Lecture 10+11: T Cells Flashcards

1
Q

Where do all lymphocytes development from

A

Hematopoietic stem cells

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2
Q

What is responsible from getting lymphocytes from HSC to lymphocytes

A

Stromal cells and cytokines

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3
Q

Where does T cell development occur

A

Thymus

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4
Q

Where do T cell progenitors originate

A

Bone marrow

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5
Q

What dictates movement of lymphoid progenitors to thymus

A

Chemokines

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6
Q

What cytokine is critical to development and commitment to T cell line

A

IL-7

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7
Q

What is IL-7 made by

A

Thymic stromal cells

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8
Q

Mutations in IL-7 lead to

A

No T cells

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9
Q

What do double negative thermocytes express to commit to T cell lineage

A

CD3 and CD5-adhesion and signaling molecules

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10
Q

Describe the role of Notch 1 and commitment to T cell lineage

A

Receptor for Notch 1 is on thymocytes, without notch 1 won’t transcribe for T cell lineage, once Notch 1 binds it cleaves repressors with proteases and activates T cell associated genes

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11
Q

What are the two T cell lineages

A

Gamma:delta
Alpha: beta

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12
Q

TCRs interact with linear peptides T or F

A

True

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13
Q

What do gamma:delta T cells express and where are they found

A

Express only CD3 and found in gut mucosa

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14
Q

What do Alpha:beta T cells express

A

CD4, CD8 and CD3

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15
Q

Which allele (gamma, delta or Beta) rearrangement increases likelihood to commit to T cell line

A

Beta allele rearrangement

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16
Q

What happens to T cells that do not make productive arrangements

A

Die by apoptosis

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17
Q

What percentage of T cells survive by making productive arrangement

A

2%

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18
Q

How many attempts do each B allele get to make successful rearrangement

A

2

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19
Q

How many total attempts for B chain rearrangements on chromosome

A

4

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20
Q

What genes are responsible for recombination

A

RAG1 and RAG2

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21
Q

Describe the steps in forming the Pre-T cell receptor

A

Ptalpha (invariant chain) checks the functionality of the Beta chain

If functional heterodimers form superdimer

Superdimer checks for interaction with CD3

Initiates rearrangement of alpha chain

Synthesizes CD8 and CD4

Proliferation of pre-T cell line

First T cell checkpoint

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22
Q

What genes are responsible for rearrangement of alpha chain in pre-t cells

A

RAG 1 and RAG2

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23
Q

What happens if rearrangement makes a functional alpha chain

A

Alpha chain is translocated into ER to check for interaction with B chain

Line proliferates

2nd T cell checkpoint

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24
Q

Combinatorial diversity

A

Separate rearrangement events for alpha and beta TCR chains so get diversity from that and how they interact, dictates antigen binding

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25
Q

Omenn syndrome

A

RAG deficiency lack T cells and B cells, opportunistic infections, must treat with bone marrow transplant or fatal

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26
Q

What is the first checkpoint in T cell development

A

After B genes rearrange

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27
Q

What is 2nd checkpoint for T cell development

A

After alpha genes rearrange

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28
Q

What is positive selection

A

Checks for TCR binding to MHC complexes

Weak or no binding- die

Strong moderate binding- live

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29
Q

Where does positive selection occur

A

Cortex of thymus

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30
Q

What determines CD4 and CD8 expression

A

Positive selection, receptor will either bind MHC I or MHCII

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31
Q

What is negative selection

A

TCR must recognize MHC complex but not bind too well, if it binds tightly to APC in thymus it undergoes apoptosis

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32
Q

At what point can a T cell migrate to secondary lymphoid organs

A

After undergoing negative selection and not tightly binding to MHC

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33
Q

What is CD28

A

Co-stimulatory molecule

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34
Q

What is CTLA-4

A

Inhibitory signal

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35
Q

What are the adhesions molecules in T cells

A

Integrins-LFA-1, VLA-4

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36
Q

Generation of mature T cells occurs in stages that are defined by ____

A

Certain proteins expressed on cell surface

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37
Q

What occurs in progenitor (pro-T cell) stage

A

Proliferation and initiation of somatic recombination of Beta chain

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38
Q

What occurs in precursor (pre-T cell) stage

A

Expression of B chain with surrogate alpha (pTalpha) and CD3 and zeta chains=Pre-TCR complex

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39
Q

What makes up the Pre-TCR complex

A

CD3 and zeta chains, PTalpha, Beta chain

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40
Q

What happens in double positive T cell stage

A

Alpha and beta chains successful rearranged and expressed along with CD3 and zeta chains as membrane bound BCR complex

