Lecture 10+11: T Cells Flashcards
(111 cards)
1
Q
Where do all lymphocytes development from
A
Hematopoietic stem cells
2
Q
What is responsible from getting lymphocytes from HSC to lymphocytes
A
Stromal cells and cytokines
3
Q
Where does T cell development occur
A
Thymus
4
Q
Where do T cell progenitors originate
A
Bone marrow
5
Q
What dictates movement of lymphoid progenitors to thymus
A
Chemokines
6
Q
What cytokine is critical to development and commitment to T cell line
A
IL-7
7
Q
What is IL-7 made by
A
Thymic stromal cells
8
Q
Mutations in IL-7 lead to
A
No T cells
9
Q
What do double negative thermocytes express to commit to T cell lineage
A
CD3 and CD5-adhesion and signaling molecules
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
11
Q
What are the two T cell lineages
A
Gamma:delta
Alpha: beta
12
Q
TCRs interact with linear peptides T or F
A
True
13
Q
What do gamma:delta T cells express and where are they found
A
Express only CD3 and found in gut mucosa
14
Q
What do Alpha:beta T cells express
A
CD4, CD8 and CD3
15
Q
Which allele (gamma, delta or Beta) rearrangement increases likelihood to commit to T cell line
A
Beta allele rearrangement
16
Q
What happens to T cells that do not make productive arrangements
A
Die by apoptosis
17
Q
What percentage of T cells survive by making productive arrangement
A
2%
18
Q
How many attempts do each B allele get to make successful rearrangement
A
2
19
Q
How many total attempts for B chain rearrangements on chromosome
A
4
20
Q
What genes are responsible for recombination
A
RAG1 and RAG2
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
22
Q
What genes are responsible for rearrangement of alpha chain in pre-t cells
A
RAG 1 and RAG2
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
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
25
Omenn syndrome
RAG deficiency lack T cells and B cells, opportunistic infections, must treat with bone marrow transplant or fatal
26
What is the first checkpoint in T cell development
After B genes rearrange
27
What is 2nd checkpoint for T cell development
After alpha genes rearrange
28
What is positive selection
Checks for TCR binding to MHC complexes
Weak or no binding- die
Strong moderate binding- live
29
Where does positive selection occur
Cortex of thymus
30
What determines CD4 and CD8 expression
Positive selection, receptor will either bind MHC I or MHCII
31
What is negative selection
TCR must recognize MHC complex but not bind too well, if it binds tightly to APC in thymus it undergoes apoptosis
32
At what point can a T cell migrate to secondary lymphoid organs
After undergoing negative selection and not tightly binding to MHC
33
What is CD28
Co-stimulatory molecule
34
What is CTLA-4
Inhibitory signal
35
What are the adhesions molecules in T cells
Integrins-LFA-1, VLA-4
36
Generation of mature T cells occurs in stages that are defined by ____
Certain proteins expressed on cell surface
37
What occurs in progenitor (pro-T cell) stage
Proliferation and initiation of somatic recombination of Beta chain
38
What occurs in precursor (pre-T cell) stage
Expression of B chain with surrogate alpha (pTalpha) and CD3 and zeta chains=Pre-TCR complex
39
What makes up the Pre-TCR complex
CD3 and zeta chains, PTalpha, Beta chain
40
What happens in double positive T cell stage
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
41
What happens in single positive T cell
Downregulation of either CD8 or CD4 and final maturation occurs
42
What happens a mature, naive T cell right after development ends
Released into circulation as single positive T cell
43
What happens when naive T cells encounter their antigen
Induce T cells to proliferate and differentiate, effector T cells perform function
44
How is delivery of antigen to lymphoid tissues aided by innate immunity
Dendritic cells deliver to lymphatic vessel, inflammation increases blood flow to infected sites as well as lymph
45
How do T cells enter lymph nodes
HEV or lymphatics from upstream lymph node
46
How do T cells find their antigen
Naive T cells come from blood stream, migrate to peripheral lymph tissue and sample peptide: MHC complexes on dendritic cells
47
What happens to naive T cells that don’t find their antigen
Exit issue and reenter blood- continual process of circulation
48
What happens if T cells recognize antigen
Migration ceases, clonal proliferation and differentiation, give rise to memory and effector cells
Activated T cells reenter blood stream
49
When can and can’t T cells exit lymph node
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
Antigens in blood are carried by ___ to ___
APC’s to spleen`
51
Pathogens in other sites are transported in ___ to ____
Lymph to regional lymph node
52
Pathogens on musical surfaces are carried across mucosa and into ___ or ____
Tonsils or Peyers patches
53
Describe the steps in how T cells enter lymph nodes/leave HEV
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
Is LFA-1 and L-selectin present on lymphocyte or HEV
Lymphocyte
55
Is GlyCAM-1, ICAM-1 and CD34 on lymphocyte or HEV
HEV
56
Where are dendritic cells located
Throughout body
57
Where are macrophages located
Lymphoid tissue, connective tissue, body cavities
58
Where are B cells located
Lymphoid tissue, peripheral blood
59
What is the effect of activating dendritic cells
Results in activation of naive T cells
60
What is the effect of activating macrophages
Activate macropahges
61
What is the result of activating B cells
Delivery of help to B cells, antibody production
62
During rolling interaction and binding if T cell finds antigen what happens
Induce conformational change in LFA to increase binding affinity
63
What are the three signals for clonal expansion and differentiation in activating naive T cells
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
Despite self testing on T cells in thymus some make it through, peripheral cells and non-activate dendrites do not express
Co-stimulatory molecules and Naive T cells don’t get activated
65
Co-stimulatory signal alone, effect on T cell
No effect on T cell
66
Antigen specific signal alone effect on T cell
Inactivation (anergy) or deletion of T cell
67
If there is successful TCR:MHC binding what are the three survival transcription factors
NFAT, NFKB, AP1
68
What cytokine is synthesized to promote survival and activation of naive t Cells
IL-2
69
What does CD69 do
Retains stimulated T cell in lymph node for clonal differentiation and expansion
70
What is S1P
Chemoattractant that is high in the blood and low in tissues.
