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Immunology test III > Lecture 17 - Effector Mechanisms of Humoral Immunity > Flashcards

Lecture 17 - Effector Mechanisms of Humoral Immunity Flashcards

1
Q

What are the effector functions of Abs?

A
  1. neutralize these agents
  2. Opsonize them for phragocytosis
  3. Sensitize them for Ab-dependent cellular cytotoxicity
  4. Activate the complement system
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2
Q

Abs are produced by plasma cells where?

A

in primary (bone marrow) and secondary (LNs) lymphoid organs

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3
Q

Abs that mediate protective immunity may be derived from what cells?

A

short or long lived Ab-producing plasma cells

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4
Q

Abs perform effector functions in various tissues distant from what?

A

their production sites

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5
Q

Many of the effector functions of Abs are mediated by what?

A

heavy chain constant region (Fc) of Ig molecules

Different Ig heavy chain isotypes serve distinct effector functions

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6
Q

Ab effector functions are triggered only after what?

A

After Ag binding

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7
Q

Describe vaccine-induced humoral immunity against polio?

A

Oral attenuated poliovirus/ nuetralization of virus by mucosal IgA Ab

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8
Q

Describe vaccine-induced humoral immunity against tetanus, diphteria?

A

Toxoids/ neutralization of toxin by systemic IgG Ab

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9
Q

Describe vaccine-induced humoral immunity against Hep A or B?

A

Recombinant viral envelope proteins/ neutralization of virus by mucosal IgA or systemic IgG Ab

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10
Q

Describe vaccine-induced humoral immunity against pneumococcal pneumonia, haemophilus?

A

Conjugate vaccines composed of bacterial capsular polysaccharide attached to a carrier protein/ opsonization and phagocytosis mediated by IgM and IgG Abs, directly or secondary to complement activation

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11
Q

Abs against microbes and microbial toxins block what?

A

The binding of these microbes and toxins to cellular receptors

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12
Q

How do influenza viruses and gram-negative bacteria attack host cells?

A

Influenza viruses use their envelope hemagglutinin to infect respiratory epithelial cells
Gram-negative bacteria use pili to attach to and infect a variety of host cells

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13
Q

Abs that bind to microbial structures interefere with the ability of the microbes to do what?

A

interact with cellular receptors by means of steric hindrance and may thus prevent infection

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14
Q

What blocks the spread of microbes from an infected cell to an adjacent uninfected cell?

A

Antibodies

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15
Q

What inhibits the pathologic effects of toxins?

A

Antibodies that block the binding of toxins to cells

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16
Q

What antibodies coat microbes and promote their phagocytosis by binding to Fc receptors on phagocytes?

A

IgG

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17
Q

What are the types of Fc receptors?

A
  1. FcγRI - high affinity - phagocytosis, cell activation
  2. FcγRII - low - phago, cell act, feedback inhibition
  3. FcγRIII - low - Ab-dependent cell-mediated cytotoxicity
  4. FceRI - high - cell act
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18
Q

Binding of Fc receptors (FCγRI) on phagocytes to multivalent ab-coated particles leads to what?

A

phagocytosis and the activation of phagocytes

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19
Q

WHat are the most efficient opsonins for promoting phagocytosis via high affinity FcγRI (CD64)?

A

IgG1 and IgG3

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20
Q

Signals from what receptors activate the phagocytes to destroy these opsonized microbes?

A

Fc receptor

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21
Q

Ab of certain IgG subclasses bind to infected host cells and the Fc regions of the bound Ab are recognized by what receptor on NK cells?

A

FcγRIII

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22
Q

NK cells activated by ADCC kill what cells?

A

Ab-coated cells

ADCC = antibody-dependent cell-mediated cytotoxicity

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23
Q

What cells function together to mediate the killing and expulsion of some helminthic parasites?

A

IgE, eosinophils, and mast cells

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24
Q

Worms are too large to be engulfed by phagocytes and they are relatively resistant to what?

A

The microbicidal products of neutrophils and Mo

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25
Q

What can worms be killed by?

