the complement system

Question 0

complement proteins are normally found in

Answer 0

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

Question 1

complement system

Answer 1

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

Question 2

complement proteins are synthesized by the

Answer 2

liver and macrophages

Question 3

Juleus Bordet concluded that the lytic effect required two factors:

Answer 3

1) specific antibody

2) heat- liable component present in normal serum

Question 4

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

Answer 4

complement

Question 5

two main pathways for complement activation:

Answer 5

1) classical way

2) alternative pathway

Question 6

classical pathway is initiated by:

Answer 6

antigen-antibody (IgM or IgG) complexes

Question 7

alternative pathway is initiated by:

Answer 7

microbial surfaces

Question 8

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

Answer 8

C3b, the central molecule of the complement cascade

Question 9

C3B can combine with other complement components to generate

Answer 9

C5 convertase

Question 10

C5 convertase

Answer 10

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

Question 11

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

Answer 11

activated

cell membrane lysis

Question 12

C3 is

Answer 12

the most abundant complement protein

Question 13

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”).

Answer 13

proteolytic cleavage
proenzymes or zymogens
small fragment
major fragment

Question 14

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

Answer 14

inhibit

minimize

Question 15

T or F:

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

Answer 15

T

Question 16

proteins of the classical pathway

Answer 16

C1( C1qr2s2)
C2
C3
C4

Question 17

proteins of the alternative pathway

Answer 17

C3
Factor B
Factor D
Properdin

Question 18

the classical complement pathway

Answer 18

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

Question 19

C1 is composed of 3 subunits:

Answer 19

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

Question 20

C1q

Answer 20

• 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

Question 21

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

Answer 21

one

two

Question 22

T or F:

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

Answer 22

true

Question 23

C1r

Answer 23

• 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

Question 24

C1s

Answer 24

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

Question 25

C4b fragment

Answer 25

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

Question 26

C4a fragment

Answer 26

is released into the fluid phase

Question 27

C2

Answer 27

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

Question 28

classical C3 convertase

Answer 28

C2b remains bound to C4b to form an enzyme complex C4b2b

Question 29

substrate modulation

Answer 29

C1s cannot act on C2 unless it is bound to C4b

Question 30

C3

Answer 30

- activated by proteolytic cleavage | - C4b2b binds to and proteolytically cleaves C3 into C3b and a small C3a fragment

Question 31

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

Answer 31

200 | amplification

Question 32

there are 3 things that C3b can do:

Answer 32

- 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

Question 33

C5 convertase

Answer 33

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

Question 34

C5a

Answer 34

is released into the fluid phase

Question 35

C5b

Answer 35

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

Question 36

alternative complement pathway

Answer 36

-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

Question 37

microbial structure that can activate the alternative pathway include:

Answer 37

lipopolysaccharide teichoic acid zymosan viral envelopes

Question 38

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

Answer 38

more first IgG IgM

Question 39

the thioester bond in C3 can be cleaved by:

Answer 39

plasmin phagocyte proteases trypsin

Question 40

C3b binding to host cell surfaces is inactivated by :

Answer 40

factor H and I

Question 41

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

Answer 41

sialic acid | increase

Question 42

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

Answer 42

inhibit H C3b

Question 43

factor d

Answer 43

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

Question 44

C3bBb

Answer 44

is the alternative C3 convertase and it cleaves more C3 molecules, initiating anamplification sequence for C3b extremely unstable unless bound to properdin

Question 45

C5 convertase

Answer 45

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.

Question 46

C5b67 complex

Answer 46

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

Question 47

C5b678 complex

Answer 47

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

Question 48

complement receptors

Answer 48

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

Question 49

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

Answer 49

proteolytic

Question 50

only cell lysis is mediated by the

Answer 50

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

Question 51

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

Answer 51

Gram positive bacteria

Question 52

chemotactic fragments include:

Answer 52

C5a, C3a, C5b67 | chemotaxis of monocytes/macrophages and polymorphs

Question 53

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

Answer 53

C3b, C4b, iC3b

Question 54

___>___>___ 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.

Answer 54

C5a, C3a, C4a (anaphylatoxins)

Question 55

C5a and C3a

Answer 55

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

Question 56

P-selectin

Answer 56

promotes neutrophil binding

Question 57

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

Answer 57

directly | bronchospasm

Question 58

activation of phagocytes involves:

Answer 58

- 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

Question 59

Bb

Answer 59

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

Question 60

the central role of C3b

Answer 60

- 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

Question 61

Uncontrolled activation of complement can:

Answer 61

- rapidly deplete complement proteins - lead to formation of MAC on normal host cells - result in excessive generation of inflammatory mediators

Question 62

regulation of complement is mediated by:

Answer 62

circulating and cell surface proteins

Question 63

spontaneous decay of activated complement components include:

Answer 63

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

Question 64

soluble C1 inhibitor

Answer 64

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

Question 65

membrane-bound decay- accelerating factor

Answer 65

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

Question 66

soluble anaphylatoxin inactivator

Answer 66

proteolytically removes terminal arginine residues and inactivates the anaphylatoxins

Question 67

fluid phase Factor I

Answer 67

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

Question 68

soluble factor H

Answer 68

cofactor for cleavage of C3b by factor I

Question 69

s protein

Answer 69

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

Question 70

Cd59

Answer 70

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