Lectures 22 & 23 B and T Cell Development Flashcards

1
Q

hematapoietic stem cells (HSC) divide and the progeny become ____ cells in the bone marrow

A

common lymphoid progenitor

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2
Q

in what stages of life does the transformation of hematapoietic stem cells to common lymphoid progenitor cells occur?

A

begins in fetal life and continues throughout life

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3
Q

common lymphoid progenitor cells that are destined to become B cells acquire ___ on their surface

A

B220 (CD45R)

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4
Q

once B cells have successfully rearranged their BCR (Ig_), where do the cells travel to?

A

IgM; travel to periphery where they mature in the spleen and then circulate as mature naive B cells between blood and lymph nodes

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5
Q

what recombination occurs in progenitor B cells?

A

DJH chain recombination and start of V-DJ-H recombination

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6
Q

what recombination occurs in pro-B cells?

A

V-DJ-H chain recombination

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7
Q

in what stage of B cell development is u H chain expressed as the pre-BCR?

A

precursor Pre-B cells

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8
Q

what type of recombination occurs in the precursor pre-B cells?

A

VJL chain recombination

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9
Q

in the pre-B stage, the cells undergo several rounds of ____

A

cell division

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10
Q

in what stage of B cell development are mIgM expressed?

A

immature B cells

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11
Q

in what stage of B cell development does negative selection start?

A

immature B cells

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12
Q

what type of negative selection are immature B cells capable of?

A

deletion & receptor editing

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13
Q

in B cell development, what is the effect of positive IL-7 signals on 1. survival & proliferation, 2. RAG 1/2 3. Vh-DJh rearrangement (HC allelic exclusion)?

A
  1. promotes survival & proliferation
  2. decrease RAG 1/2
  3. decrease VH-DJh rearrangement
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14
Q

what is the effect of negative IL-7 signals on:

  1. pre-BCR & IL-7 signals
  2. RAG 1/2
  3. light chain VLJL rearrangement
  4. proliferation
A
  1. decrease pre-BCR and IL-7 signals
  2. increase RAG 1/2
  3. increase light chain VLJL rearrangement
  4. decrease proliferation
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15
Q

pre-BCR made up of u heavy chain & surrogate light chains inhibits ___ rearrangement and induces ___ rearrangement

A

u; k

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16
Q

u & k in the pre-BCR inhibit rearrangement of ___allele and ___ rearrangement

A

K and lambda

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17
Q

in what part of the body does negative selection first occur?

A

bone marrow

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18
Q

t/f many B cells die in the bone marrow due to negative selection

A

t

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19
Q

what is central tolerance?

A

loss of B cells with self-reactive autoantibodies form the bone marrow

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20
Q

how does central tolerance of B cells occur?

A

clonal deletion of autoreactive B cells

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21
Q

what is clonal deletion?

A

induced apoptosis of IgM+ immature B cells with self-reactive BCR while still in the bone marrow

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22
Q

autoreactive B cells that are not caught by clonal deletion, can undergo ____ editing

A

light chain receptor editing

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23
Q

what segments get rearrange in light chain receptor editing?

A

the remaining V and J segments on the same chromosome

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24
Q

some autoreactive B cells that escape clonal deletion become ___ due to exposure to self-antigen or become unresponsive to antigen, these cells are called ___ and are short-lived

A

anergic; transitional T3

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25
Q

in light chain rearrangement, the first rearrangement btwn __ and __ regions is productive, but the combination of teh resultant light chain with Ab results in an ____ antibody

A

V3 and J3; autoimmune

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26
Q

in light chain receptor editing, the second rearrangement btwn __ and __ is productive and the combination with Ab heavy chain results in an _____ antibody

A

V2 and V4; nonautoimmune antibody

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27
Q

does the transition from immature to mature B cells occur outside the bone marrow?

