T cell Development Flashcards
1
Q
What are the steps in the life of a T cell?
A
- T cell progenitors develop in the bone marrow and migrate to the thymus
- Positive and negative selection in the thymus
- Mature T cells migrate to the peripheral lymphoid organs
- Active T cells migrate to sites of infection
2
Q
What are Thymocytes?
A
Developing T cells within the thymus
3
Q
Which type of T cells maintain Tissue Integrity?
A
gamma:delta T cells
4
Q
Which type of T cell does not express CD8 or CD4 co-receptors?
A
Gamma:delta T cells
5
Q
Which type of T cells interact with non-classical receptors?
A
gamma:delta T cells
6
Q
Which type of T cells are considered Helper T cells?
A
CD4
7
Q
What are the subtypes of a CD4 cell?
A
- Th1
- Th2
- Th17
- Tfh
- Treg
8
Q
Which type of T cells regulate adaptive and innate immune function?
A
CD4 T cells
9
Q
Which T cells are cytotoxic?
A
CD8 T cells
10
Q
Which T cells have a direct effector function?
A
CD8 cells
11
Q
What is the site of all T cell development?
A
Thymus
12
Q
Selection of T cells happens as thymocytes move from ______ to ______ in the thymus.
A
- Cortex
2. Medulla
13
Q
TCR development happens where?
A
Cortex of Thymus
14
Q
What happens to the T cell production of the thymus with age?
A
It is reduced
15
Q
T/F T cells have long half lives
A
True
16
Q
What is the half life of a CD4 T cell?
A
4.2 years
17
Q
What is the half life of a CD8 T cell?
A
6.5 years
18
Q
T/F with the reduction of T cell production, T-cell mediated immunity is also greatly diminished
A
False, T cell-mediated immunity is not grossly affected
*probably because of the long half life
19
Q
What is Notch1?
A
T cell transcription factor complex
20
Q
What is Pax-5?
A
B cell transcription factor
21
Q
T cell progenitors don’t commit until they reach what?
A
The thymus
22
Q
When is the first checkpoint in T cell development?
A
Pre-T cell
23
Q
When is the second checkpoint in T cell development?
A
Positive and Negative selection
24
Q
Thymic location influences ________
A
T cell development
25
What dictates T cell lineage?
Gene rearrangement
26
What genes rearrange first?
Beta, Gamma, and Delta
27
T/F Gamma or Delta rearrangement enhances Beta and Alpha
False, is suppresses Beta and Alpha
28
Which T cells leave the thymus with little selection?
Gamma:Delta T cells
29
Beta chain production drives _________
CD4 and CD8 expression
*Double Positive
30
What would initiate an alpha:beta lineage?
B chain formation
31
Between Alpha and Beta, which chain is rearranged first?
Beta
32
How many attempts can be made to achieve a productive rearrangement of the Beta chain?
4 attempts
- Two attempts per locus
- Two genes
33
What is the order of rearrangement on the Beta chain?
1st: Vb-Db-Jb -> Vb-DJb
2nd: Vb-DJb -> VDJb
34
T/F Beta chain locus is organized similar to immunoglobulin chains
False, it is organized differently
35
Alpha chain rearrangement occurs in _________
Pre-T cells
36
Alpha chain rearrangement follows what?
Proliferation and CD4/8 expression
37
Just before alpha chain rearrangement, what is still a possible fate for this cell?
May still develop into gamma:delta T cells
38
Once you have had Alpha chain rearrangement what is no longer possible?
gamma:delta T cells
39
What purpose does Positive selection serve?
Selects for a functional T cell receptor
40
What purpose does Negative Selection serve?
Ensures no self-antigen binding
41
Within T cell development, what are the stages in development for a mature double-positive cell?
1. Poliferation and differentiation to double-positive CD3+ thymocytes
2. Positive Selection
3. Negative selectdion
4. Entry to the circulation
42
What are the thymocyte location and characteristics at the time of proliferation and differentiation to double positive CD3+ thymocytes?
