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CMB2004 > L04 > Flashcards

L04 Flashcards

1
Q

what is expressed when the cells stay in the bone marrow

A

Pax5

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2
Q

what are the B cell-specific markers

A

CD45 then CD19

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3
Q

what is negative selection

A

removal of self reactive cells

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4
Q

what are the steps of making B cells

A

B cell precursor rearranges its immunoglobulin genes leading to generation of B cell receptors in the bone marrow

immature B cell bound to self cell-surface antigen is removed from repertoire (negative selection in the bone marrow

mature B cell bound to foreign Ag is activated leading to migration of B cells through the circulatory system to lymphoid organs and B-cell activation.

activated B cells give rise to plasma cells and memory cells (antibody secretion and memory cells in bone marrow and lymphoid tissue)

if B cells do not encounter Ag or see self Ag they die

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5
Q

what happens to pre-B cells before becoming immature B cells

A

H chain genes rearrange first (μ chain) moves to cell surface with Ig alpha and Ig beta and expressed with surrogate light chain (product of V preB and λ5 genes)

—> pre-B cell receptor (pBCR)

then light chains rearrange, and displace
V preB and λ5 chains (associating with H chain)

—>IgM BCR

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6
Q

when does D to Jh rearrangement happen

A

early pro-B cell

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7
Q

in what cells does heavy chain rearrangement stop and light chain gene rearrangement progress

A

Large pre-B cell

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8
Q

in what cells does light chain rearrangement stop

A

immature B cells

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9
Q

what does pre-BCR

A

Delivers signal to pre-B cell that H chain looks functional
no Ag required yet

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10
Q

what are the features of pre-BCR signal

A

Turns off RAG-1, RAG-2 genes

5 - 6 rounds of cell division

Surrogate light chain expression stops

RAG-1 and RAG-2 turned on again

L chain rearrangement starts

(RAG genes needed for gene rearrangement)

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11
Q

what is the most commonly expressed light chain in humans

A

kappa

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12
Q

what are the stages between stem cells and mature B cells

A

Stem cell

early pro-B cell

Late pro-B cells

large pre-B cell

small pre-B cell

immature B cell

mature B cell

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13
Q

when does Vh to DJh take place

A

late pro-B cell

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14
Q

when does V kappa to J kappa take place

A

from Large pre-B cell, small pre-B cell to immature B cell

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15
Q

when does V lambda to J lambda happen

A

Small pre-B cell to immature B cell

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16
Q

what happens when productive or nonproductive joining take place

A

check slide 9

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17
Q

what is the success rate of each rearrangement

A

1 in 3

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18
Q

what happens when pre-B cells that fail to generate non-productive re-arrangements of light chain kappa genes

A

they can be “rescued” by up to 10 further
rearrangements at the same locus, (as there are 5 Jk genes on each chromosome). If after all these attempts and still out of frame, then lambda locus will begin to rearrange

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19
Q

when are RAG 1 and 2 off

A

large pre-B cell

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20
Q

what is the function of RAG 1 and 2

A

lymphoid specific recombinase

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21
Q

what is the function of TdT

A

N-nucleotide

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22
Q

what is the function of lambda 5 and VpreB

A

surrogate light-chain components

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23
Q

what is the function of Ig alpha, Ig beta, SD45R, and Btk

A

signal transduction

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24
Q

what do immature B cells only express

A

IgM

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25
Q

what do immature B cells that bind multivalent self-antigen undergo

A

either

clonal deletion: cell dies by apoptosis
or

receptor editing: further light chain gene rearrangements of variable regions (get another chance)

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26
Q

what happens when immature B cells bind soluble self-antigen

A

cell becomes unresponsive

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27
Q

when is the heavy chain rearrangement done

A

Large pre-B cells

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28
Q

what is the surrogate light chain the product of

A

V preB and lambda 5 genes

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29
Q

how are the levels of μ and δ in anergic B cells

A

normal δ

low μ

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30
Q

Activated B cells in the periphery can develop into?

A

plasma cells, memory B cells

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31
Q

What is the fate of a pre-B cell with non productive re-arrangements of light chain genes?

A

They have up to 5 attempts on each kappa locus (= no. of J kappa genes) and then another four (no. of
J lambda genes) on each lambda locus

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32
Q

what are the 2 types of T cell genes

A

alpha and beta

delta and gamma

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33
Q

what are the types of alpha and beta T cells

A

CD4+ or CD8+

34
Q

what is the first round of selection and what does it eliminate

A

positive selection

eliminates alpha and beta T cells that do not bind to self MHC

35
Q

what is the second round of selection and what does it eliminate

A

negative selection

T cells that interact strongly with self antigen are eliminated

36
Q

what do the alpha and beta T cells in the thymus develop into

A

thymocytes

37
Q

what are the steps in developing thymocytes

A

1) re-arrange TCR genes (β first) and express TCR

-firstly, they rearrange TCRβ genes (similar to H chain in BCR)

