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TCR and T Lymphocyte development in thymus Flashcards

1
Q

What happens if we can’t make T cells?

A

Super susceptible to oppurtunisitc infections

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2
Q

Four markers on every T Cell?

A

TCR, CD2, 3, 28

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3
Q

Name the two types of antigen-specific TCR dimers

A

alphabeta (90-95%)

gammadelta

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4
Q

Gene difference between beta/gamma and alpha/delta.

A

beta and gamma have VDJC

alpha and delta have VJC ((NO D))

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5
Q

Three similarities between TCR and Ig?

A
  1. Bind Antigens
  2. Variable Region + Constant Region
  3. Heterodimer Binding Site
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6
Q

Purpose of the CD3 chain?

A

CD3 tranmits signals

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7
Q

Components of the CD3 molecules?

A

Gamma and Epsilon

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8
Q

T cells originate in the _____, migrate to the ______, then move to the _______

A

Bone Marrow
Thymus
Secondary Lymphoid

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9
Q

Thymus allows differentiation into…

A

CD4 (FoxP3 +/-)
CD8
NKT

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10
Q

What causes T cells to become functional memory or effector cells?

A

Maturation in LN following antigen recognition

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11
Q

List the two parts of the thymus

A

Cortex and Medulla

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12
Q

What cells of BM origin can be found in the thymus?

A

T cells and Dendritic Cells

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13
Q

Where are immature cells found in the thymus?

More mature cells?

A

Cortex

Medulla

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14
Q

Markers of immature thymocytes?

A

DN (CD4-CD8-)

DP (CD4+CD8+)

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15
Q

What percentage of thymocytes make it through education and selection?

A

2%

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16
Q

Markers of mature thymocytes?

A

CD4+CD8-

CD4-CD8+

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17
Q

Unique cell type found where mature T cells proliferate

A

Hassall’s corpuscle

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18
Q

Describe the size in the thymus over a lifetime.

A

Fully developed before birth
Grows until puberty
Shrinks in adult life

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19
Q

Who should and should not worry about thymectomy?

A

Adults losing thymus are probably fine, they’ve got enough T cells.
It can cause infant to be immunocompromised

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20
Q

Why does it matter a smidge if you perform a thymectomy on an adult?

A

Inhibition of vaccine efficiency in the elderly.

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21
Q

Markers present on an uncommitted progenitor cell.

A

CD34 - Stem Cell Surface Marker

CD44 - Adhesion

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22
Q

Markers present on a double negative thymocyte.

A

CD2,3 - Adhesion/Signalling
Il-7 – Cytokine receptor
CD1A - MHC class-I-like molecule

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23
Q

What provides the cue to initiate T cell differentiation in the thymus?

A

Notch receptor cleavage

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24
Q

Where does T cell gene rearrangement occur?

