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Infection and Immunity > Introduction to T Cells and the T Cell Receptor > Flashcards

Introduction to T Cells and the T Cell Receptor Flashcards

1
Q

What do T cells do?

A

Attack infected cells

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2
Q

What do B cells do?

A

Attack invaders outside the cells

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3
Q

How do T cells recognise pathogens from outside infected cells?

A

Antigen proteolysis inside the infected cell
Peptides presented on cell surface by MHC class 1 or 2 molecules

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4
Q

What recognises the MHC-peptide combination?

A

TCR

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5
Q

What happens after recoginition?

A

Activation of signalling processes inside the T cell leading to functional responses

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6
Q

What is the Listeria model?

A

From a study done in 1960s, used pathogen called listeria (lives inside macrophages) to investigate specific immunity
Involved adoptive transfer and in vitro reconstitution experiment

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7
Q

What is adoptive transfer?

A

Transfer of immune cells from an animal that has recovered from listeria to another animal not been infected yet to protect them from listeria
Adoptive transfer with serum failed to transfer specific immunity but T cell transfer was successful at protecting

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8
Q

What is in vitro reconstitution?

A

Macrophages infected with listeria - they die
If macrophages become activated by the infection and then T cells are added then very effective killing of listeria occurs
However, if macrophages not activated (by second signal) then killing of listeria not effective
Means that T cells work with something to kill pathogens

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9
Q

How do T cells activate macrophages?

A

Engagement of TCR with MHC on macrophage, activating effector T cell
Binding of CD40L and CD40
Release of IFN gamma which activated the macrophage
Secretion of cytokines, increased expression of MHC and costimulators, killing of phagocytosed bacteria

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10
Q

What is the nature of the cell-mediated immune response dependent on?

A

The pathogen

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11
Q

What does killing of listeria require?

A

T cells
Macrophages

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12
Q

What does killing of parasites require?

A

IgE
Eosinophils
Mast cells

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13
Q

What does killing of virally infected cells require?

A

Only T cells

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14
Q

What are the types of T cells?

A

Cytotoxic
Helper
Suppressor

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15
Q

What is MHC restriction?

A

T cells have to recognise both the peptide and MHC allele presenting it

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16
Q

Under what circumstances will the T cells recognise the antigens?

A

If it is presented by the self MHC

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17
Q

What would happen without the need for dual antigen/MHC recognition?

A

Toxic shock syndrome eg. caused by the staphylococcal syndrome toxin-1 which acts as a superantigen

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18
Q

What does the superantigen do?

A

Binds directly to both MHC class 2 and TCR, triggering multiple T cells to prod cytokines

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19
Q

Why do TCRs have a large range of specifities?

A

Highly variable amino acid sequence of the variable (Ag-binding) region

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20
Q

What is the structure of the TCR?

A

Highly variable antigen-binding domains attached to constant regions
TCR has only 1 binding site
TCRs do not bind native antigens but only processed peptides bound in the cleft of MHC-encoded proteins

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21
Q

What generates diversity?

A

Rearrangement of TCR genes (like Igs)

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22
Q

Where does TCR rearrangement occur?

A

In the thymus

23
Q

Why is junctional diversity prominent in TCR genes?

A

Insertion of non-coded bases and variation of joining site is more important in TCR than in Igs because there is no somatic hypermutation in TCR (Igs will continue to refine the antibody; does not happen in T cells)
Results in diverse a.a sequences in CDR3 loops which make contact with presented peptide

24
Q

What are T cells derived from?

A

Haematopoietic stem cells in BM

25
Q

Where do HSCs migrate to?

A

Thymus

26
Q

What do T cells become?

A

CD4+ or CD8+

27
Q

Where do naive T cells migrate to?

A

Secondary lymphoid tissue

28
Q

What do naive T cells interact with?

A

Peptides presented on MHC molecules by APCs

29
Q

What occurs upon productive interaction with a T cell?

A

Clonal selection
Amplification of T cell

30
Q

What happens to selected and amplified T cells?

A

Leave the lymph nodes and target infected tissues

31
Q

Where is the T cell repertoire selected and how ?

