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Immunology > [EXAM 2] Lecture 4 (Development of B cells and T cells) > Flashcards

[EXAM 2] Lecture 4 (Development of B cells and T cells) Flashcards

1
Q

What is the phase 1 in B-cell precursors?

A

Repertoire Assembly; generation of diverse and clonally expressed B-cell receptors in the bone marrow (Lecture 1, Slide 2)

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2
Q

What is Phase 2 in B-cell precursor?

A

Negative selection; alteration, elimination or inactivation of B cell receptors that bind to components of the human body (Lecture 1; slide 2)

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3
Q

What is Phase 3 in B-receptor precursor?

A

Positive selection, promotion of fraction of immature B cells to become mature B-cells in the secondary lymphoid tissues

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4
Q

What is Phase 4 in B-cell precursor?

A

Searching for Infection

- recirculation of mature B cells between lymph., blood, and secondary lymphoid tissues

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5
Q

What is Phase 5 of B cell precursors?

A

Finding Infection; activation and clonal expansion of B cells by pathogen derived antigen in secondary lymphoid tissues

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6
Q

What is Phase 6 of B-cell precursor?

A

Attacking infection

- differentiation to antibody secreting plasma cells and memory B cells in secondary lymphoid tissue

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7
Q

What happens to B cells in bone marrow?

A

acquire functional antigen receptors immunoglobulin rearrangement

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8
Q

Where do B cells develop?

A

Bone marrow and migrate to secondary organs (eg. lymph node, spleen, peyers patches)

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9
Q

What is CD34?

A

a characteristic of bone marrow stem cell

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10
Q

What is CD10?

A

A characteristic of common lymphoid progenitor cells along with CD34

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11
Q

What is CD127?

A

A characteristic of B-cell precursor along with CD10 and CD34

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12
Q

What is CD19?

A

A characteristic of CD19 along with CD127, CD10, CD34

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13
Q

What is a Pro-B-cell?

A

first of B cell lineage
self renewal
immunoglobulin gene rearrangement begins

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14
Q

What always precedes the formation of the light chain?

A

heavy chain

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15
Q

What phase includes D and J joining?

A

Early pro-B cell

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16
Q

What phase includes the V segment joining DJ?

A

Late pro-B cell

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17
Q

What phase includes the expression of functional heavy chain?

A

Large pre-B cell

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18
Q

What phase includes the light chain rearrangement and assembled with heavy chain in ER proliferation?

A

Small pre-B cell

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19
Q

What phase includes membrane bound IgM-association with Ig alpha and Ig beta ( B cell receptor complex formed)

A

Immature B cell

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20
Q

What happens to nonproductive rearrangements?

A

do not get translated into functional protein

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21
Q

What happens to productive rearrangements?

A

They form complete and functional immunoglobulin

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22
Q

What is the benefit of having two chromosomes?

A

Allows two chances to make functional immunoglobulin

These productive rearrangments require Rag1 and Rag2

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23
Q

What is the default pathway for pro-B cells?

A

To die via apoptosis unless survival signal received

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24
Q

Where does early pro-B cell H chain gene rearrange?

A

D-J rearangements on both chromosomes

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25
Q

Where does late pro-B cell heavy chain gene arrangement occur?

A

V-DJ rearrangement on first chromosome (productive rearrangement)

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26
Q

Where does nonproductive rearrangement occur?

A

in,

  • V-DJ rearrangement on second chromosome
  • signaled to die by apoptosis
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27
Q

Where does productive rearrangement occur?

A

signaled to survive and become pre-B cells: 50% of cells

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28
Q

What are the two criteria of pro-B cell to survive?

A
  • able to make a heavy chain

- heavy chain must be able to bind to light chain

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29
Q

What are surrogate light chains?

A

VpreB and lambda5

  • binds in ER (pre B cell receptor)
  • mediate binding to receptors on stromal cells
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30
Q

How are functional pre-B cell receptors formed?

A

signal sent through IgB-shuts down gene arrangement and induces proliferation of pro-B cell

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31
Q

What is allelic exclusion?

