Chapter-6 Flashcards

1
Q

BC history

A
  1. Repertoire assembly
  2. Neg selec
  3. Pos selec
  4. Searching for infection
  5. Finding infection
  6. Attacking infec
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2
Q

BC development

A
  1. Stem cell- BM of fetal liver
  2. Early pro- DJ rearrangement
  3. late pro- v-DJ arrangement
  4. Late PRE
  5. Large pRE
  6. Small Pre
  7. Immature B cell
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3
Q

BC development

A

BM storms necessary enviro for be cel devel. Secreted products and coadhesion molecules

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4
Q

VCAM-1

A

Binds to VLA-4 integrin on early BC progenitor

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5
Q

IL-7

A

Cytokine important role of

Late pro and late Pre

Stimulate growth and cell division

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6
Q

Ck pts of BC devel

A

I- VDJ rearrangement gives rise to a functional Pre BC

So then the step before -the late pro BC will be permitted to survive and undergo clinal proliferation

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7
Q

Ck pt 2 in BC dev

A

Production of LT chain results in a function surface imm and surviva and maturation Of BC

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8
Q

Large Pre B

A

VDJ rearranged

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9
Q

Late pro b

A

V-DJ is undergoing re arrangement

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10
Q

Early pro b

A

D-J rearrangement

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11
Q

Large Pre b

A

Heavy chain

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12
Q

Small Pre b

A

Light chain

V-J rearranging

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13
Q

Immature BC

A

Functional light chain either lambda or kappa

U heavy chain
IgM on surface

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14
Q

After production of heavy chain as a Pre bC (uVDJ)

A

RAG is degraded
The chromatin struc of heavy chain is reorganized to prevent gene rearrangement
There is allelic exclusion of a second heavy chain

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15
Q

Centrocytes

A

Somatic hyper mutation has occurred

Isotype switching is complete

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16
Q

Neg selection

A

Neg selec ensures that auto reactive BC are prohibited from emerging in the body

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17
Q

B cell repertoire is called

A

Central tolerance when it develops In primary lymphoid organ

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18
Q

Peripheral tolerance

A

When BC is induced outside the BM

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19
Q

Plasma cell

A

Differentiates in the medulla and BM

Produces secreted imm instead of the membrane bound form

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20
Q

What is the surrogate light chain I the PRe-BCR ?

A

VpreB and lambada 5

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21
Q

Pax 5 is analogues to what in the TCD?

A

Notch 1

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22
Q

What is not possible in Ig heavy chains?

A

The same attempt in TCD where’re thymocytes can make four attempts to rearrange a b chain this is because in the Ig there is:

Deletion of all non rearranged D segments

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23
Q

In BCD how many attempts does the heavy chain have to rearrange?

A

Only one attempt of VDJ

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24
Q

BCR summ

A
Controlled by several genes
Somatic recom -Rag
Junctional diversity
Heavy chain-VDJ first 
only tries rearrangement twice one on p and one on maternal
H chain plus surrogate light chain
Apop or success
Cell replication if successful
Light chain -VJ
Tries 4x 
IgM receptor
Apop or success
Cell rep if success
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25
Q

Are BC long or short lived?

A

Are short lived and replenish from immature precursors derived from the BM

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26
Q

What do both B and T cells express?

A

L-selectin

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27
Q

What is pro BC?

A

Earliest ID cell of BC lineage

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28
Q

Early pro b does what?

A

D-j rearrangement

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29
Q

Late pro b rearranges what ?

A

V-DJ

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30
Q

BM stromal cell func

A

Cell- cell contact

  • VCAM
  • SCF to Kit

Secretion of growth factors IL-7

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31
Q

Why can heavy chain locus be inefficient?

A

Complications through adding of N + P

Alters reading frame

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32
Q

Rearrangement of heavy chain has what efficiency?

A

D-J arrangement

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33
Q

V-DJ is less ….

A

Efficient only 50% will make func heavy chain

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34
Q

What does BC need for rearrangement ?

A

Rag 1&2

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35
Q

BC dev needs upreggulation due to what?

A

TF = E2A , EBF

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36
Q

If heavy chain is successful then what does that lead to?

A

U heavy chain

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37
Q

After pro BC then what is next?

A

Pre BC

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38
Q

Pre BC has what two cells?

A

Large Pre BC

Small Pre BC

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39
Q

How do we test the surrogate light chain that will be able to combine with light chain?

A

VpreB

Lamda 5

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40
Q

What is the surrogate light chain controlled by?

A

TF developed in the BM= E2A, EBF

From formation of Pre BC receptor?

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41
Q

Does Pre BC receptor appear on cell surface yet?

A

No pt of membrane enclosed vesicle

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42
Q

The formation of Pre b receptor signals what

A

Pro b to become Pre b

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43
Q

If no Ig a:b cell devel does not what

A

Progress beyond the progenitor sages

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44
Q

What if lambda 5 def?

A

Severe BC deficiency
Persistent bacterial infections

Lambda 5 is apart of the surrogate light chain makes Pre B cell receptor unfunctional

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45
Q

Once u chain is assembled the what?

A

Stops transcription of Rag

Degradation of RAG
Chromatin condensation

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46
Q

Rag is off in BC when..

A

We have u chain

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47
Q

Rag is off when we have

A

B chain in the TC

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48
Q

Large Pre b has what

A

100 small Pre B cell clones
Identical u chain
No longer makes surrogate light chain

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49
Q

Large Pre B cell makes what

A

Light chain
several attempts of VJ
85% of Pre make successful rearrangement

50
Q

What does large Pre b not make?

A

Surrogate light chain

51
Q

What does functional light chain form with

A

Assembles with u chain in Er to form IgM

52
Q

What is a mature BCR

A

Immature BC

53
Q

What occurs in small Pre b?

