T Lymohocytes Flashcards
(98 cards)
1
Q
What happens when immature T cells leave bone marrow?
A
migrate to thymus for development
2
Q
What is the goal of development?
A
mature T cells that leave thymus have diverse receptor specificity, are tolerant to self antigen, and recognize self MHC
3
Q
What are the 2 phases of T lymphocyte development?
A
- early phase
- second phase
4
Q
What happens in the early phase?
A
- commitment to T-cell lineage
- gene recombination
5
Q
What happens in the second phase?
A
- selection for cells with receptors that recognize self MHC
- selection against cells with receptors that recognize self antigen
- commitment to CD4 or CD8 lineage
6
Q
How do immature T cells know how to develop?
A
-move through different microenvironments which provide signals for the stages of development
7
Q
What do the signals for the stages of development come from?
A
binding receptors on cells and from cytokines
8
Q
Where do immature T cells enter the thymus?
A
at corticomedullary junction which is between the medulla and cortex
9
Q
How do immature T cells travel through thymus?
A
travel through cortex, finish development in medulla, before leaving thymus as mature T cells
10
Q
How long does T cell development take?
A
1-3 weeks
11
Q
T cell precursors that enter the thymus are…
A
double negative
12
Q
What does being double negative mean?
A
do not express CD4 or CD8
13
Q
What are the stages of the early phase?
A
- DN1 stage
- DN2 stage
- DN3 stage
- DN4 stage
14
Q
What is the DN1 stage characterized by?
A
cells that have CD44
15
Q
What happens during the DN1 stage?
A
- cells proliferate
- begin to express CD25
16
Q
What is the DN2 stage characterized by?
A
cells with CD25 and CD44
17
Q
What happens during the DN2 stage?
A
- recombination of TCR beta, gama, delta chains
- cells fully commit to T cell lineage
- lose expression of CD44
18
Q
What is the DN3 stage characterized by?
A
cells with CD25
19
Q
What happens in the DN3 stage?
A
- Beta selection
- lose expression of CD25
20
Q
What is beta selection in the DN3 stage?
A
- cells that have successfully undergone gene recombination of beta chain have become alpha beta T cells
- remaining cells become gamma delta T cells
- cells that are selected for express pre-alpha chain
21
Q
What is the DN4 stage characterized by?
A
cells with no CD44 or CD25
22
Q
What happens in the DN4 stage?
A
- alpha chain recombination of TCR
- cells gain expression of CD4 and CD8 (become double positives)
23
Q
What are the stages of the second phase of development?
A
- positive selection stage
- negative selection stage
- lineage commitment stage
24
Q
What happens in the positive selection stage?
A
- select for cells with TCRs that bind self MHC
25
What is it called when you select for cells that bind self MHC?
MHC restriciton
26
What happens in the negative selection stage?
select against cells that strongly bind to self-antigen
27
What does selecting against cells that strongly bind to self-antigen?
establishes self-tolerance
28
What happens during the lineage commitment stage?
silencing of either CD4 or CD8 gene to have either CD4+ or CD8+
29
What happens at end of second phase of T cell development?
mature T cells leave thymus and enter bloodstream
30
What do regulatory T cells (Tregs) express?
CD4, CD25, FoxP3
31
Where do regulatory T cells develop and what from?
in thymus from autoreactive T cell precursors
32
How do Tregs dampen immune response?
- compete for cytokines with other T cells
- secrete inhibitory cytokines
- inhibit professional APCs
- kill other immune cells
33
What is it called when Tregs compete for cytokines with other T cells?
cytokine deprivation
34
How do Tregs kill other immune cells?
using perforin and granzyme
35
Where does T cell activation occur?
lymph nodes/ secondary lymphoid tissues
36
What is required for T cell activation?
- TCR complex
- adhesion molecules
- co-stimulatory receptors
37
What does TCR bind to? (TCR complex)
MHC/antigen
38
What does CD4 or CD8 on TCR complex bind to?
-CD4 binds MHC-II
_ CD8 binds MHC-1
39
What does CD3 on TCR complex bind to?
doesn't bind to anything
40
What is the purpose of CD3 on TCR complex?
allows for transduction of signals in cell
41
What do adhesion molecules do?
adhere the cell to APCsW
42
What adhesion molecules do T cells express?
- LFA-1
- CD2
43
What does LFA-1 bind?
binds to ICAM-1 and ICAM-2 on APCs
44
What does CD2 bind?
binds to LFA-3 on APCs
45
What are co-stimulatory receptors required for?
to complete activation signaling
46
What are the co-stimulatory receptors?
- CD28
- CTLA-4
47
What does CD28 bind to? What does this do?
- binds to CD80 or CD86 on APCs
- activation
48
What does CTLA-4 bind to? What does this do?
- CD80 or CD86
- inhibition
49
What 3 signals does T cell activation require?
- TCR complex binds to MHC-antigen
- CD28 binds to CD80 or CD86
- IL-2 secreted by T cell, binds to IL-2 receptors on that same T-cell
50
What do the 3 signals that T cell activation requires stimulate?
proliferation of the T cell
51
What is proliferation?