Double-negative CD3- thymocytes in the subcapsular zone
43
Describe thymocyte location and characteristics at the time of positive selection
Double-positive CD3+ thymocytes in the thymic cortex
44
Describe Thymocyte location and characteristics during negative selection
Double-positive CD3+ thymocytes throughout cortex and especially at the cortico-medullary junction
45
Describe thymocyte location and characteristics as they enter the circulation
Mature self-restricted, self-tolerant, single-positive CD4 or CD8 T cells leave the thymus in blood venules
46
Positive selection ensures _____ is bound
MHC
47
Positive Selection of alpha:beta T cells is done by _______ in the ________-
1. Corical epithelial cells
| 2. Thymus
48
How do epithelial cells conduct positive selection?
- Epithelial cells present MHC I/II self-peptide complexes
- If the TCR binds moderately or strong it lives
- If the TCR has weak or no binding, it dies
49
In positive selection, TCR must bind MHC within ________
3 to 4 days
50
What effect does binding of TCR to MHC have on the RAG 1/2 complex?
It turns it off
51
T/F in the 3 to 4 days that TCR has to bind MHC, alpha chain rearrangement can occur
True,
I think this would be to modify it to bind with more affinity to MHC
52
T/F Positive selection is the second checkpoint in T cell development
True
53
What determines CD4 vs CD8 expression?
Positive Selection
54
How Does Positive selection determine CD4 or CD8 expression?
Basically, the T cell is presented with MHC 1 and 2 and whichever one it interacts with the best determines whether it is CD8 or CD4 lineage
55
During Positive Selection what would a Double positive thymocyte become if it interacted with MHC1?
A CD8 T cell
56
During Positive selection, what would a double positive thymocyte become if it interacted with a MHC II?
A CD4 T cell
57
What is required in positive selection to determin CD4 vs. CD8 expression?
Co-signaling
58
T/F There are different models of selection for CD4 or CD8 expression
True
59
What cells perform negative selection of alpha:beta T cells?
- Dendritic cells
- Macrophages
- Other cells in the thymus
60
How is negative selection performed?
1. Dendritic cells and macrophages present self-peptides
2. Excessively binding induces apoptosis
3. Moderate binding allows the cell to live
61
T/F Central Tolerance is a result of Negative selection
True
62
What other type of tolerance may also occur other than central?
Peripheral
63
T/F Following Selection, Naive Mature T cells are done differentiating
False, They can still undergo differentiation
64
Naive T cells can enter a draining lymph node by two routes. What are they?
1. In the blood
| 2. In the afferent lymph coming from an upstream lymph node
65
In the life of a T cell, what happens as T cell progenitors develop in the bone marrow and migrate to the thymus?
T-cell precursor rearranges its T-cell receptor genes in the thymus
66
In the life of a T cell, what happens during positive and negative selection? (in a general sense)
Immature T cells that recognize self MHC receive signals for survival. Those that interact strongly with self-antigen are removed from the repertoire
67
In the life of a T cell, what happens as Mature T cells migrate to the peripheral lymphoid organs?
Mature T cells encounter foreign antigens in the peripheral lymphoid organs and are activated
68
In the life of a T cells what happens as Activated T cells migrate to the sites of infection?
Activated T cells Proliferate and eliminate infection
69
Beta chain rearrangement forms ___________
Pre-T cell Receptors
70
During the first Checkpoint of T cell development, the beta chain binds a ________
Surrogate alpha-chain analogue (pTa)
71
T/F a CD3 complex is assembled during the first checkpoint in T cell development
True
72
What happens if signaling occurs during the first checkpoint of T cell development?
- Signaling drives further development
- RAG function halts
- Proliferation
73
T/F Pre-T cell receptor formation and the first checkpoint involves the formation of a superdimer
True
