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HDM - Final > Immunogenetics - Bowden (Completed) > Flashcards

Immunogenetics - Bowden (Completed) Flashcards

1
Q

What part of the TCR complex is part of signal transduction? 7

A

The 2 ζ chains (3 ITAMs each)

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2
Q

What is unique about gene arrangement events in B cells? What do we call this? 11

A

Process called Clonal selection

Gene arrangement events occur in the ABSENCE of Ag

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3
Q

What is Allelic Exclusion? 11 (Add0

A

Monospecific, each arrangement codes for a particular receptr (add)

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4
Q

What is combinatorial Diversification? 13

A

Involves multiple germ line genes (one from mom, dad)

V-J or V-D-J recombination

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5
Q

What is Junctional Diversity? 13

A

Adding nucleotides during process of D-J or V to DJ joining

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6
Q

Light chain is to B cell as a __________ is to a T cell? 14

A

α chain

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7
Q

From left to right what is the order of VDJ on a gene? 15

A

V –> D –> J –> C

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8
Q

How many constant regions does a VDJ gene contain? What do they pertain to? 15

A

9 constant regions - one for each Ig region

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9
Q

What’s the order of joining of the V, D, J, and C regions of a germline gene? 18

A

D-J join –> V-DJ joining –> VDJ-C joining

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10
Q

What segment isn’t present in the light germline DNA of the BCR? 18

A

There is no D segment in the light chain

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11
Q

What process causes the excising of various V,D,J,C regions to end with a single segment of each? 19

A

Somatic Recombination

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12
Q

What is responsible for ensuring genes are joined in the correct order? 20

A

Recombination signal sequences (RSS)

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13
Q

What is the role of V(D)J Recombinase? 21

A

Forms the new regions between the various V,D, and J regions after they have been cut

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14
Q

What produces recombination activating genes (RAG-1 and RAG-2)? 21

A

Produced by lymphocytes

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15
Q

What is the role of terminal deoxyribonucleotidyl transferase (TdT)? 23

A

Adds nucleotides to asymmetrically cleaved hairpins - called P nucleotides

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16
Q

How do N nucleotides differ from P nucleotides? 23

A

P nucleotides - nucleotides added to asymmetric hairpins by TdT

N nucleotides - nucleotides added in a non-templated (random manner)

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17
Q

What does the addition of N and P nucleotides during junctional diversity do? 23

A

It further diversifies the third hypervariable region

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18
Q

What kind of errors are often seen during junctional diversity? What region does this occur in? 24

A

Frameshift mutations

Occur in the hypervariable region

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19
Q

For a single specific Ig how are the heavy and light chains manufactured? 27

A

The heavy and light chain are produced completely separate from one another for added variability

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20
Q

When does the second combinatorial diversity occur? 30

A

After both receptor chains have been expressed on the cell surface of the B or T cell

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21
Q

What is somatic hypermutation? 13

A

Point-mutations that occur in fully assembled chains (V-D-J and V-J)

Aka magic

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22
Q

Where would you find a T cell stem cell, pro-lymphocyte, pre-lymphocyte? 33

A

Within the generative organ of the bone marrow

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23
Q

In B cells which gets produced first, the heavy or the light chain? 36

A

Heavy then light

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24
Q

When does the CD19 marker become associated with a B cell? 37

A

At the Pro-B cell stage

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25
Q

What are the CD markers for B stem cells? 37

A

CD43+

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26
Q

What are the CD markers for Pro-B cells? 37

A

CD43+

CD19+

CD10+

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27
Q

What are the CD markers for Pre-B Cells? 37

A

CD43+ (B220lo)

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28
Q

When is the heavy chain added to a B cell? What else is present? 37

A

At the Pre-B stage, a surrogate light chain is also present

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29
Q

When is the light chain added to the B cell? 37

A

At the Immature B cell stage

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30
Q

What is the role of the surrogate light chain? 37

A

To hold the heavy chain in place as a place-marker until the light chain can be produced

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31
Q

Once it’s determined that the heavy chain of the Pre-B cell is functional what is the next step? 37