71
Do circulating naive T cells have high or low expression of S1P receptor
Low
72
T cells not stimulated by antigen ____S1PR1
Reexpress which allows naive T cells to respond to S1P gradient and exit lymphatic tissue
73
What happens when CD69 binds S1PR1
Cells internalized the complex and turn off S1PR expression, T cells in activation proliferate and differentiate and can’t leave
74
What retains naive T cell in lymph node
CD69
75
What causes proliferation of activated T cell
Express IL2 and IL2R via costimulatory signals with CD28
76
What cytokine is critical for differentiation of T cells into effector and memory cells
IL-2
77
Describe the steps in formation of IL-2R
Naive T cells express IL2 receptor gamma and betta, activation of these T cells leads to expression of alpha portion and induces proliferation
78
What does cyclosporine do
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
What is the ligand and receptor responsible for effector function of naive T cells
CD40 and CD40L
80
Describe the relationship between CD40, CD40L and T cells
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
What is Hyper IgM syndrome
CD40/CD40L deficiency that doesn’t allow antibody class switching, no activation of macrophages
82
what is CTLA-4
Inhibitory signal, binds B7 on APC to limit T cell proliferation, blocks CD28 signaling
83
What are short lived cells for immediate immune response
Effector T cells
84
what are long lived ells that respond to later infection with rapid, strong response, make new effector and memory cells
Memory cells
85
What must be produced in order to continue survival of memory T cells
IL-7
86
Describe steps of dendritic cell presenting to strong CD8+ T cell
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
Describe steps when dendritic cell presents signal to weaker CD8+ T cell
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
Once CD8+ Cells are activated how do they kill host cells
Apoptosis by releasing toxic granules
89
What toxic granules do cytotoxic T cells have
Perforin-pore forming protein that allow granzymes to enter which are serine proteases that activate capsases in host cells to trigger apoptosis
90
What cytokine produces Treg cells
TGF-B
91
what cytokine produces TfH cells
IL-6
92
What cytokines activate Th17
IL-6 and TGF-B
93
What cytokines activate TH1
INF-y and IL-12
94
What cytokine activate Th2
IL-4
95
What is the role of TH1
Control bacteria that grow in macrophages, express INF-y and IL-2
96
What is the role of Th2 cells
Control parasitic infection, express IL-4, IL-5, IL-13 that promote mast cells, eosinophils and B cell class switching to IgE
97
What is the role of Th17 cells
Stimulate neutrophil response to extracellular bacteria and fungi
98
What is the role of TfH cells
Stimulate antibody production from B cells including class switching and affinity maturation
99
What does Treg do
Regulate immune response
100
What bacteria can grow inside macrophage and phagosome, avoid detection by antibodies and CD8 T cells, inhibit fusion of phagosome and lysosome
Mycobacterium
101
What stimulates macrophage and boots antimicrobial mechanisms
IFN-y and CD40 ligand
102
What happens once macrophage is activated by TH1
Fusion of phagosome with lysosome and form reaction oxygen and nitrogen species
103
Why not always have macrophages activated
Energy costly and reactive oxygen and nitrogen species can cause damage to host cells and tissues
104
What drives Th2 cell differentiaiton
IL-4 in response to helminths and allergens
105
What happens when activate Th2 in response to helminths
Mast cells secrete IL-4,
106
What does IL-4 stimulate
B cell class switching to IgE
107
What does IL-5 activate
Eosinophils
108
What does IL-4 and IL-13 stimulate
Increased mucus secretion
109
What drives Th17 differentiation
Pro inflammatory cytokines and TGF-B
110
What does IL-17 do
Stimulates recruitment and production of neutrophils
111
What does IL-22 do
Promotes epithelial integrity, antimicrobial peptides and mucin