- activated T cells divide 2-3 times a day or 4-5 days
- during this time, cytokines stimulate T-cells to differentiate into specialized effector cells and small subset of memory cells
52
What are polarizing cytokines?
cytokines secreted by immune cells due to PRR signaling
53
What do polarizing cytokines do?
act on proliferating T cells to cause differentiation
54
What does each subset of effector T helper cells have?
distinct cytokines (polarizing cytokines) that induce expression of a master gene regulator
55
What does the master gene regulator do?
regulates gene expression for cytokines (aka effector cytokines)
56
When are effector cytokines produced?
when the TH cells are fully differentiated
57
What are the different types of T cell differentiation?
- TH 1
- TH 2
- TH 17
- TFH
- Induced TReg
58
What polarizing cytokines are present in TH 1 differentiation?
- IL-12
- IFN - gamma
- IL - 18
59
What does TH1 differentiation result in?
expression of master gene regulator T-Bet
60
What effector cytokine does TH1 cell secrete?
INF- gamma, TNF
61
What polarizing cytokine is present in TH2 differentiation?
IL-4
62
What does TH2 differentiation result in?
expression of master gene EATA3
63
What effector cytokines do TH2 cells secrete?
- IL-4
- IL-5
- I-13
64
What polarizing cytokines are present in TH17 differentiation?
- IL-6
- IL-23
- TGF - beta
65
What does TH17 differentiation result in?
expression of master gene regulator RORY
66
What effector cytokines do TH17 cells secrete?
- IL-17 A
- IL- 17 F
- IL - 22
67
What polarizing cytokines are present in TFH differentiation?
- IL-6
- IL - 21
68
What does TFH differentiation result in?
expression of master gene regulator BC-1-6
69
What effector cells do TFH cells secrete?
IL-4 and I-21
70
What polarizing cytokines are present in Induced TReg differentiation?
IL-2 and TGF- beta
71
What does induced Treg differentiation result in?
expression of master gene regulator FoxB3
72
What effector cytokines do Induced Tregs secrete?
IL-10, TGF-beta
73
What do cytotoxic T cells's cell mediated response?
CD8 T cell response
74
What does the generation of effector cells require?
- interaction with MHC-1 antigen complex on APC
- help TH1 CD4+ effector cells
75
What is APC liscensing?
TH1 cells interact with professional APCs to allow for cross presentation
76
What is cross presentation?
expressing MHCII and MHCI
77
What are the licensing steps?
- TCR complex on TH1 cells binds to MHC-II antigen on professional APC
- CD40L on TH1 cell binds to CD40 on professional APCs
- results in cross presentation of MHC-I and MHC-II
78
How does CD8+ T cell activation occur?
- TCR binds to MHC-I antigen on licensed professional APC (CD* binds to MHC-I)
- CD28 on T cell binds to CD80 or CD86 on licensed APC
- IL-2 secreted by T cell binds to IL 2 receptor on same T cell
- results in proliferation and differentiation into cytotoxic T cells
79
Can licensing and CD8 T cell activation occur at the same time?
yes
80
What are the types of effector cytotoxic T cells?
- Tc1
- Tc2
81
What does Tc1 secrete?
IFN-gamma
82
What does Tc1 do?
kill infected cells via perforin and granzyme as well as Fas-FasL signaling
83
What does Tc2 secrete?
IL-4 and IL-5
84
What does Tc2 do?
kill infected cells using only perforin granzyme
85
What is the Kiss of Death?
cytotoxic T cells bind to infected cells
86
How does the kiss of death occur?
- T cell receptor binds to MHC-1 antigen on infected cells
- adhesion molecules bind surrounding TCR
- contents of CTL (centrosomes and granules) polarize to site of interaction
- granules of CTL exocytose and contents are released into synpase between CTL and infected cell
87
What ways does CTL kill?
- granzyme/perforin
- FasL
88
How does CTL kill using perforin and granzyme?
- TCR engagement results in an increase in Ca^2+ in CTL
- this results in exocytosis of perforin and granzyme
- perforin embeds in infected cell membrane and polymerizes to form holes in membrane
- granzyme enters cell and initiates apoptosis
89
How does CTL kill using FasL?
- FasL on CTL binds to Fas on infected cell
- signaling through Fas initiates apoptosis of infected cell
90
What are the types of memory T cells?
- Stem cell memory T cell (Tscm)
- Central memory T cell (Tcm)
- effector memory T cell (Tem)
- resident memory T cells (Trm)
91
Where are stem cell memory T cells found?
in secondary lymphoid tissues
92
What do stem cell memory T cells have the potential for?
becoming other types of memory T cells
93
Where do central memory T cells reside and travel between?
secondary lymphoid tissue
94
What happens when central memory T cells are activated?
can quickly develop into any type of effector cell based on cytokines that are present
95
What do effector memory T cells travel between?
travel between tertiary and lymphoid tissues
96
What do effector memory T cells exhibit?
exhibit effector function because they have undergone differentiation
97
Where do resident memory T cells reside?
in tertiary lymphoid tissueW
98
When are resident memory T cells ready to respond?
upon secondary infection
