Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Module 3 > B cell tolerance > Flashcards

B cell tolerance Flashcards

1
Q

How are peripheral T cell numbers maintained in mature individuals?

A

division of mature T cells outside the central lymmphoid organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is positive selection particularly important for a:b T cells?

A

ensures that an individuals T cells will be able to respond to peptides bound to one’s own MHC molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the default fate of developing lymphocytes, in the absence of any signal being received from the receptor?

A

death by apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which cells in the bone marrow provide the signals for the differentiation of haematopoietic stem cells?

A

specialised nonlymphoid connective tissue stromal cells that are in intimate contact with the developing lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 2 functions of the stromal cells in the bone marrow?

A

form specific adhesive contacts with the developing lymphocytes by interactions between cell-adhesion molecules and their ligands; provide soluble and membrane cytokines and chemokines that control lymphocyte differentiation and prolfieration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do HSCs first differentiate into?

A

multipotent progenitor cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the difference between HSCs and MPCs?

A

aren’t self renewing stem cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What cell surface receptor do MPPs have that binds to stromal cells?

A

FLT3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Give examples of transcription factors that MPPs possess that are required for the development of multiple haematopoietic lineages?

A

PU.1 and c-kit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does differentation of the MPPs into the common lymphoid progenitor require?

A

signalling through the FLT3 receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What 2 subsets of progenitor cell does the MPP produce that gives rise to all lymphocytes?

A

one unnamed- produces the ILC subsets and the common lymphoid progenitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do B-cell committed CLPs give rise to?

A

pro-B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Expression of what receptor accompanies the production of lymphocyte progenitors from the multipotent progenitor cell?

A

IL-7 receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What induces the IL7 receptor expression?

A

FLT3 signalling and PU.1 activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What 2 polypeptides make up the IL-7 receptor?

A

IL-7 receptor alpha chain and the common cytokine receptor y chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What tyrosine kinase do all cytokine receptors with the common cytokine receptor y chain share?

A

Jak3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What membrane bound cytokine present on bone marrow stromal cells is required f or the growth of HSCs and earliest B-lineage cells?

A

stem cell factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What receptor does stem cell factor interact with?

A

Kit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What chemokine is required fro the early stages of B cell devleopment?

A

CXCL12 (stromal cell-derived factor 1 SDF-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is one of the roles of CXCL12?

A

reatin developing B cell precursors in the marrow microenvironment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is hte pro-B cell defined by?

A

induction of the B lineage specific transcription factor E2A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does E2A expression induce?

A

early B cell factor EBF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the function of E2A and EBF?

A

drive the expression of proteins that determine the pro-B cell state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where do the earliest stem cells reside in the bone marrow?

A

endosteum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How do B cells migrate as they develop?

A

towards the central sinus of the marrow cavity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the stages of B cell development in order?

A

early pro-B cell; late pro-B cell; large pre-B cell; small pre-B cell; immature B cell; mature B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Where does development from an immature to mature B cell occur?

A

peripheral lymphoid organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How is rearrangement of the heavy-chain locus initiated ?

A

E2A and EBF induce Rag-1 and Rag-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

When does D to J rearrangement occur?

A

mainly in the early pro-B cell stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the function of Pax5?

A

targets the genes for CD19 and the gene for Iga ; induces expression of B-cell linker protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How is Pax5 induced?

A

E2A and EBF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What indicates that Pax5 is required for commitment of the pro-B cell to the B cell lineage?

A

without Pax5 cells cannot develop further down the B cell lineage but can be induced to give rise to T cells and the myeloid lineage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the function of B-cell linker protein?

A

its a scaffold protein that is required for further devleopment of the pro-B cell and for signalling from the mature B cell antigen receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

When does V-DJ rearrangement occur?

A

late pro-B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What defines the large pre-B cell?

A

expression of the complete immunoglobulin heavy chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How does the large pre-B cell become a small pre-B cell?

A

by proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is seen in the small pre-B cell?

A

express the mu heavy chain alone in the cytoplasm as no longer express the surrogate light chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the surrogate light chains?

A

lamda5 and VpreB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What happens once a B cell has successfully expressed a light chain gene?

A

immature B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is seen on the surface of a mature B cell?

A

both mu and delta heavy chain expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are the earliest B-lineage surface markers?

A

CD19 and CD45R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What surface markers distinguish the pro-B cells?

A

CD43; Kit and IL-7R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What surface marker does the late pro-B cell start to express?

A

CD24

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What surface markers is a pre-B cell distinguished by?

A

enzyme BP-1, Kit is no longer expressed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

When does V to DJ rearrangement occur on both chromosomes?

A

if V to DJ rearrangement does not produce a functional H chain on the first chromsome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What makes up the pre-B cell receptor?

A

H chain with VpreB and lambda5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What associates with the pre-B cell receptor?

A

Iga and Igb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What does association of the pre-B cell receptor with the Iga and Igb chains do?

