Lecture 12. T-cell Activation and Differentiation Flashcards

1
Q

What is one of the first things that T-cells do ?

A

Produce IL2

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2
Q

What is the induction of response in cell mediated immunity ?

A

Naive CD4+ T-cells and CD8+ T-cells recognise peptides and that are derived from protein antigens and presented by antigen-presenting cells in peripheral lymphoid organs. The T-lymphocytes are activated to proliferate and differentiate into effector cells ehich enter the circulation

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3
Q

Where do effecter T-cells go ?

A

The site of the antigen

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4
Q

How do effector T-cells travel ?

A

They migrate through blood vessels in peripheral tissues by binding to endothelial cells

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5
Q

What are endothelial cells activated by ?

A

Cytokines

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6
Q

What are T-cell effector functions ?

A

CD4+ T-cells recruit and activate phagocytes to destroy microbes and CD8+ cytotoxic T lymphocytes kill infected cells

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7
Q

What are the steps in activation of T-cells ?

A
  1. Antigen recognition
  2. Activation
  3. Clonal expansion
  4. Differentiation
  5. Effector functions
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8
Q

How do T-cells respond to antigen recognition ?

A

By producing cytokines and expressing receptors for these cytokine leading to an autocrine pathway of cell proliferation resulting in clonal expansion

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9
Q

What does naive T-cell activation require ?

A

Two signals

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10
Q

What are the two signals that naive t-cell activation requires ?

A
  1. T-cell receptor
  2. Co-stimulatory molecules
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11
Q

What is the purpose of requiring two signals for naive T-cell activation ?

A

Ensures only appropriate activation occurs - microbes induce expression of signal 2 so full T cell activation should only occur in presence of infection

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12
Q

What does the co-stimulatory molecule B7 do ?

A

Binds CD28 on the naive T cell

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13
Q

What does CTLA-4 provide and why ?

A

Negative signals to help regulate T-cell responses

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14
Q

What does CTLA-4 binding to B7 achieve ?

A

Inhibitory signals to activated T- cells

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15
Q

What may present peptide antigens, but do not express costimulators and are unable to activate naive T-cells ?

A

Resting antigen presenting cells which have not been exposed to microbes or adjuvants

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16
Q

What may T cells that recognise antigen without costimulation become ?

A

Tolerant to subsequent exposure to the antigen (anergy

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17
Q

What induces the expression of costimulators on the antigen presenting cells ?

A

Microbes as well as cytokines produced during the innate immune responses

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18
Q

What happens once a naive T cell has been properly activated ?

A

Undergoes prolliferation/clonal expansion

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19
Q

What is initital activation of naive T cells ?

A

An important checkpoint

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20
Q

How do naive CD8+ T cells become activated if MHC class I presenting cells dont express costimulatory molecules ?

A

Cross presentation

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21
Q

What is cross presentation needed for ?

A

Activation of naive CD8+ T-cells

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22
Q

How is cross presentation thought to occur ?

A

By cytosolic diversion

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23
Q

What is cytosolic diversion ?

A

Where proteins are transported out of phagosomes into the cytosol and then enter the class I pathway as usual

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24
Q

What is the function of CD3 ?

A

Signal transduction by TCR complex

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25
What is the function of CD4 ?
Signal transduction
26
What is the function of CD8 ?
Signal transduction
27
What is the function of CD28 ?
Signal transduction (costimulation )
28
What is the function of CTLA-4 ?
Negative regulation
29
What is the function of LFA-1 ?
Adhesion signal transduction
30
What is the function of VLA-4 ?
adhesion signal transduction
31
What forms the T cell signalling complex ?
The TCR, CD3 an TCR zeta
32
How many polypeptide chains is CD3 made from ?
3
33
What are the immunoreceptor tyrosine-based activation motifs ?
Regions of signaling proteins phosphorylated on tyrosine residues and become docking sites for other signaling molecules
34
What is the immunological synapse ?
Contact between effector T cell and target
35
What does SMAC stand for ?
Supra molecular adhesion complex
36
What does antigen recognition by T cells induce ?
Early signalling events
37
What are the early signalling events induced by antigen recognition by T-cells ?
1. Tyrosine phosphorylation of molecules of T cell receptor which phosphorylate ITAMs on CD3zeta 2. Zap70 associates an becomes phosphorylated 3. Zap70 then phosphorylates adapter proteins that trigger P13K, PLC and Ras
38
What are the roles which cytokines have in T cell responses ?
1. T cell homeostasis 2. Clonal expansion 3. T cell differentiation 4. Effector functions
39
What is the IL2 receptor complex made up of ?
Beta and gamma c chains.
40
What does the gamma c designate ?
Common gamma chain
41
What happens to low affinity IL2 receptor on activation ?
The cells produce IL2 and express the alpha chain of the IL2R which associates with the beta and gamma c chains to form the high affinity IL2 receptor
42
What is often used as a T cell activation marker ?
CD25
43
What happens when a resting naive CD8 T cell engages its specific MHC I peptide complex displayed on the surface of a fibroblast ?
Becomes anergic
44
What are the functions of CD4 T cells ?
1. Cell mediated immunity 2. Humoral immunity
45
What is the function of cell mediated immunity ?
Provide cytokines to CD8 T cells to help in cytotoxicity
46
What is the function of humoral immunity ?
Provide signals and cytokines to activate B cells to produce antibody
47
What is the signature cytokine of Helper T cell 1 ?
IFN gamma
48
What are the signature cytokines of helper T cell 2 ?
1. IL4 2. IL5 3. IL13
49
What are the signature cytokines of helper T cell 17 ?
1. IL17A 2. IL17F 3. IL22
50
What are the immune reactions of helper T cell 1 ?
1. Macrophage activation 2. IgG prioduction
51
What are the immune reactions of helper T cell 2 /
1. Mast cell, eosinophil activation 2. IgE production 3. Alternative macrophage activation
52
What are the immune reactions of helper T cell 17 ?
Neutrophilic monocytic inflammation
53
What is the host defense of helper T cell 1 ?
Intracellular microbes
54
What is the host defense of helper T cell 2 ?
Helminthic parasite
55
What is the host defense of helper T cell 17 ?
Extracellular bacteria and fungi
56
What is role in disease of helper T cell 1 ?
1. Autoimmune diseases 2. tissue damage associated with chronic infections
57
What is the role in disease of helper T cell 2 ?
Allergic diseases
58
What is the role in disease of helper T cell 17 ?
Autoimmune and inflammatory diseases
59
What is signal 3 for T cell differentiation provided by ?
Cytokines produced by the activated antigen presenting cell
60
What are the polarisin cytokines produced by dendritic cells depend on ?
Which pathogen recognition receptors were activated by the microbe
61
What do class I and class II cytokine receptors signal via and why ?
Receptor associated kinases to activate specific transcription factors
62
What happens after activation by an antigen and costimulators to naive helper T cells ?
They may differentiate into different subsets under the influence of cytokines produced at the site of activation
63
What is TH17 differentiated by ?
TGF-beta
64
What are the major transcription factors involved in helper T cell differentiation ?
1. T-beta - TH1 cells 2. GATA-3 -TH2 cells 3. RORgammaT - TH17