A

-cell only expresses one of its two copies of a gene
gives homogenous B-cell receptors with
high avidity binding

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32
Q

What are consequences of no allelic exclusion?

A

low avidity binding-heterogeneous pentameric IgM

-overall decrease in specificity (pg 957 Section 6-4)

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33
Q

Describe pre-B cell receptor assembly?

A

Signals through the IgB subunit shuts down RAG gene transcription, RAG proteins degraded, and chromatin structural changes to prevent rearrangement

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34
Q

We do not want B cells with more than one functional ___________ chain?

A

heavy

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35
Q

What is another term for nonproductive rearrangment?

A

not spliced

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36
Q

Are successful rearrangements possible at the immunoglobulin light chain loci?

A

Yes

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37
Q

What are the steps for pre-light chain development?

A
  1. ) Must HAVE FUNCTIONAL HEAVY CHAIN
  2. ) AFTER LARGE PRE-B- CELL PROLIFERATES-(have many small pre-B cells)
  3. ) light chain rearrangement now occurs
  4. )RAG GENES ACTIVATED
  5. ) ONLY 1 RECOMBINATION EVENT NECESSARY-CAN HAVE SUCCESSIVE REARRANGEMENT EVENTS
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38
Q

WHAT ARE THE RESULTS OF LARGE B-CELL EXPANSION?

A
  1. ) INVESTMENT TO MAKE HEAVY CHAIN IS NOT LOST (85% MAKE FUNCTIONAL LIGHT CHAIN)
  2. ) DIVERSE POPULATION - SAME HEAVY CHAIN, BUT DIFFERENT KAPPA AND BETA CHAINS (DIFFERENT ANTIGENIC SPECIFICITIES
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39
Q

HOW MANY LIGHT CHAIN LOCI ARE PRESENT IN THE PRE-B CELL?

A

4 LIGHT CHAIN LOCI

 1. ) REARRANGE KAPPA GENE ON FIRST CHROMOSOME 
 2. ) REARRANGE KAPPA GENE ON SECOND CHROMOSOME
 3. ) REARRANGE LAMBDA GENE ON FIRST CHROMOSOME
 4. ) REARRANGE LAMBDA GENE ON SECOND CHROMOSOME

-MULTIPLE ATTEMPTS LFOR REARRANGEMENT

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40
Q

WHERE ARE CHECKPOINTS FOUND IN BONE MARROW TO ENSURE QUALITY OF IMMUNOGLOBULIN CHAIN?

A
  1. ) AFTER HEAVY CHAIN GENE REARRANGEMENT (selects for functional heavy chains)
  2. ) AFTER LIGHT CHAIN GENE REARRANGEMENT (select for functional light chains)
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41
Q

What happens to an pro-B cell if no pre-B cell receptors form?

A

apoptosis

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42
Q

What happens to the pre-B cell if it can not bind to the B cell receptor?

A

apoptosis

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43
Q

What stage of immunoglobulin chain production does the B cell commit to B-cell lineage?

A

early pro-B cell

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44
Q

What stage of immunoglobulin chain production generates heavy chain gene diversity in the pro-B cell population?

A

Heavy-chain gene arrangement

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45
Q

What stage of immunoglobulin chain production generates light-chain gene diversity in the pre-B cell population

A

Light chain gene rearrangement

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46
Q

What stage of immunoglobulin chain production makes functional IgM?

A

Immature B cell

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47
Q

What are Kit, IL-7 receptor, and CD25 have in common?

A

They are all growth factor receptors found in the Early pro-B cell, late pro-B cell, and large pre-B cell respectively

48
Q

Where is RAg 1 and 2 most common in?

A

Late Pro B cell and immature B cells

49
Q

Where are surrogate light chain components most commonly found?

A

Early pro-B, Late pro-B, large pre-B, and small pre-B

50
Q

What are the names of the B-cell populations?

A

B-1 and B-2

51
Q

What is the function of B-1 cells?

A

express CD5 (a marker for T cells)-~5% of B-cells-less diverse, low-affinity antibodies that bind many different antigens (polyspecific)-recognize bacteria polysaccharides, not protein recognition

(Lecture 1, slide 16)

52
Q

What are the characteristics of B-2 cells?

