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Immunology and Virology > Week 12 > Flashcards

Week 12 Flashcards

1
Q

Where do T cells develop?

A

In the thymus

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2
Q

Where is the thymus situated?

A

Upper anterior thorax

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3
Q

What are the four key regions of the thymic lobule involved in T cell development?

A

Corticomedullary junction (CMJ)
Cortex
Sub capsular zone
Medulla

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4
Q

Give brief overview of the stages on thymic development

A 
Progenitor cells migrate into thymic parenchyma
Double negative selection
Become double positive cells
Negative selection
Positive selection
Differentiate into single positive CD4+ or CD8+ cells
Central tolerance
Mature thymocytes re-enter vasculature
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5
Q

Entry of progenitor cells into the CMJ is regulated by what?

A

Adhesive interactions by PSGL1 on progenitor cells and P-selectin on thymic epithelium cells
(PSGL1 = platelet selecting protein ligand 1)

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6
Q

What is the first stage of T cell development once the progenitor cells have entered the thymus?

A

Double negative selection

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7
Q

Which chemokines regulate migration of the DN thymocytes to the outer region of the cortex?

A

CXCR4 - CXCL12
CCR7 - CCL19
further migration CCR9 - CCL25

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8
Q

During the DN migration, what happens to the thymocytes?

A

Begin to assemble a pre-TCR complex

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9
Q

Formation of the pre-TCR complex leads to which 3 things?

A

Initiation of proliferation
Signalling for thymocytes to become double positive (have both CD4 and CD8)
Signalling for completion of TCR complex

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10
Q

DP thymocytes developed in the outer space are ______

A

Dp thymocytes developed in the outer space are MOTILE

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11
Q

What are DP thymocytes able to do?

A

Interact with MHC complexes on cortical thymic epithelial cells via their TCR

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12
Q

Interaction of DP thymocyte TCRs with cortical thymic epithelial cell MHC complexes leads to what?

A

Positive and negative selection

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13
Q

What happens in negative selection of T cells?

A

High-affinity signals –> deletion of thymocytes by apoptosis
No signals from TCR –> death by neglect

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14
Q

What happens in the positive selection of thymocytes?

A

DP thymocytes are induced to receive signals for survival via low affinity interactions

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15
Q

Thymocytes which successfully survive positive and negative selection do what?

A

Gain expression of CCR7

Differentiate into single positive CD4+ or CD8+ cells

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16
Q

Once thymocytes have differentiated into single positive cells, where do they migrate to and roughly how long do they spend there?

A

The medulla, 12 days

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17
Q

Once thymocytes have differentiated into single positive cells, what is the final selection stage they undergo?

A

Central tolerance

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18
Q

Describe central tolerance

A

Occurs in the medulla
DCs display self Ags provided to them by AIRE+ mTECs
-ve selection - Tissue specific Ag reactive T cells are deleted
+ve selection - Treg cells generated

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19
Q

Generally, in which part of the thymus are the immature thymocytes found in?

A

Cortex

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20
Q

Generally, which part of the thymus are the mature thymocytes in?

A

Medulla

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21
Q

How many classes of TCR are there?

A

2

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22
Q

What are the two classes of TCR?

A

⍺β (majority -95%)

λδ

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23
Q

Which TCR class is found in the majority of T cells?

A

⍺β (≈95%)

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24
Q

In T cell activation, APCs deliver 3 kinds of signals to naive T cells. What are they?

A

1 - activation. Recognition of MHC complex
2 - survival. B7-CD28 co-stimulation
3 - differentiation. Production of cytokines by the APCs which will dictate the functional profile of the T cell

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25
Q

Like Abs, TCRs have variable and constant regions. Do they recognise Ags by similar functions as well?

A

No - recognise by fundamentally different functions!

Although Fab region is structurally similar, have number of key differences

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26
Q

How are CD3 and the TCR linked?

A

TCR relies on CD3 for intracellular signalling (cannot do by itself)

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27
Q

What is the CD3 complex?

A

Found on all* T cells, collection of 4 membrane signalling chains (2 ε, 1 δ and 1 γ )that are associated with the TCR to allow intracellular signalling (recognition of Ag binding). Associated with an interior homodimer of 2 ζ chains. Each CD3 chain has 1 ITAM (ζ has 3)

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28
Q

What is the key function of Th1 CD4+ cells?

A

Activate macrophages, help them to suppress intracellular infections

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29
Q

What is the key function of Th17 CD4+ cells?

A

Enhance neutrophil response to fungal and extracellular bacterial infections

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30
Q

What is the key function of Th2 CD4+ cells?

A

Activate cellular and Ab response to parasites

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31
Q

What is the key function of Tfh CD4+ cells?

A

Activate B cells
Switch isotype
Maturation of Ab response (increase Ab affinity)

32
Q

What is the key function of Treg CD4+ cells?

A

Suppress other effector T cells

33
Q

IL-12 and IFN-γ induce CD4+ cells into which functional state?

A

Th1

34
Q

IL-6, TGF-β and IL-23 induce CD4+ cells into which functional state?