A

Light chain rearrangement

54
Q

What is clonal expansion?

A

One successful heavy chain gene rearrangement leads up to 85 clones of immature bc

55
Q

What are the two ck pts in BC

A

1st= late pro, Pre b receptor= heavy chain

2nd= small Pre b=func light chain

56
Q

What proteins are involved in BC development

A

TF
GF
Signal transduction
Differentiation markers

57
Q

Where is Tdt found active at

A

Heavy chains

58
Q

What is func of Tdt

A

Insert N + P

59
Q

Tdt is only present in

A

Lymphocytes

60
Q

Proteins involved in BC development

A

Tdt

Iga:b until an effector cell

61
Q

TF of BC development

A

E2A
EBF
Pax5

62
Q

PAx 5

A

The guardian of BC identity and function

63
Q

Pax 5 is import for the

A

Commitment of progenitor cell to b lymphocyte

64
Q

What does pax 5 facilitate

A

Pre B cell receptor

65
Q

What does pax 5 induce

A

V-DJ recombination

66
Q

What does pax 5 encode

A

BSAP

67
Q

What cells are pax 5 in

A

In all cells

68
Q

Pax 5 binds to what in early pro b

A

Enhancer sequence 3’ heavy chain c region

69
Q

What does pax 5 open up

A

Chromatin acess to TF= rag

70
Q

Wht does b1 express

A

Cd5

71
Q

What is cd5

A

Glycoproteins marker of TC lineage

72
Q

B1 cells have no _____Ig

A

IgD

73
Q

B1 cells have what ____ig

A

High affinity for igM

74
Q

B2 cells have ____Ig

A

Low affinity of igM

75
Q

What cytokines does b1 depend on

A

IL-10

76
Q

What can B1 serve as?

A

APC

77
Q

What body cavities does B1 defend against

A

Peritoneal , plural cavities

78
Q

B1 cells are not produced by what_____

A

BM =B2

79
Q

When so we need receptor editing

A

If new BCR doesn’t react with self antigen

80
Q

If we have BCR and reacts with self antigen then what happens

A

Receptor editing - light chain gene rearrangement

81
Q

Why r there mult v-J segments?

A

Because kappa light chain genes have mult segments

82
Q

Clonal deletion

A

Selective death of developing lymphocytes and removal of self reactive receptor

83
Q

What is anergy

A

Inactive and un responsive

84
Q

What do anergic cells make

A

IgD & IgM

85
Q

Anergic has what type of regulation

A

Down reg of surface igM expression

86
Q

After BC leaves BM what is expressed on surface

A

High levels if IgM low IgD

Not fully mature

87
Q

The final stage of BC develop is where

A

Secondary lymphoid tiss

88
Q

Homing is for what

A

Migration of BC to secondary lymphoid

89
Q

Summary of self reactive BC

A

Receptor editing
Die by apop
Become anergic

90
Q

Central tolerance

A

Tolerance in primary lymphoid organ

91
Q

Peripheral tolerance

A

Apop
Anergy

Kicked out of bone marrow

92
Q

CCL21 is secreted by

A

Stromal cells & DC

93
Q

What is the BCR for CCL21

A

CCR7

94
Q

What is CCL19 secreted by

A

DC

95
Q

Homing in BC are mediated via

A

CCL21&19

96
Q

FDC is not a

A

APC

97
Q

What does FDC secrete for homing BC to secondary lymph tiss

A

CXCL13

98
Q

What does CXCL13 attract

A

B cell to follicular DC=FDC

And binds to CXCR5

99
Q

What preserves integrity of FDC

A

LT=lymphotoxin

100
Q

W is LT=lymphotoxin

A

Surface protein on BC

Binds to receptor on FDC

101
Q

W is maturation of BC

A

In 2 lymph

102
Q

BAFF

A

BC activation factor

103
Q

What does BAFF do

A

Promotes BC survival
Bound by baff receptor
Produced by several cell types

104
Q

If no antigen then what

A

BC detached from FDC
Leaves lymph via efferent
Mature naive BC

105
Q

W d immature BC compete with

A

Mature BC for acess to FDC

106
Q

If no acess to FDC then what happens to BC

A

Death
Favors mature BC
1/2 life of mature BC 100 d if not activated

107
Q

What does the mature naive BC diff into

A

Centrolblasts

108
Q

Dark zone is where

A

Germinal center

109
Q

What happens in germinal center

A

Called dark zone b/c somatic hyper mutation =BC proliferation

110
Q

Then what do centroblasts diff into

A

Centrocytes

111
Q

Centrocytes migrate w

A

Into light area

112
Q

Into light area by w

A

Chemokine:

Helper TC
FDC

113
Q

W is T of centrocytes

A

Somatic hypermutatio

Isotype switching is complete

114
Q

What does FDC present

A

Present antigen on surface

Compete for survival

115
Q

W r fates of centrocytes

A

Apop
Class switching
Plasma cell
Memory cell

116
Q

W do plasma cell migrate

A

To medullary cords in lymph

Red pulp in spleen

Laminate propia in gut

BM

117
Q

Memory cells do w

A

Recirculate for long peroid

Require some stim from FDC

Are predom igG

118
Q

What Ig is memory BC

A

IgG had already undergone class switching

119
Q

Explain briefly how movement if BC into LN

A

Entry via HEV through afferent vessel

Migrated into a follicle : CCCR5 -CXCL13

Migrates thru FDC
The. Is yes or n for antigen encounter

120
Q

Migrates thru FDC

Then Is yes _____

A

Travels through the TC zone in germinal center to make then a centrocytes which can have various fates

121
Q

n for antigen encounter _____

A

The cell exits via efferent vessel