A

A toxic cationic protein, known as the major basic protein, present in the granules of eosinophils

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26
Q

What can cause the degranulation of eosinophils, releasing the basic protein and other eosinophil granule contents that kill the parasites?

A

IgE that coat helminths can bind to FCeRI on eosinophils causing these events to happen

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27
Q

What consists of serum and cell surface proteins that interact with one another and with other molecules of the immune system in a highly regulated manner to generate products that function to eliminate microbes?

A

The complement system

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28
Q

What is one of the major effector mechanisms of humoral immunity and is also an important effector mechanism of innate immunity ?

A

Complement system

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29
Q

What is the complement system activated by?

A

microbes and by Abs that are attached to microbes and other antigens

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30
Q

Activation of complement involves the seqential proteolysis of what molecules to generate enzyme complexes with proteolytic activity?

A

proteins

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31
Q

The products of complement activation become covalently attached to what?

A

microbes, Abs bound to microbes, and to other Ags, and to apoptotic bodies

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32
Q

What is complement activation inhibited by?

A

reg proteins that are present on normal host cells and absent from microbes

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33
Q

What are the three pathways of complement activation?

A

classical, alternative and lectin

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34
Q

The complement activation depends on the generation of what two proteolytic complexes?

A

The C3 convertase, which cleaves C3 into two proteolytic fragments called C3a and C3b

C5 convertase, which cleave C5 into C5a and C5b

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35
Q

What is the alternative pathway activated by?

A

C3b binding to various activating surfaces

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36
Q

What is the classical pathway activated by?

A

C1 binding to Ag-Ab complexes

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37
Q

What is the lectin pathway activated by?

A

binding of a plasma lectin to microbes

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38
Q

What steps of all three pathways are the same?

A

The late steps

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39
Q

The proteolytic cleavage of what chain of C3 converts it into a metastable form (alternative)?

A

alpha

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40
Q

Once C3 is in a metastable form, what are exposed and susceptible to nucleophilic attack by oxygen atoms or nitrogen atom? (alternative)

A

Thioester bonds

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41
Q

The exposed thioester bonds of C3b results in the formation of what? (alternative)

A

covalent bonds with proteins or carboydrates on the cell surfaces

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42
Q

What is structually homologous to C3 and has an identical thioester group?

A

C4

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43
Q

Spontaneous hydrolysis of plasma C3 leads to the formation of what? (alternative)

A

fluid-phase C3 convertase and the generation of C3b

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44
Q

If C3b is deposited on the surfaces of microbes, it binds what to form the alternative pathway C3 convertase?

A

Factor B

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45
Q

The C3 convertase cleaves C3 to produce more C3b, which binds to what? (alternative)

A

The microbial surface and participates in the formation of a C5 convertase

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46
Q

The C5 convertase cleaves C5 to genearte C5b, this is the initiating event in what steps of complement activation? (alternative)

A

Late steps

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47
Q

What are the functions of C3b?

A

Binds to the surface, opsonin, and a component of C3 and C5 convertases

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48
Q

What are the functions of C3a?

A

Stimulates inflammation

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49
Q

What are the functions of Bb?

A

A serine protease and the active enzyme of the C3 and C5 convertase

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50
Q

What is the function of factor D?

A

Plasma serine protease cleaves factor B when it is bound to C3b

51
Q

What is the function of properdin?

A

Stabilizes C3 convertases (C3bBb) on microbial surfaces

52
Q

What is the classical pathway initiated by?

A

binding of the C1 to IgG or IgM molecules that are bound to Ag

53
Q

What is C1 composed of? (classical)

A

C1q, C1r, and C1s subunits

54
Q

What does each subunit of C1 do?

A

C1q binds to Ab, while C1r and C1s are proteases

55
Q

C1q consists of how many subunits?

A

six identical subunits arranged as radial arms

56
Q

What are the contact regions for immunoglobulins on C1?

A

The globular heads at the end of each C1q arm, designated H

57
Q

Cr1 and C1s form a tetramer composed of what?

A

two C1r and two C1s molecules

58
Q

The ends of C1r and C1s contain what domains?