A
  • first produced after birth
  • extensive VDJ junctions
  • Diverse V region repertoire
  • primary location: secondary lymphoid organs
  • replaced from bone marrow
  • low spontaneous production of immunoglobulin
  • Secrete more IgG than IgM
  • required for T cell help
  • somatic hypermutation occurs
  • memory development: yes
53
Q

What are the primary sites for B cells?

A

-blood, lymph, secondary lymphoid organs, bone marrow

54
Q

What is the selection process for B-cell?

A

Self reactive immature B-cells bind self-antigen-up to 75% of immature B cells can recognize self antigen

55
Q

What is the negative selection process?

A

starting in bone marrow

- only those that don’t recognize self-antigens leave the bone marrow

56
Q

What is receptor editing?

A

retained and given a chance to rearrange receptor

57
Q

What is clonal deletion?

A

Successive new receptors are self-reactive. No further rearrangements are possible and the immature B cell undergoes apoptosis

58
Q

What are monovalent self-antigens?

A

antigens that carry one epitope

59
Q

What is anergy?

A

Self-reactive B cells that bind monovalent antigens to become inactivated and unresponsive to the antigen(different than the multivalent antigen-binding B-cells)
DO not DIE but cannot bind to any antigen*

60
Q

What are anergic B cells?

A

Short life span (1-5 days vs 40 days)- make IgD and IgM, but IgM cannot assemble a functional B cell receptor

61
Q

What are the three fates of self-reactive B cells?

A
  1. ) receptor editing- loss of reactivity (can happen when recognize more than 1 self antigen)
  2. ) apoptosis
  3. ) anergy (w/ monovalent antigen)
62
Q

What is central tolerance?

A

tolerance to self-antigens that are generated in B cell and T cell populations during their development in the primary lymphoid tissues

63
Q

In the periphery, how would you describe the antibody receptors?

A

receptor editing is no longer an option upon encountering self antigen now-die by apoptosis or become anergic

64
Q

What is peripheral tolerance?

A

tolerance to antigens outside the bone marrow

65
Q

Where do B cells circulate?

A

blood, secondary lymphoid organs, and lymph

66
Q

What is CCL21?

A

chemokine expressed in lymph node cortex and dendritic cells in lymph nodes
- attracts immature B cells to HEV

67
Q

What is CCR7?

A

expressed on B-cell

68
Q

What is CCL19?

A

chemokine expressed by dendritic cells in lymph nodes

69
Q

Where do B-cells congregate?

A

primary lymphoid follicle

70
Q

What is CXCL13?

A

chemokine that attracts B cells into the primary follicle

71
Q

What drives the maturation of immature B cells?

A

interactions with follicular dendritic cells and cytokines

72
Q

What are follicular dendritic cells (FDCs)?

A

specialized stromal cells-NOT of hematopoietic origin-secrete CXCL13 (not dendritic cells)

73
Q

What type of B cells do not encounter antigen?

A

naive B cells

74
Q

How do B cells try to survive?

A

they compete for access to follicular sites to survive

75
Q

What are thymocytes?

A

immature T-cells

76
Q

What is the Thymic stroma?

A

network of epithelial cells

77
Q

When is the thymus fully developed? And when does it degrade?

A

at birth, and degrade by year post-birth

78
Q

What is thymic involution?

A

fat gradually take over area-reduced production of T cells with age

79
Q

Is the Thymus required for T-cell immunity once estabished?

A

not required

80
Q

What is the correlation between age and fat?

A

fat takes up thymus tissue as age increases

81
Q

What is the fate of uncommon progenitor?

A

induced to divide and differentiate upon contact with stroma

82
Q

What is the double negative mean?

A

lack CD4 and CD8

83
Q

What is flow cytometry?

A

uses laser light source to excite particles to be detected by scatter detector

84
Q

What is a single cell suspension graph?

A

Shows distribution of CD8 and CD4 cells in thymus.
- not a lot of only CD4 and only CD8 cause they are leaving the thymus

  • higher number of both because they are originated in the thymus
85
Q

What receptors are found in uncommitted progenitor cells?