A

Proliferation of that cell

the heavy chain works so a bunch of copies are made to hopefully add a bunch of various light chains to gain diversity

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32
Q

When is the B cell checked for reactivity against self-Ags (negative selection)? 37

A

During the immature B cell stage after the light chain has been added to the BCR

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33
Q

What stops B cell heavy chain recombination? 38

A

Production of a successful, working Heavy chain

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34
Q

What does alternative splicing of mRNA have to do with Heavy chain expression? 40

A

Pre-mRNA can be processed in variety of ways

Initially pre-mRNA can be brought to and made contiguous with the μ or δ constant chain resulting in IgM or IgD

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35
Q

What is the role of Bone marrow stromal cells with B cells during their development? 41

A

Stromal cells express adhesion molecules and secrete cytokines to further development

36
Q

What stages of stromal cell support and B cell maturation involve VLA-4 and VCAM-1? 41

A

(Maturing B cell) VLA-4 — VCAM-1 (stromal cell)

  1. ) Stem cell/lymphoid progenitor
  2. ) Early pro-B cell
  3. ) Late pro-B cell
37
Q

What is the role of RAG 1 & 2? 21

A

Cleaves hair pin loops and ligases breaks back together

38
Q

What region defines the medulla of the Thymus? 44

A

The inner cortical region

39
Q

What region defines the thymic cortex? 44

A

The outer cortical region

40
Q

What T lymphocytes are present in the thymic cortex? 44

A

Double negative T cells (CD3-4-8-)

Double positive T cells (CD3+4+8+)

41
Q

What is the only route by which progenitor cells enter the thymus and mature lymphocytes leave the thymus? 45

A

Via the blood (No HEV)

42
Q

What stage of T lymphocyte leaves the bone marrow? 46

A

T lymphocyte stem cell heads to the Thymus before entering the pro-T stage

43
Q

When does the developing T cell achieve a CD marker of CD25+

A

At the pro-T stage within the cortex of the thymus

44
Q

At what stage is the first chain added to the T cell? What is the chain that is added first? 46

A

At the Pre-T cell stage the β-chain is added (α-chain surrogate)

45
Q

What markers are present on a T stem cell, Pro-T cell, and Pre-T cell? 46

A

T stem cell –> c-kit+, CD44+

Pro-T cell –> c-kit+, CD25+, CD44+

Pre-T cell –> c-kit+, CD25+

46
Q

During the maturation process how are CD4+ and/or CD8+ added to the developing T cell? 48

A

Developing T cells are first double-negative with no cluster differentiation

Next, the T cells are double-positive with both CD4+ and CD8+

Finally, either CD4+ or CD8+ is removed via proteolysis (what does this depend on?)

47
Q

What determines whether a developing T cell will be CD4+ or CD8+? 49

A

It’s based off what HLA class they interact with first

48
Q

Where is the TCR β gene locus found? 50

A

On chromosome 7

49
Q

What is a desired affinity for self-Ag for developing T and B cells? 52

A

Weak antigen recognition

50
Q

Differentiate positive vs negative selection. 52

A

Positive selection - Weak Ag recognition by a B or T cell = keep the cell

Negative Selection - strong Ag recognition by a B or T cell = degrade the cell

51
Q

What happens to a B cell that binds soluble self-Ags? 54

A

B cell is induced to become anergic

52
Q

What happens if a B cell, at first, binds self-Ag? 55

A

Occurs in anergic B cells that have been shut down due to self-Ag recognition

B cell undergoes receptor editing of the light chain

There are two genes λ κ

If κ is expressed and is self-reactive you can shut it down and try using the λ gene

If the λ gene works and is producing light chain that is not self-reactive tolerance is established and the new λ chain will eventually out-compete the κ chain

53
Q

How many genes are their for the light chain of a B cell?