Express CD4 and CD8

Positive and negative selection occurs

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41
Q

What happens in single positive T cell

A

Downregulation of either CD8 or CD4 and final maturation occurs

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42
Q

What happens a mature, naive T cell right after development ends

A

Released into circulation as single positive T cell

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43
Q

What happens when naive T cells encounter their antigen

A

Induce T cells to proliferate and differentiate, effector T cells perform function

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44
Q

How is delivery of antigen to lymphoid tissues aided by innate immunity

A

Dendritic cells deliver to lymphatic vessel, inflammation increases blood flow to infected sites as well as lymph

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45
Q

How do T cells enter lymph nodes

A

HEV or lymphatics from upstream lymph node

46
Q

How do T cells find their antigen

A

Naive T cells come from blood stream, migrate to peripheral lymph tissue and sample peptide: MHC complexes on dendritic cells

47
Q

What happens to naive T cells that don’t find their antigen

A

Exit issue and reenter blood- continual process of circulation

48
Q

What happens if T cells recognize antigen

A

Migration ceases, clonal proliferation and differentiation, give rise to memory and effector cells

Activated T cells reenter blood stream

49
Q

When can and can’t T cells exit lymph node

A

Once T cell is activated by antigen it must proliferate and can’t exit at that time, once proliferated those activated/effector T cells can exit

50
Q

Antigens in blood are carried by ___ to ___

A

APC’s to spleen`

51
Q

Pathogens in other sites are transported in ___ to ____

A

Lymph to regional lymph node

52
Q

Pathogens on musical surfaces are carried across mucosa and into ___ or ____

A

Tonsils or Peyers patches

53
Q

Describe the steps in how T cells enter lymph nodes/leave HEV

A

Circulating lymphocyte enters the HEV in lymph node

Binding L-selection, GlyCam-1 and CD34 allows rolling interaction

LFA-1 is activated by chemokines bound to ECM
Activated LFA-1 binds tightly to ICAM-1

Lymphocytes migrates into lymph node via diapedesis

54
Q

Is LFA-1 and L-selectin present on lymphocyte or HEV

A

Lymphocyte

55
Q

Is GlyCAM-1, ICAM-1 and CD34 on lymphocyte or HEV

A

HEV

56
Q

Where are dendritic cells located

A

Throughout body

57
Q

Where are macrophages located

A

Lymphoid tissue, connective tissue, body cavities

58
Q

Where are B cells located

A

Lymphoid tissue, peripheral blood

59
Q

What is the effect of activating dendritic cells

A

Results in activation of naive T cells

60
Q

What is the effect of activating macrophages

A

Activate macropahges

61
Q

What is the result of activating B cells

A

Delivery of help to B cells, antibody production

62
Q

During rolling interaction and binding if T cell finds antigen what happens

A

Induce conformational change in LFA to increase binding affinity

63
Q

What are the three signals for clonal expansion and differentiation in activating naive T cells

A

Signal 1- TCR:MHC binding (not enough)

signal 2-costimulatory signals promote survival and expansion of T cell clones (ex: B7 expressed on T cell binds CD28 on DC

Signal 3: cytokines direct T cell differentiation into different types of effector T cells

64
Q

Despite self testing on T cells in thymus some make it through, peripheral cells and non-activate dendrites do not express

A

Co-stimulatory molecules and Naive T cells don’t get activated

65
Q

Co-stimulatory signal alone, effect on T cell

A

No effect on T cell

66
Q

Antigen specific signal alone effect on T cell

A

Inactivation (anergy) or deletion of T cell

67
Q

If there is successful TCR:MHC binding what are the three survival transcription factors

A

NFAT, NFKB, AP1

68
Q

What cytokine is synthesized to promote survival and activation of naive t Cells

A

IL-2

69
Q

What does CD69 do

A

Retains stimulated T cell in lymph node for clonal differentiation and expansion

70
Q

What is S1P

A

Chemoattractant that is high in the blood and low in tissues.

