Adaptive Immune responses; T cells

Question 1

What are the molecules that all T cells have?

Answer 1

CD4 and CD8

Question 2

When are CD4 and CD8 both expressed on T cells?

Answer 2

When they are immature.

Question 3

What does maturation of T cells involve?

Answer 3

The suppression of either CD4 or cD8

Question 4

Which T cells mainly have CD4?

Answer 4

T helper cells and T regulatory cells.

Question 5

Which T cell mainly have CD8?

Answer 5

Cytotoxic T cells

Question 6

How do T cells recognise antigen?

Answer 6

Via the TCR

Question 7

What is the structure of the TCR?

Answer 7

It is a heterodimer with alpha and beta chains, however a subgroup of T cells have heterodimer of gamma and delta chains. The TCR is antigen specific with a variable (V) and contstant (C) regions. The TCR does not recognise whole antigens, instead it recognises epitopes.

Question 8

Describe the structure of the TCR.

Answer 8

The variable region is most distal to the cell membrane and the constant region is most proximal. There is then a transmembrane sequence anchoring it to the plasma membrane with an intracellular carboxyl terminus.

Question 9

What do CD4/8 recognise?

Answer 9

part of the MHC that is constant in every individual for tissue compatibility. MHC-1 recognises CD8 and MHC-II recognises CD4

Question 10

What does the variable region of MHC do?

Answer 10

Holds the peptide antigen which is then presented to the TCR (MHC-II).

Question 11

What are the difficulties underlying cell signalling in T cells?

Answer 11

The short carboxyl tail does not have enough amino acids fro recognition by kinases, so the TCR has ITAMs (Immunoreceptor tyrosine-based activation motif) which is recognised by tyrosine kinases which phosphorylates the tyrosines, activating and initiating signalling in the cell.

Question 12

Name an example of a tyrosine kinase in T cells.

Answer 12

LCK (lymphocyte specific protein tyrosine kinase)

Question 13

Name the two sets of CD3 co-receptor complexes

Answer 13

CD3 molecules (3 types delta, gamma and epsilon. And homodimer zeta chains

Question 14

How are the variable regions of T cells created?

Answer 14

Through genetic recombination of TCR genes; randomly generated variability requires subsequent selection of T cells recognising the correct peptide-MHC combination i.e. the foreign peptide and self-MHC. Recognition of self-petides can occur.

Question 15

Where does the selection of T cells occur?

Answer 15

In the thymus; positive selection of the ability to recognise self-MHC
Negative selection for the recognition of peptides of self antigens.

Question 16

MHC-I in humans are which HLA?

Answer 16

A B and C

Question 17

MHC-II in humans are which HLA?

Answer 17

DP, DQ, DR

Question 18

What happens if when a T cell only recognises peptide-MHC?

Answer 18

It does not activate the T cell, it becomes functionally inactivated (anergy) and cannot elicit an immune response. Activation of T cells requires co-stimulation

Question 19

What are the co-stimulatory molecules of APCs?

Answer 19

B7 and ICAM; become expressed at higher levels in response to infection. These co-stimulatory molecules bind to receptors on the T cell surface; B7 - CD28 and ICAM-1 - LFA-1. This occurs alongside MHC-II - TCR

Question 20

How else can T cells become activated?

Answer 20

Through cytokines binding to cytokine receptors.

Question 21

What does activation cause T cells to do?

Answer 21

Proliferate, mediate effector functions and form memory cells, however most become effector cells.

Question 22

Mutual antagonism occurs between which T cells?

Answer 22

Th1 and Th2 to aid in differentiation of infections; bacterial or viral respectively.

Question 23

What does Th1 express and do?

Answer 23

Produces: IFN-gamma, IL-2 and TNF beta
Function: Aids Tcyt cells, macrophages and some B cells. Inhibits Th2 cells

Question 24

What does Th2 express and do?

Answer 24

Produces: IL-4/5/10/13
Function: aids B cell function and inhibits Th1

Question 25

What does Th17 express and do?

Answer 25

Il-17/22, promotes inflammation

Question 26

What does Tfh express and do? (follicular helper T cells

Answer 26

IL-21 and ICOS, helps activation of germinal centre of B cells through stimulating FDCs (2ndary lymphoid tissue)

Question 27

What do Treg express and do?

Answer 27

TGF-beta, IL-10/35, suppress immune response

Question 28

What do Tcyt express and do?

Answer 28

Perforin, granzymes, FasL for apoptosis, and cytokines. Kills infected cells

Question 29

Describe the process of T helper cell activating macrophages.

Answer 29

Th1 recognises pMHC on macrophage via TCR (specific recognition). CD40L on T cell binds to CD40 on macrophage also; costimulation. This causes the Th1 to produce IFNgamma. This combined activates tha macrophage for macrophage mediated microbiicidal killing where the respiratory burst is upregulated and also oxygen independent killing mechanisms.

Question 30

Describe the process of T helper cells activating CTLs

Answer 30

TCR - pMHC-II and CD40L-CD40 causes Th1 to secrete IL-1 and other cytokines, stimulating CTL. CTL activation can also occur via recognition of abnormal MHC-I on the dendritic cell by the TCR.

Question 31

Describe how CTLs kill an infected cells

Answer 31

Fas ligand pathway (death receptor-dependent killing); FasL binds to Fas on surface of infected target cell activating caspases.
Granzyme perforin pathway; perforin inserts pores into target cell membrane, granzymes can then be injected into the cell activating caspases.
Both processes activated caspases which initiate apoptosis.