A

yes

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28
Q

T1 B cells migrate to the ___ where a second round of ___ and further maturation occurs

A

spleen; negative selection

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29
Q

self reactive T1 cells are eliminated by ___

A

negative selection

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30
Q

the maturation of T1 B cells to T2 B cells is done by ____ selection

A

positive

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31
Q

T2 B cells mature to ___ cells, the largest pool of B cells

A

B-2

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32
Q

the transition of T2 B cells to B-2 cells is dependent on stimulation through ____

A

BAFF receptor

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33
Q

B-2 cells circulate for ~____ months

A

4.5

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34
Q

B-1, B-2, and marginal zone B cells all express __ and ___ immunoglobulins

A

IgD and IgM

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35
Q

during B cell development, the BCR signals through ____ and ___

A

Ig alpga and Ig beta

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36
Q

the BCR iga/igB have ____ motifs which can become phosphorylated

A

immunoreceptr tyrosine-based activation motifs (ITAM)

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37
Q

cross linking the BCR brings ___ into close proximity and they will phosphorylate the ITAMs

A

src family tyrosine kinases

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38
Q

phosphorylated ITAMS of BCR become docking sites for ____ and once it docks and becomes activated it causes multiple signalling events

A

syk kinase

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39
Q

what is the requirement for T-dependent B cells development?

A

contact with T cells through CD40 (using CD40L) to co-stimulate

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40
Q

are memory B cells made as a result of T-dependent or T-independent development?

A

T-depenent

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41
Q

cytokines modify the response of T-dependent or T-independent B cell development?

A

T-dependent

42
Q

what causes B cell activation in T-independent (TI-1) B cell development?

A

polyclonal activators like some bacteria

43
Q

what causes T independent (TI-2) B cell development?

A

highly repetitious molecules (like polymeric proteins, cell wall polysaccharides which cross link BCR with CD21

44
Q

what are 3 proliferation cytokines that cause activated B cells to proliferate?

A

IL-2, IL-4, IL-5

45
Q

what cytokines cause proliferating B cells to differentiate into specific types of B cells?

A

IL-2, IL-4, IL-5, IFN-y and TGF-B

46
Q

IFN-y causes proliferating B cells to differentiate into ____ cells

A

plasma

47
Q

which B cells secrete IgG2a or IgG3?

A

plasma cells

48
Q

TGF-B causes proliferating cells to differentiate into plasma cells that produce what Ig?

A

IgA or IgG2b

49
Q

IL-4 causes proliferating B cells to differentiate into plasma cells that secrete what type of Ig?

A

IgE or IgG1

50
Q

IL-2, IL-4, and IL-5 cause proliferating B cells to differentiate into plasma cells that secrete what Ig?

A

IgM

51
Q

T cell development occurs in what gland?

A

thymus

52
Q

the thymus has well-defined ___ and ___ regions

A

cortical and medullary regions

53
Q

t/f the thymus is richly innervated

A

t

54
Q

what is the effect of stress on cortical thymocytes?

A

rapid loss, thought to be at least pertly bc of the effect of steroids such as glucocorticoids

55
Q

what happens to the size of the thymus during pregnancy and old age?

A

gets smaller (involutes)

56
Q

in older people, the involution of the thymus is associated with decreased function of ___ cells

A

T

57
Q

hematopoietic stem cells are attracted to the thymus from the bone marrow by ____

A

chemokines

58
Q

development of T cells in the thymus is dependent on the ___ being secreted from thymic epithelial cells and it binding to the receptor ___ on the lymphocyte

A

notch ligand; notch

59
Q

while T cells are developing in the thymus, they are called ____

A

thymocytes

60
Q

the maturation process of T cells takes between __ and __ weeks

A

1 and 3

61
Q

a prothymocyte enters the thymic cortex where ___ and ___ are expressed

A

Thy-1 and TDT

62
Q

when pre-T cells are in the stage of rearranging their TCR genes, they are called ___ or ___ cells

A

CD3+CD4-CD8- or double negative T cells

63
Q

double negative T cells that successfully rearrange their gamma & delta chain gene segments develop into the ____T cells that are exported to the periphery in small numbers

A

CD3+CD4-CD8- gamma/delta T cells

64
Q

what is allelic exclusion in T cell development

A

successful rearrangement of a set of TCR genes supresses further rearrangement of TCR genes on the second chromosome

65
Q

what is odd about the alpha chain of the TCR?

A

alpha V region proximal regions recombine first (3-5 cycles of V-J rearrangements per cell)

66
Q

t/f the majority of double-negative cells will go on to rearrange beta and alpha chain gene segments

A

t

67
Q

t/f gamma delta T cells with TCR that are encoded by specific V-gamma-gene segments are exported from the thymus at defined periods of fetal and newborn development and then migrate to populate epithelial rich tissue in adults

A

t

68
Q

the delta gene segments of the TCR are nested between ___ gene segments

A

alpha

69
Q

once a T cell rearranges its alpha segments of the TCR, the ___ segments will be lost

A

delta

70
Q

double positive T cells can undergo selection for reactivity to self to ensure what 2 things?