A

tells the cell to stop H rearrangement and undergo proliferation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Which type of light chain rearrangement occurs first?

A

kappa light chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is the difference between D to J rearrangement and DJ to V rearrangemetn?

A

D to J occurs on both chromosomes whereas DJ to V rearrangement occurs first on only one

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

When is TdT expressed in B cell development?

A

pro-B cell stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Why are there less N-nucleotides seen in light cahins?

A

expression of TdT declines at the pre-B cell stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is the checkpoint that mediates the transition betwen the pro-B cell and pre-B cell?

A

formation of the pre-B cell receptor and signalling through it

54
Q

How are the signals required for transition through the chekpoint created by the pre-B cell receptor?

A

form dimers or oligomers that generate signals

55
Q

What downstream signalling molecules are required for signalling through the pre-B cell receptor?

A

BLNK and Btk

56
Q

What allows the pro-B cell to become sensitive to IL-7?

A

signallling generated by the pre-B cell receptor stops further rearrangement of the heavy chain locus—sensitivity induces prolfieration

57
Q

How does the pre-B cell receptor prevent a B cell from producing 2 receptors of different antigen specificites?

A

enforces allelic exclusion

58
Q

How does the pre-B cell receptor enforce allelic exclusion?

A

reduces the expression of Rag1 and Rag2; causes Rag2 to be targeted for degradation; reduces access of the heavy chain locus to the recombinase machinery

59
Q

How are many cells with different antigen specificites created from one pre-B cell?

A

after proliferation, all the cells undergo light chain rearrangements

60
Q

How can several attempts at recombination of a light chain gene be made on one chromosome?

A

repeated rearrangements of unused V and J segments can occur

61
Q

How is the k:l ratio in mature lymphocyte populations useful in clinical diagnostics?

A

an aberrant ratio indicates the dominance of once clone and the presence of a lymphoproliferative disorder

62
Q

What is release of immature B cells from the bone marrow dependent on?

A

expression of S1PR1

63
Q

How do B cells leave the marrow?

A

through sinusoids

64
Q

What happens if the BCR encounters a strongly cross-linking antigen in the bone marrow?

A

development is arrested

65
Q

What are the 4 possible fates of a self-reactive BCR?

A

receptor editing; cell death by apoptosis restuling in clonal deletion; anergy; immmunological ignorance

66
Q

What determines the fate of a self-reactive BCR?

A

the interaction of the BCR with the self-antigen

67
Q

What causes a B cell to undergo receptor editing?

A

if recognises a multivalent self antigen

68
Q

What happens in receptor editing?

A

replacement of the light chain until a nonself reactive receptor is produced or there are no additional light chain V and J segments avaialable

69
Q

What happens to immature B cells that encounter more weakly cross-linking self antigens of low valence such as small soluble proteins?

A

anergy

70
Q

Where are anergic B cells detained?

A

T cell areas of peripheral lymphoid tissues and cannot access lymphoid follicles

71
Q

Why should immunologically ignorant B cells be considered inert?

A

they can be activated when there is lots of inflammation or when self-antigen reaches high concentration

72
Q

What would happen is the elimination of self-reactive cells was too efficient?

A

receptor repertoire might become too limited

73
Q

Why are not all autoreactive B cells purged in the bone marrow?

A

only lyphocytes specific for autoantigens that are expressed in or can reach the bone marrow are affected

74
Q

Why do B cells only become fully mature in the periphery?

A

provides an opportunity for immature B cells to encounter peripheral self antigen and undergo tolerance

75
Q

How does the expression of sIgM and sIgD change between immature and mature B cells ?

A

immature have more sIgM than sIgD whereas for mature it is the opposite

76
Q

Which cells produce BAFF most abundantly?

A

follicular Dcs

77
Q

What are follicular DCs?

A

non-haematopoieitc cells resident in B cell follicles specialised to capture antigens for recognition by B cell receptors

78
Q

What are the 3 receptors for BAFF?

A

BAFF-R; BCMA; TACI

79
Q

What is the difference between BAFF-R and BMCA/TACI?

A

BMCA and TACI also respond to APRIL

80
Q

What is important about APRIL?

A

IgA production

81
Q

What 2 transitional stages do immature B cells in the spleen proceed through?

A

T1 and T2

82
Q

What are T1 and T2 defined by>

A

the absence/presence of CD21

83
Q

What happens to mice lacking BAFF?

A

cannot acquire CD21 and progress to T2

84
Q

What is required to promote the final stages of B cell maturation in the periphery?

A

weak BCR signals and BAFF

85
Q

What disease is linked to overexpression of BAFF?

A

Sjogrens

86
Q

How can marginal B cells be identified?

A

very high levels of CD21 expression

87
Q

What is a major determinant of whether a B cell will be follicluar or marginal zone?

A

the specificity of the BCR

88
Q

What is the function of marginal zone B cells?

A

poised to make rapid responses to antigens or pathogens filtered from the blood- early line of defense for blood borne pathogens

89
Q

What is expressed by fDCs to attract B cells to the follicles?