A

Th17

35
Q

IL-4, IL-2 and IL-33 induce CD4+ cells into which functional state?

A

Th2

36
Q

IL-6, IL-21 and ICOSL induce CD4+ cells into which functional state?

A

Tfh

37
Q

TGF-β and IL-2 induce CD4+ cells into which functional state?

A

Treg

38
Q

Which cytokines induce CD4+ cells into Th1 functional state?

A

IL-12

IFN-γ

39
Q

Which cytokines induce CD4+ cells into Th2 functional state?

A

IL-4
IL-2
IL-33

40
Q

Which cytokines induce CD4+ cells into Th17 functional state?

A

IL-6
TGF-β
IL-23

41
Q

Which cytokines induce CD4+ cells into Tfh functional state?

A

IL-6
IL-21
ICOSL

42
Q

Which cytokines induce CD4+ cells into Treg functional state?

A

TGF-β

IL-2

43
Q

What is the defining TF for Th1?

A

T-bet

44
Q

What is the defining TF for Th2?

A

GATA3

45
Q

What is the defining TF for Th17?

A

ROR-γ

46
Q

What is the defining TF for Tfh?

A

Bcl6

47
Q

What is the defining TF for Treg?

A

FoxP3

48
Q

What are the major cytokines released by Th1?

A

IFN-γ
IL-2
TNF
(minor = LT, GM-CSF, IL-3)

49
Q

What are the major cytokines released by Th2?

A 
IL-4
IL-5
IL-6
IL-13
(minor IL-10, IL-3, GM-CSF)
50
Q

What are the major cytokines released by Th17?

A

IL-17A
IL-21
IL-22
(minor IL-17F, TNF)

51
Q

What are the major cytokines released by Tfh?

A

IL-4
IL-21
CD40L

52
Q

What are the major cytokines released by Treg?

A

IL-10
TGF-β
IL-35

53
Q

IFN-γ, IL-2 and TNF are the major cytokines released by which CD4+ effector cell?

A

Th1

54
Q

IL-4, IL-5, IL-6 and IL-13 are the major cytokines released by which CD4+ effector cell?

A

Th2

55
Q

IL-17A, IL-21 and IL-22 are the major cytokines released by which CD4+ effector cell?

A

Th17

56
Q

IL-4, IL-21 and CD40L are the major cytokines released by which CD4+ effector cell?

A

Tfh

57
Q

IL-10, TGF-β and IL-35 are the major cytokines released by which CD4+ effector cell?

A

Treg

58
Q

What do CD8+ T cells differentiate into?

A

Cytotoxic T lymphocytes (CTLs)

59
Q

CD8+ T cells/CTLs are important in the defence of ___

A

intracellular pathogens, such as virus infected cells or tumours

60
Q

True or false - CD8 cells form stable, permanent binding which the first thing they bind to

A

FALSE. CD8 cells will bind transiently with nonspecific adhesion molecules (LFA-1 to ICAM). For the binding o stabilise, there must be Ag specific interaction, otherwise the cells will, separate

61
Q

CD8 cells will initially bind to cells via what?

A

Nonspecific adhesion molecules, LFA-1 and ICAM

62
Q

What are the 3 most important cytotoxic effector molecules released by CD8+/CTLs?

A

Perforin
Granuzymes
Granulysin

63
Q

What action does perforin have on target cells?

A

Aids delivery of granule contents into cytoplasm of target cell

64
Q

What are granuzymes and what action do they have on target cells?

A

= serine proteases

Activate apoptosis once in the cytoplasm of the target cell

65
Q

What action does granulising have on target cells?

A

Has antimicrobial actions and can induce apoptosis

66
Q

The thymic cortex has a large population of macrophages in addition to the developing T cells. These particularly macrophages are useful for what?

A

Engulfing apoptotic thymocytes

67
Q

What does HSCT stand for?

A

Haematopoietic stem cell transplant

68
Q

Where can haematopoietic stem cells be sourced from? (3)

A

Bone marrow
Peripheral blood
Umbilical cord blood

69
Q

Infused haematopoietic stem cells have a unique property. What is it?

A

Able to hone to the bone marrow niche

70
Q

A mixed lymphocyte reaction is an example of a method that can be used for HLA compatibility. How does it work?

A

Donor cells irradiated to prevent proliferation - act as stimulator cells
Recipient cells act as responder cells.
Alloreactive T cells of the patient will be activated
Co-culture cells for 3-4 days, then measure proliferation and capacity of recipient cells to kill donor cells

71
Q

What is Graft versus Host Disease (GvHD)?

A

Where donor graft attacks recipient (opposite of graft rejection)

72
Q

Disparities between what are the main cause of GvHD?

A

Disparities between minor HLAs are the main cause (are matched for majors)

73
Q

Which HLA types are HSCT recipient/donors matched for?

A

HLA-A, B, C and DR

74
Q

Acute GvHD has many features of which disorders?

A

Th1 disorders, inflammatory diseases

75
Q

Chronic GvHD is characterised by what?

A 
Epithelial injury
Immune infiltration
Fibrosis
Mostly Th2 driven
(resembles autoimmune disorders)

Immunology and Virology (6 decks)

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