Chapter 2: complement Flashcards

1
Q

Complement is what type of proteins?

A

Soluble proteins

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2
Q

Complement is made by what?

A

Liver

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3
Q

Where is complement present?

A

In blood, lymph and extracellular fluids

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4
Q

Many Complement components are what that circulate in functionally inactive forms?

A

proteases or proteolytic enzymes

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5
Q

Inactive form of complement proteins are what?

A

zymogens

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6
Q

What triggers activation of complement?

A

Infection

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7
Q

What do complement do to promote phagocytosis?

A

coat the surface of bacteria and extracellular viruses that makes them more easily phagocytosed.

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8
Q

Complement system is made up of how many proteins?

A

30+

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9
Q

Why is component C3 most important complement protein?

A

Individuals lacking any other complement protein than C3 has no immunodeficiency observed however individuals who lack C3 are susceptible to severe infections

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10
Q

What is complement fixation?

A

Some of the C3b fragment becomes covalently bound to the pathogen’s surface; The C3b becomes firmly fixed to the pathogen.

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11
Q

When C3b becomes covalently bound to a pathogen this is called what?

A

complement fixation.

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12
Q

The bound C3b tags pathogen for what?

A

destrution via phagocytosis and can organize the formation of protein complexes that damage the membrane of the pathogen.

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13
Q

What does C3a do?

A

act as a chemoattractant to recruit effector cells, including phagocytes, from the blood to site of infection.

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14
Q

C3 is cleaved into what?

A

a small C3a fragment and a large C3b fragment

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15
Q

when is the innate immunity brought into play?

A

As soon as a pathogen penetrates an epithelial barrier and starts to live in a human tissue.

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16
Q

Plasma proteins made by the liver are collectively known as what?

A

complement system or just complement

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17
Q

Without complement coating of many bacteria what happens?

A

many bacteria resist phagoctosis, especially those that are enclosed in thick polysaccharide capsules.

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18
Q

What occurs when inactive forms of complement (zymogens) are activated?

A

a series of enzymatic reactions in which each protease cleaves and activates the next protease in the pathway.

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19
Q

Each enzyme is highly specific for the complement component it does what?

A

for the complement component it cleaves and cleavage is usually at a single site.

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20
Q

Most of the enzymes involved in complement belong to what?

A

a large family of serine protease which also includes the digestive enzymes chymotrypsin and trypsin.

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21
Q

C3 has what within the glycoprotein?

A

high-energy thioester bond within the glycoprotein.

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22
Q

How is C3 made and enters circulation?

A

in an inactive form

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23
Q

What is the inactive form of C3?

A

The thioester is sequestered and stabilized within the hydrophobic interior of the protein.

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24
Q

What happens to the thioester bond when C3 is cleaved into small C3a fragment and large c3b fragment?

A

The bond is exposed and becomes subject to nucleophilic attack by water molecules or by the amino and hydroxyl groups of proteins and carbohydrates on the pathogen surface.

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25
Q

The thioester bond being exposed and subject to nucelophilic attack is the result of what?

A

result in some of the C3b becoming covalently bonded to the pathogen. The thioester bonds of the vast majority of C3b molecules are attacked by water and so most of C3b remains in solution in an inactive hydrolyzed form.

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26
Q

Nucleophilic attack by water on the thioester bond on the pathogen surface causes what type of C3b?

A

Soluble C3b that remains in solution in inactive form; majority C3b will be hydrolyzed by water

27
Q

Nucelophilic attack by amino (R-NH2) and hydroxyl groups (R-OH) on thioester bonds on the pathogen surface causes what type of C3b?

A

The C3b becomes covalently bonded to the pathogen surface; only a minority of C3b will be attacked by amino and hydroxyl groups.

28
Q

Protein is hydrophobic and does what to thioester bond?

A

Sequesters and stabilizes the thioester bond

29
Q

What are the three different complement pathways?

A

1) Alternative pathway
2) Lectin pathway
3) Classical pathway

30
Q

How are all three complement pathways alike?

A

They all lead to C3 activation

31
Q

What two complement pathways are part of the innate immune system?

A

1) Alternative pathway

2) Lectin pathway

32
Q

What complement pathway is part of the adaptive immune response as well as the innate immune response?

A

Classical pathway

33
Q

What complement system is the first to act, works at start of infection?

A

Alternative pathway of complement activation

34
Q

What is the second complement system to act?

A

The Lectin pathway which is induced by infection and requires some time before it gains strength.

35
Q

The classical pathway of complement activation requires what?