A

the catalytic domains of these proteins

59
Q

What must C1 bind to, in order to initiate the complement cascade?

A

To two or more Fc portions

60
Q

After IgM binds to surface-bound Ags, it undergoes what changes in the classical pathway?

A

A shape change that permits C1 binding and activation

61
Q

Will soluable IgG molecules activate C1?

A

No because each IgG has only one Fc region, but after binding to cell surface Ags, adjacent IgG Fc portions can bind and activate C1

62
Q

The classical pathway is initated by the binding of C1 to what molecules?

A

antigen-complexed antibody molecules

63
Q

Activated C1s cleaves what next protein in the cascade?

A

C4, to generate C4b

64
Q

What does C4b contain that forms covalent bonding with microbe to which the Ab is bound? (classical)

A

thioester bond

65
Q

What does the thioester bond ensure?

classical

A

That the classical pathway activation proceeds on a microbial surface

66
Q

What is cleaved by a nearby C1s molecule to generate a fragment of unknown importance and another fragment that remains physically associated with C4b?

A

C2 is cleaved into C2b and C2a (associated with C4b)

67
Q

The resulting C4b2a complex is the classical pathway _________.

A

C3 convertase

68
Q

Cleavage of C3 results in the removal of the small C3a fragment, and C3b can form covalent bonds with what? (classical)

A

Cell surfaces

69
Q

Once C3b is deposited, it can bind what to generate more C3 convertase by the alternative pathway? (classical)

A

Factor B

70
Q

Some of the C3b molecules generated by the classical pathway C3 convertase binds to the convertase and forms what?

A

C4b2a3b complex

Classical pathway C5 convertase - It cleaves C5 and initiates the late steps of complement activation

71
Q

The lectin pathway is triggered by the binding of microbial polysaccharides to what?

A

circulating lectins, such as plasma mannose-binding lectin

72
Q

MBL binds to what residues on bacterial polysaccharides?

A

mannose

73
Q

MBL associates with MBL-associated serine proteases including what MASPs?

A

MASP1, 2, and 3

74
Q

The MASP proteins are structurally homologous to what?

A

C1r and C1s proteases

75
Q

What cleaves C4 and C2 to activate the complement pathway in the lectin pathway?

A

MASP

*subsequent events in this pathway are identical to those that occur in the classical pathway

76
Q

C5 convertases cleaves C5 into what fragments?

A

C5a that is released and C5b that remains bound to the complement proteins deposited on the cell surface

77
Q

What does C5b bind?

A

C6 and C7

78
Q

What component of the C5b, 6, 7 complex is hydrophobic and inserts into the lipid bilayer of cell membranes?

A

C7

79
Q

C7 becomes a high-affinity receptor for what?

A

C8, and then the C5b,6,7,8 complex is formed

80
Q

The formation of a fully active MAC is accomplished by the binding of what?

A

C9

81
Q

C9 polymerizes at the site of the bound C5b-8 to form what?

A

pores in the plasma membranes

82
Q

CR1 promotes phagocytosis of what particles?

A

C3b and C4b-coated particles

83
Q

CR1 promotes clearance of what?

A

Immune complexes from the circulation

84
Q

Phagocytes use what receptor to bind and internalize microbes and debris?

A

CR1

85
Q

CR1 also transduces signals that activate what mechanisms of phagocytes?

A

killing

86
Q

CR2 binds the cleavage products of what?

A

C3b (C3d, C3dg, and iC3b)

87
Q

On B cells, what does CR2 enhance?

A

The responses of B cells to Ag

88
Q

On follicular DC, CR2 does what?

A

traps iC3-coated Ag-Ab complexes in germinal centers

89
Q

What virus enters B cells via CR2 and infects these cells and remain latent in infected cells for life?

A

Epstein-Barr virus

90
Q

What is CR3 also called?

A

Mac-1

91
Q

What is an integrin that functions as a receptor for the iC3b fragment generated by proteolysis of C3b?

A

CR3

92
Q

CR3 is involved in the recruitment of of leukocytes to sites of infection and tissue injury by binding to what?

A

ICAM-1 on endothelial cells

93
Q

What binds to iC3b and the functions of this receptor is probably similar to that of Mac-1?