A

In the thymus
T-cell precursors travel from BM to develop in the thymus

32
Q

What are double negative T cells?

A

Newly arrived cells in the thymus (early thymic progenitor cells)
CD4- CD8-
Do not express TCR

33
Q

What happens to the double negative cells?

A

Upregulate CD25 (IL-2 receptor) and RAG1 & RAG2
Rearrange TCR-beta locus

34
Q

What happens after rearrangement of TCR-beta?

A

T cells express an invariant alpha chain called pre-T alpha alongside the TCR beta gene
If rearranged beta chain successfully pairs with the invariant alpha chain, signals are produced, ceasing rearrangement of beta chain
Pre-TCR forms and cells undergo a round of proliferation
Rearrangement of TCR-alpha locus
Pre-TCR signals the cells to transcribe the genes for CD4 and CD8
CD4+ CD8+ cells produced = double positive

35
Q

What are the 3 classes of TCRs produced?

A

Potentially useful in interacting with foreign pathogens
Do not interact with anything
Potentially harmful, react with self antigens

36
Q

What happens to the double positive cells?

A

Migrate deep into thymic cortex and are presented with self-antigens
Self antigens expressed by thymic cortical epithelial cells (CTECs) on MHC molecules on cell surface

37
Q

Which cells receive survival signals?

A

Only those that interact with MHC-I or MHC-II

38
Q

When is the TCR first expressed for AB T cells?

A

During development in the thymus

39
Q

What is the purpose of negative T cell selection ?

A

Elimination of self-reactive cells

40
Q

What is the purpose of positive selection?

A

To select for cells with TCRs capable of interacting with self-MHC

41
Q

What is death by neglect?

A

Cells that do not interact strongly enough with MHC peptide complexes will die (no survival signal)
Ensures that selected T cells will have MHC affinity that will serve useful functions in the body

42
Q

What happens to DP cells that interact with MHC II?

A

Become CD4+ by downregulation of CD8 surface receptors

43
Q

Where does negative selection occur?

A

In the thymic medulla thymocytes are presented with self-antigen on MHC of medullary thymic epithelial cells (mTECs)

44
Q

What happens to thymocytes that interact too strongly with the self-antigen?

A

Receive apoptotic signal leading to cell death
Some are selected to become Treg cells

45
Q

Under what circumstances does negative selection work?

A

If it can eliminate self antigens expressed in all tissues - but the thymus is a specialised tissue so cannot do this
Solved by mTECs expressing transcription factor AIRE - allows promiscuous expression of self antigens from all tissues of the body on MHC I

46
Q

What problem remains regarding negative selection?

A

How to negatively select T cells that recognise self antigens expressed on MHC II
Solved by thymic dendritic cells which can phagocytose mTECs - allowing for presentation of self-antigens on MHC II

47
Q

What attracts naive T cells into the lymph nodes?

A

Chemokine receptor CCR7 on T cell recognises CCL21 prod by specialised blood vessels called high endothelial venules (HEV)
CCR7 also recognises CCL19 prod by DCs in the lymph node

48
Q

How do T cells enter the lymph node?

A

L selectin on naive T cell induces rolling
Chemokine CCL21 recognition activates integrins to enhance their binding
T cell continues to follow chemokine gradient into lymph node

49
Q

What happens to T cells that do not encounter their antigen?

A

Re-enter blood and continue circulating

50
Q

How are effector T cells guided to sites of infection?

A

By chemokines and newly expressed adhesion molecules

51
Q

What happens when naive T cells become effector T cells?

A

Cease production of L-selectin
Express VLA-4, which recognises VCAM-1
VCAM-1 found on activated vascular endothelium when inflammation is triggered

52
Q

How do T cells find their targets?

A

By cell adhesion
Non specific adhesion proteins allow initial binding to potential targets
If target has correct antigen/MHC combination, TCR signalling occurs
Induces conformational change in adhesion proteins which strengthens binding
Focused release of effector molecule

53
Q

Describe gamma delta T cells

A

2 distinct chains forming gamma delta heterodimer
Less variable than convention ab TCR
Together with CD3 may play a role in innate immunity
Found in peripheral sites (skin, lung, intestine, liver)

Infection and Immunity (33 decks)

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