A

CXCL13 (binds to CXCR5)

90
Q

What happens to mice lacking Syk and what does this indicate about its function in maturation?

A

have immature B cells but not mature B cells therefore a Syk-transduced signal from the BCR must be required for full B cell maturation

91
Q

What indicates that continuous BCR expression is required for B cell survival?

A

clonal deletion of BCRs in mature B cells results in loss of all mature B cells

92
Q

What part of the immune system are B-1 B cells part of

A

innate immune system

93
Q

Where are B-1 B cells found in high numbers?

A

peritoneal and pleural cavities

94
Q

What is the function of B1 B cells?

A

major source of natural antibodies- those constitutively produced circulating antibodies secreted prior to infection

95
Q

What do most antibodies made by B-1 B cells recognsie?

A

capsular polysaccharide

96
Q

What is one important feature of B-1 B cells?

A

can produce IgM antibodies wihtou help from T cells; although response can be enhacned by cooperation

97
Q

What are most B-1 B cells derived from?

A

progenitor cells found in the fetal liver

98
Q

How are B-1 cells renewed?

A

self-renewal

99
Q

What is the difference between the dependence on other signals in B-1 cells and B-2 cells ?

A

B-1 cells do not need BAFF or IL-7

100
Q

What is a difference between immune tolerance and immunosuppression?

A

immune tolerance is antigen specific whereas immunosuppression is non-ag specific

101
Q

What is immunosuppression?

A

when an appropriate immune response does not happen resulting in harm to the organsim- infection or tumour

102
Q

What is the deletion in scurfy mice?

A

deletion in the forkhead domain of FOXP3

103
Q

How long does it take scurfy mice to die?

A

3-5 weeks

104
Q

What does FOXP3 stand for?

A

forkhead box protein 3 gene

105
Q

What is the only treatment for IPEX

A

bone marrow transplantation

106
Q

What is CLP Pax5 expressing cell?

A

committed B cell precursor

107
Q

Which B cells undergo VJ joining of the light chain locus?

A

small pre-B cells

108
Q

When do B cells start to express CD45?

A

early pro-B cell

109
Q

What cytokine is required for a cell to become a large pre-B cell?

A

IL7

110
Q

When do B cells start to express CD19?

A

late pro-B cell

111
Q

What are marginal zone B cells?

A

non-class switched memory B cells that populate the marginal zone which can differentiate into short lived IgM secreting plasma cells

112
Q

What happens once a B cell has encountered an antigen?

A

naive B cells move from the mantle zone to primary follicle to start a germinal reaction

113
Q

What is the name for B cells in the dark zone?

A

centroblast

114
Q

What are the B cells in the light zone called?

A

centrocyte

115
Q

What are the features of plasma cells?

A

don’t express CD19; CD20; CD40; MHC-II or sIg, can no longer receive T cell help and are incapable of cell division

116
Q

What happens to B cells that encounter self antigens in peripheral lymphoid tissue?

A

anergy if mature or Fas mediated apoptosis if transitional

117
Q

What are the features of anergic B cells?

A

downregulate Cd21; express high levels of inhibitory receptors; downregulate lymph node homing CCR7 so leave follicle and die

118
Q

What first identified the regultory potential of B cells?

A

transfer of splenocytes lacking B cells failed to prevent T cell induced delayed-type skin hypersensitivity, but if give splenocytes from a mouse already exposed to the antigen, don;t develop

119
Q

Prpduction of what cytokine is linked to the regulatory function of B cells?

A

IL-10

120
Q

What is the mouse model for Bregs?

A

no Breg deficient mouse model analogous to Scurfy

121
Q

What is the phenotype for Bregs?

A

no single conclusive phenotype and no transcription factor analogous to FOXP3 foudn

122
Q

What are other potential mechanisms by which B cells induce toelrance?

A

TGFb; IL-12; IL4; FasL expression

123
Q

How can Breg function be induced?

A

with CD40L and CPG and IL-1b and IL-6

124
Q

What do the factors that induce Breg function suggest about when they arise?

A

that they arise in the inflammatory site

125
Q

What is the function of Breg?

A

suppress activated T cells and monocytes proliferation/cytokine secretion; induce Treg differentation

126
Q

What are Tr1 cells?

A

IL-10+ regulatory T cells

127
Q

How do Bregs carry out their functions?

A

IL-10 dependent; cellular contact is required

128
Q

What diseases have been linked to decreased numbers and function of Bregs?

A

MS; ITP; SLe; RA

129
Q

What are the risks with the therapeutic potential of immune regulation?

A

non-specific immune suppression- infection; tumours; autoimmunity; conversion to pathogenic cells

130
Q

What diseases have ongoing trials into the use of Tregs as therapeticsc?

A

GvHD; transplantation and some autoimmune disorders

131
Q

Why is it difficult to identify Bregs for studying them?

A

in order to stain for IL-10 you have to kill the cell

Module 3 (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions