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MIIM30002 > Lecture 20: Early Lymphocyte Maturation - T cells > Flashcards

Lecture 20: Early Lymphocyte Maturation - T cells Flashcards

1
Q

Where do T lymphocytes develop?

A

in the thymus

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2
Q

What does activation of TCR require?

A

interaction with major histocompatibility complexes (MHC)

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3
Q

What do T lymphocytes express?

A

CD4 or CD8 co-receptors

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4
Q

What are the effector functions of T cells?

A

involves direct killing (cytotoxic) or secretion of cytokines (helper)

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5
Q

What are the similarities of T cell and B cell development?

A

stepwise rearrangement of receptors
have to undergo strict controls of testing
eventual assembly of the heterodimeric receptor

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6
Q

What are the differences of T cell and B cell development?

A

two distinct sets of TCRs
more diverse subsets
MHC restriction
produced only in the first decade or so

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7
Q

Where is the thymus and what is it made up of?

A

just above the heart

made up of thymic stroma cells crucial for function

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8
Q

What do conditions affecting the thymus have major implications on?

A

development of immune responses

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9
Q

What are examples of thymic stroma cells?

A

intrathymic dendritic cells, macrophages and thymic epithelial cells

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10
Q

What is the thymus segregated into?

A

the cortex and medulla

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11
Q

What are characteristics of the cortex?

A

more densely pack; peripheral

mostly immature thymocytes

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12
Q

What are characteristics of the medulla?

A

less packed; central

site for negative selection - DC generally absent from cortex

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13
Q

What does successful maturation of thymocytes lead to (if they do not undergo apoptosis like the majority)?

A

successful maturation leads to formation of αβ T cells, γδ T cells and invariant T cells (e.g. NKT)

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14
Q

What are the stages of thymocyte maturation?

A

there are double negative (DN) and double positive (DP) stages
DNs can be classified into four distinct stages

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15
Q

What can DN cells give rise to?

A

all three subsets

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16
Q

What do CLPs that enter the thymus interact with?

A

TECs through Notch1

17
Q

What are characteristics of DN1 thymocytes?

A

classified as DN1 shortly after entering through HEV and Notch signalling
germline configuration of TCR genes
CD44+ CD25-

18
Q

What are characteristics of DN2 thymocytes?

A

undergo routing to the cortex and become responsive to IL-2
CD44+ CD25+
starts rearranging beta chain of TCR

19
Q

What are characteristics of DN3 thymocytes?

A

joining of DJ-beta to V-beta -> if unsuccessful remains in this stage and dies shortly after
pairing of beta chain with a surrogate alpha chain to form the pre-TCR
CD44 low CD25+

20
Q

What are characteristics of the pre-TCR?

A

analogous with pre-BCR, forms complex with CD3 chains, signalling stops beta chain rearrangement and promotes allelic exclusion, induces cell proliferation

21
Q

What are characteristics of DN4 thymocytes?

A

rapid cell proliferation occurs
induction of CD4 and CD8
represses RAG-1 and RAG-2
CD44- CD25-

22
Q

What are characteristics of DP thymocytes?

A

able to start rearranging alpha chain
capable of successive V alpha and J alpha rearrangements
express both CD4 and CD8
requires + selection to shut off rearrangement and progression of maturation

23
Q

What is the role of positive selection?

A

tests the ability of DP cells to recognise MHC molecules

DP cells that do not receive signals from + selection die from neglect

24
Q

What does positive selection coordinate?

A

the expression of CD4 or CD8

binding of MHC I promotes CD8 T cells and binding of MHC II promotes CD4 T cells

25
Q

What does strength of TCR binding to MHC dictate?

A

subsequent activation in the periphery

26
Q

Where does negative selection occur?

A

can occur in both cortex and medulla but predominantly in the latter

27
Q

What is negative selection important for?

A

the removal of self reactive cells

28
Q

Recognition of specific MHC:peptide complex in the ____ leads to ____ while in the ____ leads to ____.

A

thymus, deletion

periphery, activation

29
Q

What is the role of thymic cortical epithelial cells?

A

express MHC important in positive selection

30
Q

What is the role of medullary epithelial cells and DCs?

A

express autoimmune regulator (AIRE) which facilitates negative selection

31
Q

What do interactions of thymocytes with thymic stromal cells facilitate?

A

selection

32
Q

What happens to T cells which are just on the threshold of having binding that is too strong in the thymus?

A

conversion / commitment of cells to regulatory T cells
a small population can form iNKT cells that bind CD1 molecules
some escape to the periphery and can be rendered anergic or tolerogenic

33
Q

What do thymocytes require to survive?

A

rescue by positive signals

MIIM30002 (25 decks)

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