A

Thymus

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25
How does T cell DNA rearrangement go down?
Germline DNA recombination, transcription/splicing/translation of recombined proteins
26
Who has VDJC? alpha or beta?
beta
27
Who has VJC? alpha or beta?
alpha
28
Significance of D segment reading in three frames?
Can generate bonus diversity.
29
Which receptor type can generate more unique binding types?
T cells (10^18)
30
How does DJ combination in T cells occur?
1. RAG cleaves hairpins, adds P nucleotides 2. TdT adds "N" nucleotides 3. Incomplete hybridization 4. Gaps filled by mismatch/repair machinery.
31
Effects of expression of the beta chain?
beta chain rearrangement stops alpha transcription starts cell proliferation CD4/8 induction
32
Order in which the gene fragments rearrange in T cell dev.
DJ --> V-DJ --> beta produced | VJ --> alpha produced
33
Markers on a cell with a complete beta chain, but no alpha
CD25, CD44 low
34
How many changes does the beta chain get to rearrange correctly?
Two | Try with C1, then again with C2
35
Successful rearrangement of one beta copy will... | How does this compare to alpha?
block that at the other chromosome. Also blocks gamma and delta. Alpha leaves the other alone. T cells can have differing As
36
Which chain, alpha or beta, can undergo many functional rearrangement attempts?
Alpha
37
How does a cell decide whether or be alphabeta or gammadelta? (By that I mean....explain this process)
Initially, race between beta and gamma/delta to see who can rearrange fastest. It beta wins, it shuts down the other beta and whatever gamma/delta progress has occurred. Next, beta triggers the race btw alpha and gamma/delta. If alpha wins, you have an alpha/beta.
38
Which T cell type is most common, alphabeta or gammadelta.
alphabeta
39
Six different kinds of molecules in a TCR complex?
zeta, epsilon, gamma, delta, alpha, beta
40
What cells perform positive selection? Where is it?
Macrophages | Dendritic Cells
41
Alpha vs. beta. Most D Most J
D -- Beta (alpha has 0) | J -- alpha (61 comp. to beta 13)
42
What signaling happens when gammadelta chain rearrangement happens.
Signals through TCR receptor to stop further rearrangement.
43
Rearrangement of the alpha chain always eliminates..... | Why is this important
delta chain | Makes no gammadelta possible
44
Most gammadeltas do not express...
CD4 or CD8
45
What do gammadeltas do?
Anti-bacterial/viral/tumor functions
46
Gammadelta T cells recognize..
``` HMB-PP Host MHC1b (T10/22, MICA, MICB_ Nonprotein alkylamines Mycobacterial HSP Superantigens ```
47
Do gammadelta cells require antigen processing? presentation?
No. | No.
48
CD8 binds... | CD4 binds...
MHC1 | MHC2
49
What are CD4 cells there for?
Regulation of other immune cells
50
What cells do CD4s act on?
B Cells Macrophages Tissue Cells
51
What expressed T/10/22, MICA,MICB?
Transformed Cells
52
How many domains in a CD4 cells?
4
53
CD8 is a ______dimer
hetero
54
What does CD8 bind?
The alpha3 subunit of the MHC
55
What does CD4 bind?
The beta2 subunit of MHC
56
How do T cells decide whether to be CD4 or CD8?
When binding to thymic epithelial cells, those with a stronger affinity for MHCI are turns CD8. Those with stronger affinity for MHCII are turned CD4
57
What does positive selection assess? What cell markers does the T cell have at this point?
Ability to bind either peptides on MHC I or II. | Its double positive
58
What happens in negative selection?
Cells that bind self too strongly are killed.
59
How long do the double positive cells have to grab onto the thymic epithelial cells?
3-4 days
60
What cells carry out negative selection?
Dendritic cells and macrophages of the Corticomedullary Junction
61
What happens to cells that escape negative selection byt can still bind self.
Probs anergy.
62
Different purposes of DCs of the thymus and the periphery?
Thy -- Selection | Periph. -- Activation
63
Increasing # of MHC receptors increases Positively selected by ____ times and negatively selected by _____ times.
Pos -- N | Neg -- N^2
64
What is the N that results in the max T cell repertoire?
~13
65
Before bone marrow replacement, what must be done?
Irradiation and Chemotherapy
66
Why does it matter that donor and recipient MHCs match in a Bone Marrow Transplant.
When the new T cell are developing, they will be positively selected based on their ability to bind the host's MHC. The new APC MHC's will be fron the donor. If the host and donor MHCs don't match, none of the new T cells will be able to interact with the APCs.
67
Syndrome in which no thymus develops?
DiGeorge Syndrome
68
Why isn't it a big deal when folks over 60's thymus basically gives up?
T memory cells are still around
69
What happens to T cells after activation in 2LN?
Clonal Expansion
70
What does clonal expansion facilitate?
Regulated, Regional Immune Response
71
In what stage is TdT expressed?
All of them
72
In what stage is CD2 expresed?
From Pre-TCR on

Immunology (10 decks)

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