A

CR4

94
Q

Why must complement activation be regulated?

A

To prevent complement activation on normal host cells and to limit the duration of complement activation even on microbial cells and antigen-antibody complexes

95
Q

What is C1 INH?

A

Sering protease inhibitor that displaces C1r2s2 from C1q and terminates classical activation

96
Q

What is DAF?

A

Decay-accelerating factor: displaces C2a from C4b and Bb from C3b (dissociates C3 convertase)

97
Q

What functions similarly to DAF?

A

MCP and CR1

98
Q

In the presence of what cell membrane-bound cofactors does plasma factor 1 proteolytically cleave C3b attached to cell surfaces?

A

MCP or CR1

*Factor H can also serve as cofactors for factor I-mediated cleavage of C3b

99
Q

What does plasma factor I generates?

A

inactive form of C3b - iC3b

100
Q

What inhibits the formation of MAC?

A

Membrane protein CD59 and S protein in the plasma

101
Q

Microbes on which complement is activated by the alternative or classical pathway become coated with what?

A

C3b, iC3b or C4b, and are phagocytized by the binding of these proteins to specific receptors on macrophages and neutrophils

102
Q

What proteolytic complement fragments induce acute inflammation by activating mast cells, neutrophils and endothelial cells?

A

C4a, C4a, and C3a

103
Q

What protein generated from C3 binds to CR2 on B cells and facilitates B cell activation and the initiation of humoral immune responses?

A

C3d

104
Q

What is the most common human complement deficiency?

A

C2 deficiency

105
Q

What deficiencies develop systemic lupus erythematosus?

A

C1q, C2 and C4

106
Q

Defects in complement activation leads to failure to clear what?

A

Circulating immune complexes

Complexes may be deposited in blood vessel walls and tissues, where they produce local inflammation

107
Q

What deficiencies are not usually associated with increased susceptibility to infections?

A

C2 and C4 - alternate pathway may compensate

108
Q

What is C3 deficiency associated with ?

A

frequent serious pyogenic bacterial infections that may be fatal

109
Q

Deficiencies in what results in increased susceptibility to infection with pyogenic bacteria?

A

properdin and Factor D

110
Q

Deficiencies in C5-C9 may result in what?

A

disseminated infections by Neisseria bacteria

111
Q

Complement system can cause significant ____ damage

A

tissue

112
Q

Some of the pathologic effects associated with bacterial infections may be due to complement-mediated _____ ______ responses to infectious organizations.

A

Acute inflammatory

113
Q

Complement activation is associated with _______ ________ and can lead to ischemic injury to tissues

A

Intravascular thrombosis

114
Q

In an autoantibody-mediated kidney disorder, membranous nephropathy, damage to glomerular epithelial cells can be mediated by what?

A

The MAC that is generated after Ab binds to a glomerular auto-Ag

115
Q

How can microbes evade the complement system?

A

By recruiting host complement regulatory proteins

116
Q

Many pathogens express _____ that can inhibit the alternative pathway of complement by recruiting Factor H - which displaces C3b from Bb

A

Sialic acids

117
Q

Many other pathogens have evolved proteins that facilitate the recruitment of what?

A

Factor H to their cell walls

118
Q

HIV incorporates multiple host reg proteins into their envelopes. Name specifics

A

GPI-anchored complement reg proteins DAF and CD59 when it buds from an infected cell

119
Q

Abs in ingested milk transport across what epithelium of newborns?

A

The gut

120
Q

How do Abs transport across the gut epithelium?

A

Process known as transcytosis

121
Q

Transport of maternal IgG across the placenta and across the neonatal intestinal epithelium is mediated by what?

A

An IgG-specific Fc receptor called the neonatal Fc receptor (FcRn)

122
Q

Maternal IgG is transported across what?

A

placenta

123
Q

Maternal IgA and IgG are given to an infant how?

A

In breast milk

124
Q

Ingested IgA and IgG can neutralize pathogenic organisms that attempt to do what?

A

colonize in infant’s gut

Immunology test III (7 decks)

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