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Core Concepts in Immunology > Lecture 12. T-cell Activation and Differentiation > Flashcards

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
Q

What is the function of CD4 ?

A

Signal transduction

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26
Q

What is the function of CD8 ?

A

Signal transduction

27
Q

What is the function of CD28 ?

A

Signal transduction (costimulation )

28
Q

What is the function of CTLA-4 ?

A

Negative regulation

29
Q

What is the function of LFA-1 ?

A

Adhesion signal transduction

30
Q

What is the function of VLA-4 ?

A

adhesion signal transduction

31
Q

What forms the T cell signalling complex ?

A

The TCR, CD3 an TCR zeta

32
Q

How many polypeptide chains is CD3 made from ?

A

3

33
Q

What are the immunoreceptor tyrosine-based activation motifs ?

A

Regions of signaling proteins phosphorylated on tyrosine residues and become docking sites for other signaling molecules

34
Q

What is the immunological synapse ?

A

Contact between effector T cell and target

35
Q

What does SMAC stand for ?

A

Supra molecular adhesion complex

36
Q

What does antigen recognition by T cells induce ?

A

Early signalling events

37
Q

What are the early signalling events induced by antigen recognition by T-cells ?

A
  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
Q

What are the roles which cytokines have in T cell responses ?

A
  1. T cell homeostasis
  2. Clonal expansion
  3. T cell differentiation
  4. Effector functions
39
Q

What is the IL2 receptor complex made up of ?

A

Beta and gamma c chains.

40
Q

What does the gamma c designate ?

A

Common gamma chain

41
Q

What happens to low affinity IL2 receptor on activation ?

A

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
Q

What is often used as a T cell activation marker ?

A

CD25

43
Q

What happens when a resting naive CD8 T cell engages its specific MHC I peptide complex displayed on the surface of a fibroblast ?

A

Becomes anergic

44
Q

What are the functions of CD4 T cells ?

A
  1. Cell mediated immunity
  2. Humoral immunity
45
Q

What is the function of cell mediated immunity ?

A

Provide cytokines to CD8 T cells to help in cytotoxicity

46
Q

What is the function of humoral immunity ?

A

Provide signals and cytokines to activate B cells to produce antibody

47
Q

What is the signature cytokine of Helper T cell 1 ?

A

IFN gamma

48
Q

What are the signature cytokines of helper T cell 2 ?

A
  1. IL4
  2. IL5
  3. IL13
49
Q

What are the signature cytokines of helper T cell 17 ?

A
  1. IL17A
  2. IL17F
  3. IL22
50
Q

What are the immune reactions of helper T cell 1 ?

A
  1. Macrophage activation
  2. IgG prioduction
51
Q

What are the immune reactions of helper T cell 2 /

A
  1. Mast cell, eosinophil activation
  2. IgE production
  3. Alternative macrophage activation
52
Q

What are the immune reactions of helper T cell 17 ?

A

Neutrophilic monocytic inflammation

53
Q

What is the host defense of helper T cell 1 ?

A

Intracellular microbes

54
Q

What is the host defense of helper T cell 2 ?

A

Helminthic parasite

55
Q

What is the host defense of helper T cell 17 ?

A

Extracellular bacteria and fungi

56
Q

What is role in disease of helper T cell 1 ?

A
  1. Autoimmune diseases
  2. tissue damage associated with chronic infections
57
Q

What is the role in disease of helper T cell 2 ?

A

Allergic diseases

58
Q

What is the role in disease of helper T cell 17 ?

A

Autoimmune and inflammatory diseases

59
Q

What is signal 3 for T cell differentiation provided by ?

A

Cytokines produced by the activated antigen presenting cell

60
Q

What are the polarisin cytokines produced by dendritic cells depend on ?

A

Which pathogen recognition receptors were activated by the microbe

61
Q

What do class I and class II cytokine receptors signal via and why ?

A

Receptor associated kinases to activate specific transcription factors

62
Q

What happens after activation by an antigen and costimulators to naive helper T cells ?

A

They may differentiate into different subsets under the influence of cytokines produced at the site of activation

63
Q

What is TH17 differentiated by ?

A

TGF-beta

64
Q

What are the major transcription factors involved in helper T cell differentiation ?

A
  1. T-beta - TH1 cells
  2. GATA-3 -TH2 cells
  3. RORgammaT - TH17

Core Concepts in Immunology (22 decks)

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