A

the binding of either antibody or innate immune system protein called C-reactive proteins to the pathogen’s surface.

36
Q

in the alternative complementary pathway the C3 made in the liver is secreted in the blood in inactive form. At a slow rate and without being cleaved C3 does what?

A

Spontaneously changes its conformation and exposes the thioester bond.

37
Q

in the alternative pathway after the thioester bond is exposed what happens?

A

In the aqueous environment of the blood, the thioester bond becomes active and quickly makes a covalent bond that attaches C3 to another molecule that either has an amino or a hydroxyl group

38
Q

In the alternative pathway the C3 becomes active and creates a covalent bond that attaches C3 to another molecule that either has an amino or hydroxyl group. what is usually involved in this process? what is the result?

A

A water molecule is usually involved because they are plentiful. This gives a form of C3 called iC3 or C3(H₂O). This hydrolysis is the first step in the alternative pathway of complement activation.

39
Q

Hydrolysis of C3 in the alternative pathway leads to what?

A

iC3 or C3(H₂O)

40
Q

what facilitates the hydrolyzes of C3 into iC3 djring the alternative pathway?

A

a) environment near the surface of certain pathogens increase rate C3 is hydrolyzed
b) High concentration of C3 in blood also facilitates rpoduction of iC3

41
Q

In the alternative pathway iC3 binds to what?

A

inactive complement factor B

42
Q

iC3 binding to the inactive complement factor B makes factor B what?

A

Susceptible to cleavage by protease factor D

43
Q

factor B cleaved by protease factor D produces what?

A

a small fragemnt Ba which is released and a large fragment Bb

44
Q

The large fragment Bb does what?

A

has protease activity that specifically remains bound to iC3.

45
Q

The iC3bBb complex is what?

A

a soluble convertase protease that specifically and efficiently cleaves C3 into the C3a and C3b fragments. with exppsure of the thioester bond that is in C3b.

46
Q

with large numbers of C3 molecules being cleaved and activated some C3b fragments become what?

A

covalently attached to amino and hydroxyl groups of the pathogen’s outer surface.

47
Q

what are C3 convertases?

A

proteases that cleave and activate C3.

48
Q

iC3Bb is an example of what?

A

soluble C3 convertase

49
Q

Like iC3 pathogen-bound C3b binds what?

A

binds factor B and facilitates the cleavage of factor B by factor D.

50
Q

The binding of factor B to pathogen-bound C3b cleaving factor B by factor D leads to what?

A

to the release of Ba and the formation of a C3bBb complex on the microbial surface.

51
Q

C3bBb is what?

A

a potent convertase called the alternative C3 convertase

52
Q

C3bBb works where?

A

at the surface of the pathogen.

53
Q

C3bBb does what?

A

binds C3 and cleaves it into C3a and C3b with activation of thioester bond

54
Q

the alternative C3 convertase is situated at the pathogen’s surface and is unable to do what?

A

unable to diffuse away like iC3Bb so a larger proportion of the C3b fragments it produces become fixed to the pathogen.

55
Q

Once some C3 convertase molecules have been assembled they do what?

A

they cleave more C3 and fix more C3b at the microbial surface, leading to the assembly of yet more convertase

56
Q

The assembled C3 convertase molecule cleaves more C3 and fixes more C3b at the microbial surface leading to the assembly of yet more convertase is an example of what?

A

Positive feed back

57
Q

The positive-feedback process in which C3b product of the enzymatic reaction can assemble more enzyme is what?

A

one of the progressive amplificatiom of C3 clevage.

58
Q

What is the ultimate outcome once the initia’ deposition of a few molecules of C3b?

A

pathogen rapidly coated with C3b

59
Q

Two broad categories of complement control proteins regulate what?

A

regulating rapid and runaway reactions like those of alternative C3 convertase.

60
Q

How do complement control proteins regulate rapid runaway reactions?

A

mainly by stabilizing or degrading C3b at cell surfaces.

61
Q

What are the two broad categories of complement control proteins?

A

1) plasma proteins that interact with C3b attached to human and microbial cell surfaces
2) Membrane proteins on human cells that prevent complement fixation at the cell surface.

62
Q

The plasma control proteins are called what?

A

protein properdin (factor p), protein factor H and protein factor I.

63
Q

What does Properdin (factor P) do?

A

increases the speed and power of complement activation by binding to the C3 convertase C3bBb on microbial surfaces and preventing its degradation by proteases.

64
Q

What counters the effect of Properdin?

A

plasma protein factor H.