A
  1. self-tolerance

2. MHC restriction

71
Q

positive and negative selection of T cells in the cortex of the cotex of the thymus involves a ___ interaction between immature thymocytes and cells in the cortex

A

physical

72
Q

if the thymocytes bind too strongly to self cortex cells, what happens to them?

A

die by clonal deletion (neagtive selection)

73
Q

if thymocytes do not interact at all with the cortex epithelial cells, what happens to them?

A

death by neglect

74
Q

only thymocytes with what level of affinity for self-MHC on cortical thymic epithelial cells survive

A

low/intermediate (positove selection)

75
Q

thymocytes that are positively selected, upregulate ___ and migrate to the medulla

A

CCR7

76
Q

when thymocytes are positively selected, they become ___ or ___ cells

A

CD4 or CD8 single positive cells

77
Q

what are the 3 proposed models of lineage commitment in T cells?

A
  1. instructive model
  2. stochastic model
  3. kinetic signalling model
78
Q

what is the instructive model of T cell lineage commitment?

A

assumes multiple interactions between the TCR, CD4 or CD8 co-receptors and MHC instruct T cells to differentiate

79
Q

what is the stochastic model of T cell lineage commitment?

A

suggests that one co-receptor is shut off randomly, independently of interactions with the TCR

80
Q

what is the kinetic signalling model of T cell lineage commitment?

A

all cells show reduced CD8, so stronger positive selecting TCR results in CD4 but an interrupted TCR signal with IL-7 leads to CD8

81
Q

in negative selection of thymocytes in the medulla, there is a physical interaction between ____cells and the thymocytes

A

dendritic cells and macrophages

82
Q

what happens to thymocytes in the medulla if they have high affinity TCR for self MHC/self-antigen?

A

die by apoptosis

83
Q

thymocytes that make it through the cortex and medulla are released into the peripheray as ____, which require further maturation to naive T cells which is thought to be from further ___ interactions

A

recent thymic emigrants; MHC

84
Q

small populations of double positive T cells can become other cell types such a:

A

NKT cells, T reg cells and intraepithelial lymphocytes (IEL)

85
Q

while strong interactions between TCR and CD4 or CD8 in the thymus leads to ____, this strong interaction in teh periphery lead to ____

A

cell death; proliferation

86
Q

stimulation of T cells through the TCR is done in collaboration with ___

A

CD3

87
Q

what is the function of CD45 in TCR signalling?

A

CD45 is a tyrosine kinase that removes an inhibitory phosphate, activating the src kinase Lck

88
Q

Lck is associate with ___ and ____

A

CD4 and Cd8

89
Q

what is the function of Lck in TCR signalling?

A

phosphorylates the ITAMs on CD3 to which ZAP-70 docks

90
Q

what is the function of ZAP-70 in TCR signalling?

A

becomes phosphorylated and activated by lck then catalyses other phosphorylations that lead to gene expression, differentiation and activation

91
Q

what are hematapoietic stem cells?

A

stem cells that can differentiate into any type of WBC in the blood or tissues

92
Q

what are 3 types of lymphocytes?

A

mostly b and T cells, but can also have innate lymphoid cells

93
Q

what is a CLP?

A

common lymphoid progenitor

94
Q

why are RAG1/2 downregulated once a B cell has successfully rearranged its mu heavy chain?

A

if there was too much RAG1/2, the second allele may try to rearrange and that would cause issues

95
Q

can B cells express more than 1 heavy chain?

A

no

96
Q

increased RAG 1 & 2 results in more ____ chain rearrangement

A

light

97
Q

will light chain receptor editing happen if there are no other J regions?

A

no

98
Q

the ____ regions of IgM and IgD are identical and the ____ regions are different from each other

A

light chain/ variable region; constant

99
Q

can class switch occur in TI-1 or TI-2?

A

no, so they will only secrete IgM

100
Q

the Thy-1 in T cells is thought to be equivalent to the ___ of B cells

A

B220

101
Q

when babies are in-utero, they have ___ Tcells and after birth they are replaced by ____ T cells

A

delta gamma; alpha beta