C3b, resulting in tremendous ____ at this step of the complement cascade.

A

200

amplification

32
Q

there are 3 things that C3b can do:

A
  • can bind to c3 convertase to form the C5 convertase
  • can bind directly to cell membrane in the vicinity of C4b2b
  • some diffuse away and coat immune complexes (antigen-antibody complexes) and particulate antigens, eg, bacteria, functioning as opsonin and promoting phagocytosis
33
Q

C5 convertase

A

C3b cmponent of the complex binds C5 and alters it conformation, so that the C4b2b component can cleave C5 into C5a and C5b

34
Q

C5a

A

is released into the fluid phase

35
Q

C5b

A

remains attached to the C5 convertase, initiating the terminal pathway of the complement activation.

36
Q

alternative complement pathway

A

-described by pillemer
system for activating complement begining at C3, which does not involve an Ag-Ab reaction but by binding of complement protein C3b to the surface of a patogen

37
Q

microbial structure that can activate the alternative pathway include:

A

lipopolysaccharide
teichoic acid
zymosan
viral envelopes

38
Q

Alternative pathway is ____ important than the classical pathway the ___ time an individual or animal is infected by a microorganism, because the ___ or ___ required to trigger the classical pathway is not present

A

more
first
IgG
IgM

39
Q

the thioester bond in C3 can be cleaved by:

A

plasmin
phagocyte
proteases
trypsin

40
Q

C3b binding to host cell surfaces is inactivated by :

A

factor H and I

41
Q

Factor H has an affinity for ___ constituents of host cell membrane glycoproteins and this ___ its binding to any C3b deposited on host cells

A

sialic acid

increase

42
Q

some bacteria may express high levels of sialic acid on their cell surfaces or they may scavange sialic acid from the host and enzymatically transfer the sugar to their cell surface. this can ____ the alternative pathway by enhancing the binding of factor ___ to ___ on the bacterial membrane

A

inhibit
H
C3b

43
Q

factor d

A

factor B binds to C3b undergoes substrate modulation and is cleaved by factor D to yield a soluble fragment, Ba and a larger fragment Bb that remains attached to C3b

44
Q

C3bBb

A

is the alternative C3 convertase and it cleaves more C3 molecules, initiating anamplification sequence for C3b

extremely unstable unless bound to properdin

45
Q

C5 convertase

A

C3b generated by C3 convertase can bind to the convertase.
his results in the formation of C3bBb3b complex, which functions as the alternative C5 convertase to cleave C5 and initiate the terminal pathway

cleaves C5 into a soluble C5a and C5b.

46
Q

C5b67 complex

A

undergoes a conformational change, causing its release from the C5 convertase and exposing hydrophobic regions that enable the complex to bind to membrane phospholipids

when bound binds to C8

47
Q

C5b678 complex

A

is responsible for slow membrane leakage. a fully active MAC is accomplished by the polymerizaion of up to 18 molecules of C9 to form a tubular pore in the cell membrane, allowing the entry of water and ions

48
Q

complement receptors

A

cell surface proteins on various cells which recognize and bind to various complement fragments
this facilitates the effector functions of complement

49
Q

most of the effector functions of the complement are mediated by binding of _____ fragments of complement proteins to various cell surface receptors.

A

proteolytic

50
Q

only cell lysis is mediated by the

A

MAC

cells include:
erythrocytes, Gram negative bacteria, tumor cells, and enveloped viruses

51
Q

__________ are not susceptible to the mAC because their cell membranes are protected by the thick peptidoglycan layer

A

Gram positive bacteria

52
Q

chemotactic fragments include:

A

C5a, C3a, C5b67

chemotaxis of monocytes/macrophages and polymorphs

53
Q

___,_____, and ___, bound to microbial surfaces can simultaneously bind to complement receptors on neutrophils and macrophages, stimulating engulfment and intracellular killing

A

C3b, C4b, iC3b

54
Q

___>___>___ bind to mast cells and blood basophils and induce degranulation with the release of histamine and other vasoactive mediators. the mast cell reactions result in influxes of phagocytic cells and plasm proteins to the site of microbial invasion.

A

C5a, C3a, C4a (anaphylatoxins)

55
Q

C5a and C3a

A

bind to their receptors on endothelial cells inducing the expression of P selectin and vascular permeability, events that promote leukocyte extravasation into tissue

56
Q

P-selectin

A

promotes neutrophil binding

57
Q

anaphylatoxins can also bind ___ to smooth muscle cells of the bronchioles and cause______.

A

directly

bronchospasm

58
Q

activation of phagocytes involves:

A
  • rearrangement of integrin adhesion molecules
  • increased expression of CR1 and CR3
  • stimulation of the respiratory burst and production of reactive oxygen intermediates
  • release of inflammatory cytokines, proteases
59
Q

Bb

A

activates macrophages, ausing them to adhere to and spread on surfaces, thus inhibiting macrophage migration from the site of antigen deposition

60
Q

the central role of C3b

A
  • binds to factor B, C5 and cellsurface proteins and polysaccharides
  • nonspecific opsonin
  • clearance of immune complexes from the circulation
  • selection of B calls in germinal centers
  • source of iC3b, C3d, etc
61
Q

Uncontrolled activation of complement can:

A
  • rapidly deplete complement proteins
  • lead to formation of MAC on normal host cells
  • result in excessive generation of inflammatory mediators
62
Q

regulation of complement is mediated by:

A

circulating and cell surface proteins

63
Q

spontaneous decay of activated complement components include:

A

time and temperature dependent dissociation of the active complexes such as C4b2b, C3bBb and C5b67

64
Q

soluble C1 inhibitor

A

covalently binds to active C1r2 and C1s2 and dissociates them from C1q, thus stopping activation by the classical pathway

65
Q

membrane-bound decay- accelerating factor

A

displaces Bb from c3bBb or C2b from C4b2b, the alternative and classical pathway c3 convertases

66
Q

soluble anaphylatoxin inactivator

A

proteolytically removes terminal arginine residues and inactivates the anaphylatoxins

67
Q

fluid phase Factor I

A

cleaves cell-associated C3b and C4b. C3b is cleaved to yield iC3b, C3c, C3d, C3f, and C3dg. this factor is active only in the presence of regulatory proteins or cofactors

68
Q

soluble factor H

A

cofactor for cleavage of C3b by factor I

69
Q

s protein

A

binds to C5b67 complex, preventing the complex from inserting into cell membranes

70
Q

Cd59

A

formation of the MAC is inhibited by a widely distributed cell membrane protein on normal host cells called CD59. this works by binding to C5b678 on the cell surface and preventing C9 olymerization

Immunology (a) (6 decks)

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