71
Q

Do circulating naive T cells have high or low expression of S1P receptor

A

Low

72
Q

T cells not stimulated by antigen ____S1PR1

A

Reexpress which allows naive T cells to respond to S1P gradient and exit lymphatic tissue

73
Q

What happens when CD69 binds S1PR1

A

Cells internalized the complex and turn off S1PR expression, T cells in activation proliferate and differentiate and can’t leave

74
Q

What retains naive T cell in lymph node

A

CD69

75
Q

What causes proliferation of activated T cell

A

Express IL2 and IL2R via costimulatory signals with CD28

76
Q

What cytokine is critical for differentiation of T cells into effector and memory cells

A

IL-2

77
Q

Describe the steps in formation of IL-2R

A

Naive T cells express IL2 receptor gamma and betta, activation of these T cells leads to expression of alpha portion and induces proliferation

78
Q

What does cyclosporine do

A

Binds to cyclophilin within the cell and inhibits calceneurin preventing NFAT generation, without NFAT, transcription of IL-2 won’t occur which is necessary for T cell proliferation

79
Q

What is the ligand and receptor responsible for effector function of naive T cells

A

CD40 and CD40L

80
Q

Describe the relationship between CD40, CD40L and T cells

A

Activated T cells express CD40L which bind CD40

Leads to activation of macrophages-Th1 cell infected macrophage come together by binding CD40 and CD40L as well as MHCII and TCR and result in killing of intravesicular bacteria

Leads to activation of B cells to produce antibodies

81
Q

What is Hyper IgM syndrome

A

CD40/CD40L deficiency that doesn’t allow antibody class switching, no activation of macrophages

82
Q

what is CTLA-4

A

Inhibitory signal, binds B7 on APC to limit T cell proliferation, blocks CD28 signaling

83
Q

What are short lived cells for immediate immune response

A

Effector T cells

84
Q

what are long lived ells that respond to later infection with rapid, strong response, make new effector and memory cells

A

Memory cells

85
Q

What must be produced in order to continue survival of memory T cells

A

IL-7

86
Q

Describe steps of dendritic cell presenting to strong CD8+ T cell

A

Dendritic cell presents to naive T cell, dendritic cell sends sufficiently strong signal to activate CD8+ T cell effector status, activated T cell makes IL-2 to drive its own proliferation

87
Q

Describe steps when dendritic cell presents signal to weaker CD8+ T cell

A

Dendritic cell activates CD4+ T cell to help and secrete IL-2 and CD8+ T cells express IL-2 receptors, IL-2 from CD4+ drives clonal differentiation and proliferation of CD8+ T cell

88
Q

Once CD8+ Cells are activated how do they kill host cells

A

Apoptosis by releasing toxic granules

89
Q

What toxic granules do cytotoxic T cells have

A

Perforin-pore forming protein that allow granzymes to enter which are serine proteases that activate capsases in host cells to trigger apoptosis

90
Q

What cytokine produces Treg cells

A

TGF-B

91
Q

what cytokine produces TfH cells

A

IL-6

92
Q

What cytokines activate Th17

A

IL-6 and TGF-B

93
Q

What cytokines activate TH1

A

INF-y and IL-12

94
Q

What cytokine activate Th2

A

IL-4

95
Q

What is the role of TH1

A

Control bacteria that grow in macrophages, express INF-y and IL-2

96
Q

What is the role of Th2 cells

A

Control parasitic infection, express IL-4, IL-5, IL-13 that promote mast cells, eosinophils and B cell class switching to IgE

97
Q

What is the role of Th17 cells

A

Stimulate neutrophil response to extracellular bacteria and fungi

98
Q

What is the role of TfH cells

A

Stimulate antibody production from B cells including class switching and affinity maturation

99
Q

What does Treg do

A

Regulate immune response

100
Q

What bacteria can grow inside macrophage and phagosome, avoid detection by antibodies and CD8 T cells, inhibit fusion of phagosome and lysosome

A

Mycobacterium

101
Q

What stimulates macrophage and boots antimicrobial mechanisms

A

IFN-y and CD40 ligand

102
Q

What happens once macrophage is activated by TH1

A

Fusion of phagosome with lysosome and form reaction oxygen and nitrogen species

103
Q

Why not always have macrophages activated

A

Energy costly and reactive oxygen and nitrogen species can cause damage to host cells and tissues

104
Q

What drives Th2 cell differentiaiton

A

IL-4 in response to helminths and allergens

105
Q

What happens when activate Th2 in response to helminths

A

Mast cells secrete IL-4,

106
Q

What does IL-4 stimulate

A

B cell class switching to IgE

107
Q

What does IL-5 activate

A

Eosinophils

108
Q

What does IL-4 and IL-13 stimulate

A

Increased mucus secretion

109
Q

What drives Th17 differentiation

A

Pro inflammatory cytokines and TGF-B

110
Q

What does IL-17 do

A

Stimulates recruitment and production of neutrophils

111
Q

What does IL-22 do

A

Promotes epithelial integrity, antimicrobial peptides and mucin