-expressed along with pre-T cell receptor

-cells proliferate and then re-arrange TCR alpha genes

2) acquire other markers e.g. CD3, CD4, CD8

3) undergo positive and negative selection

38
Q

what are the features of the thymus

A

bi-lobed organ in anterior mediastinum

each lobe divided into many lobules

each lobule has outer cortex and inner medulla

39
Q

what cells are there in the thymus

A

lymphoid cells

epithelial cells

macrophages and dendritic cells

40
Q

whare does the first round of T cell selection happen in the thymus

A

the cortex

41
Q

whare does the second round of T cell selection happen in the thymus

A

the medulla

42
Q

T cells express TCR with CD3 and both CD4 and CD8 and then peripheral T cells express either CD4 or CD8

A

true

43
Q

what are the components of the CD3 complex

A

γ,δ,ε chains
ζ (zeta) chain dimer)

44
Q

what does the CD3 complex do

A

transmits signal to T cell nucleus following TCR recognition of p/MHC

45
Q

What is more diverse - gamma/delta TCR or alpha/beta TCR

A

alpha/beta

46
Q

Are alpha/beta and gamma/delta expressed on the same T-cell population?

A

No

47
Q

What percent of gamma-delta TCR is in circulation?

A

1-5%

48
Q

Where is gamma-delta TCR found?

A

epithelial tissues at mucosal surfaces

49
Q

Do alpha-beta and gamma-delta recognise the same antigents?

A

No

50
Q

Do gamma/delta TCR express CD4 or CD8?

A

No

51
Q

What is a ‘double-negative’ thymocyte?

A

CD3-4-8- (T cell not expressing any)

52
Q

What are the products of ‘double-negative’ thymocyte?

A

CD3+4-8- (export+selection in periphery) and large active ‘double-positive’ thymocytes (CD3+,pTalpha:beta+,CD4+, CD8+)

53
Q

What is the product of ‘double-positive’ large active thymocyte

A

Small resting ‘double-positive’ thymocytes

54
Q

What are the products of small resting ‘double-positive’ thymocytes?

A

small resting ‘single-positive’ thymocytes

55
Q

What are the three possibilities that T cells expressing randomly arranged alpha-beta TCRs may engage in?

A
  • recognise self MHC & “foreign” Ag = immunity
  • recognise self MHC & “self” Ag = autoimmunity
  • unable to recognise self-MHC
56
Q

What are the criteria for positive selection?

A

recognise self MHC & self peptide

57
Q

What cells undergo positive selection?

A

double-positive T cells

58
Q

Where does positive selection occur?

A

cortical epithelial cells in thymus

59
Q

What happens if cells are not recognised?

A

Apoptosis

60
Q

What percent of T-cells are capable of recognising own MHC?

A

1-2%

61
Q

Where do the positively selected cells move?

A

Medulla

62
Q

Where does the negative selection of T cells occur?

A

thymic dendritic cells/Mq with high affinity

63
Q

What causes to T cell apoptosis?

A

TCR binding to MHC/self-peptide with high affinity

64
Q

Why do T cells undergo apoptosis if they have high affinity?

A

Could induce autoimmunity

65
Q

What is the ultimate goal of TCR affinity for selection?

A

a population of T cells with low affinity for self peptide + self MHC

66
Q

What percent of T cells that survive thymic selection?

A

less than 5%

67
Q

What are the properties of T cells that survive thymic selection?

A
  • express TCR capable of binding self MHC
  • depleted of self-reactive cells
68
Q

What do CD8+T cells recognise?

A

Ag in association with MHC class I

69
Q

What do CD4+T cells recognise?

A

Ag in association with MHC class II

70
Q

What are the origin of thymocytes

A

HPC - bone marrow

71
Q

Process of elimination of self-reactive T cells?

A

Negative

72
Q

Site of T cell development and body location?

A

Thymus

73
Q

Gene segments for alpha and beta chains that get re-arranged?

A

VJ, VDJ

74
Q

Cells other than thymocytes present in the thymus are?

A

epithelial cells, APC

75
Q

Alpha or beta genes rearranged first?

A

Beta

76
Q

What is the pre-TCR?

A

a protein bound to rearranged TCRb that checks the assembly of b chain

77
Q

What does the CD3 molecule do and why is it important?

A

Multi-component signalling part of TCR; leads to T cell activation following peptide/MHC antigen binding

78
Q

Do gamma delta T cells normally express CD4/CD8?

A

No

79
Q

What is positive and negative selection of T cells?

A

TCR must recognize self MHC alleles in thymic cortex = +ve selection, then if a T cells TCR binds
self MHC and peptide too strongly in thymic medulla will die (-ve selection)

80
Q

If a T cell recognises peptide and MHC I which marker does it have on the surface?

A

CD8

81
Q

Are the criteria for positive and negative selection of immature T cells the same?

A

They are similar. They both involve
ability to recognise self MHC molecules, but the affinity of TCR for peptide/MHC forms the basis of the
differences

CMB2004 (12 decks)

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