A

CD34 and CD44

86
Q

What receptors are found in the double negative thymocyte committed to the double negative thymocyte committed to the T cell lineage

A 
CD2
CD5
CD127
CD1A
Rag Complex
87
Q

What is the function of CD2?

A

Adhesion and signaling

88
Q

What is the function of CD5? `

A

adhesioon and signalijng

89
Q

What is the function of CD127?

A

cytokine receptor

90
Q

What is the function of CD127?

A

Cytokine receptor

91
Q

What is the function of CD1A?

A

MHC class I-like molecule

92
Q

Wha is the function of CD4 and CD8 (general terms)?

A

co-receptors

93
Q

What does RAG complex function as?

A

recombinase

94
Q

What signal is required for T-cell development and why?

A

Notch signaling because it is a quick response b/c of intracellular domain is transcription factor
- this drives proliferation of cells

95
Q

What are the two lineages of T-cells?

A

alpha:Beta and gamma:beta expression of TCR determines

“Race” for rearrangments

Results in gamma: delta or pre-T cell receptor

96
Q

What determines the committed alpha:beta and gamma:delta?

A

“Race” for rearrangment

97
Q

How can a committed alpha:beta T cell be formed?

A

If the beta rearrangement occurs forming an uncomiited double-positive thymocyte
then, alpha wins the rearrangment and forms alpha:beta T cell

98
Q

How are committed gamma:delta T cells formed?

A

when a beta arrangment “wins” forming uncommitted double-positive thymocyte B-chain
then, delta wins reaarangment and forms it

99
Q

What rearrangement occurs more often?

A

Beta chain to form uncommitted double positive thymocyte

100
Q

What is pTalpha?

A
  • surogate alpha chain-binding occurs in ER
  • serves as its own ligand-testing for proper conformation-induces Lck activation-signals to stop rearrangment beta,gamma, and delta
  • calls are now pre T cells
101
Q

What receptor (exclusively spoken about in class) does not occur in single positive ?

A

Notch 1 receptor

102
Q

What is the differences between medullary cells and dendritic cells?

A

Medullary epithelial cells are of thymic origin

Dendritic cells are of bone marrow origin

103
Q

What is a double positive thymocyte?

A

Contains CD4 and CD8 receptors

104
Q

Where does positive and negative selection occur?

A

alpha:beta doiuble positive T cells

105
Q

What is an example of positive selection?

A

only 2% of T cells will survive selection-receptors can interact with MHC I or II receptors made by that individual (Lecture 1, slide 38)

106
Q

Where does the T cell selection process occur?

A

Cortex

107
Q

Where does cell proliferation originate in?

A

medulla

108
Q

What cells mediate positive selection in the thymic cortex and how are they able to do that?

A

Cortical epithelial cells,

present self peptides via MHC I and II molecules (CD4:MHC II, CD8: MHC I)

109
Q

How long do alpha:beta cells have to bind to an epithelial cell before they have to perform apoptosis?

A

Binding within 3-4 days

110
Q

How does binding of alpha:beta T cell affect Reg gene?

A

it decreases RAG gene transcription and increase in the protein degradation

111
Q

T/F: Receptors rearrange the B-chain if it doesn’t bind over the 3-4

A

false: Receptors can rearrange alpha chain if it doesnt bind over the 3-4 days

112
Q

What is the cytotoxic receptor?

A

CD8

113
Q

What is the T-helper receptor?

A

CD4

114
Q

What is negative selection and what is it regulated by and what is it transcribed by?

A
  • **cells that bind too tightly may be autoreactive-and are eliminated
  • **regulated by numerous cell types-bone marrow- derived dendritic cells and macrophages
  • ** transcribed by the transcription factor autoimmune regulator (AIRE) (subpopulation of epithelial cells in medulla of thymus express tissue specific genes)
115
Q

What are Tregs?

A

***Cells that express CD25 on surface-when bind self-antigen: MHC complex, will suppress proliferation of naive CD4 T-cells binding the same antigen

116
Q

T/F: Mature T cells are long lived and circulate for many years?

A

True

Immunology (7 decks)

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