A

2 –> κ and λ

54
Q

Why is IgM the first Ig produced by B cells? 56

A

It’s the first on the gene and therefore first expressed

55
Q

What’s happening during T cell positive selection? 58

A

Self-restriction establishment

Recognition of self-MHC

56
Q

What is the cluster differentiation of Tregs? 62

A

CD4

CD3

CD25 (receptor for IL-2)

57
Q

What is the function of Treg cells? 62

A

To inhibit self-reactive T cells

58
Q

What is the transcription factor that allows for Treg development? 62

A

FoxP3

59
Q

What is important to understand about clonal selection? 64

A

Happens within lymphocytes during development INDEPENDENT of Ag

60
Q

What do B cells undergo that T cells do not undergo? 65

A

Somatic Hypermutation

61
Q

What is a weak affinity required instead of no affinity for self-Ags for B and T cells?

A

Needed to stimulate the HLA response and so that they recognize what a self-cell

62
Q

Besides ensuring correct order of VDJ heavy segments, what does recombination signal sequences do? 20

A

Provides recognition sites for enzymes that cut and rejoin DNA

63
Q

What are the two light chain genes? 20

A

λ and κ

64
Q

What do errors in Junctional diversity often cause? 24

A

Frameshift mutations can triple the diversity of VDJ recombination (within the variable region)

65
Q

What is the second type of combinatorial diversity? 30

A

The rearrangement of:

Heavy & light chains - B cell

α/β or γ/δ - T cells

Completely randomized to allow for greater diversity

65
Q

Differentiate the markers for an immature B cell vs a mature B cell. 37

A

Immature B cell:
CD43-
IgM-lo

Mature B cell:
IgM-hi

66
Q

What stages of stromal cell support and B cell maturation involve Kit and SCF? 41

A

(Maturing B cell) Kit — SCF (stromal cell)

  1. ) Early pro-B cell
  2. ) Late pro-B cell
67
Q

What stages of stromal cell support and B cell maturation involve CAMs? 41

A

Stem cell/lymphoid progenitor cell

Pre-B cell stage

68
Q

What T lymphocytes are present in the thymic medulla? 44

A

Single positive:

Mature CD4+8- or CD8+4-

(Macrophages also)

69
Q

Where is the T cell α chain locus found? 50

A

On chromosome 14

70
Q

What is the total potential repertoire w/ junctional diversity? 50

A

10^(7) B and T cell clones

71
Q

What’s happening during T cell negative selection? 58

A

Central self tolerance establishment

Only T cells that don’t become activated by self-ag survive

72
Q

How many different possible Abs can be produced?

A

10^(14)

73
Q

Where are the two heavy chains for B cells encoded?

A

On chromosome 14

74
Q

What is the make-up of the light chain of a BCR?

A

either 2 κ or 2 λ make up the two light chains, but NEVER mixed

75
Q

What chromosome is the λ chain found on?

A

Chromosome 22

76
Q

What chromosome is the κ subunit found on?

A

Chromosome 2

77
Q

How many V, J, and C segments does the κ subunit of the light chain have?

A

3-35 V regions

5 J regions

1 C region

78
Q

What is the condition of a Pre T cell when it enters the thymus?

A

Double negative = no receptors

79
Q

What chromosome is the β chain of a TCR encoded from?

A

Chromosome 7

80
Q

Which cells is V(D)J recombinase expressed in?

A

Within immature B and T cells

81
Q

What does RAG 1 & 2 bind to?

A

RSS

12bp and 23bp spacers

82
Q

What is the mechanism of action for RAG 1 & 2 (walk-through)?

A

Both RAGs bind RSS (spacers) at the end of regions of interest (V,D,J regions)

The RAGs then come together forming a loop and cleave out an undesirable segment/region

Single loops can be combined with double loops, but never 2 single or 2 double

83
Q

What is somatic hypermutation?

A

Happens in B cells only after they have bound Ag and begins proliferation

During proliferation there are point mutations on the heavy and light chain resulting in affinity maturation

84
Q

What is the principle determinants for graft acceptance or rejection?

A

HLA proteins (Class I & II)

85
Q

Differentiate cleft binding for Class I vs Class II?

A

Class I: <10 aa

Class II: 13-25aa

86
Q

How many types of Class I HLA are there?

A

6 types

HDM - Final (15 decks)

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