4. Adaptive Immune Response: T Cells

Question 1

How do T cells recognise antigen? Which CD molecules can this associate with?

Answer 1

T cell receptor (TCR), CD4 or CD8

Question 2

Where do T cells develop?

Answer 2

Thymus (grow in bone marrow like every other cell, then move and develop in thymus)

Question 3

What happens when T cells become mature?

Answer 3

Will either become CD4+ or CD8+

Question 4

What do most CD4+ T cells do?

Answer 4

Helper T cells (help other immune system cells to carry out function) or regulatory T cells (suppress unwanted immune responses)

Question 5

What do most CD8+ T cells do?

Answer 5

Cytotoxic T Cells (cytotoxic)

Question 6

What are the two versions of T Cell receptor?

Answer 6

(most are) alpha-beta TCR (Alpha and beta chains), may also be gamma-delta TCR (lesser)

T cells may be one or the other of these

Basically all T cells are alpha-beta

Question 7

What is the structure of the TCR?

Answer 7

Heterodimer (alpha and beta chains), each with a variable and constant region

Variable region gives T cell specificity - recognises particular peptide-MHC combination
Constant region
Transmembrane segment
Short cytoplasm tail

Question 8

How are the domains of the TCR stabilised?

Answer 8

Intrachain disulphide bond, chains linked together by interchain disulphide bond

Question 9

How do MHCs vary between individuals?

Answer 9

Bits that vary are in the groove that binds the peptide, other bits do not vary between individuals (non-polymorphic)

Question 10

What part of the MHC does CD4/8 bind?

Answer 10

The non-polymorphic side (non varying part)

Question 11

What MHC does CD8 bind to and which does CD4 bind to?

Answer 11

CD8 - MHCI
CD4 - MHCII

No exception

Question 12

How do TCRs send signals into the cell?

Answer 12

Through the CD3 coreceptor complex (CD3delta, epsilon gamma and zeta chain)

ITAMs on the zeta chains are phosphorylated by Lck causing a signalling cascade which ends up in T cell activation (only if co-stimulation occurs)

There is antigen specificity of the TCR

Question 13

What is an ITAM?

Answer 13

Immunoreceptor tyrosine based activation motif - present on the CD3 co-receptor complex

Question 14

How is variability of TCRs created?

Answer 14

Unique genetic recombination of TCR genes (only found in lymphocytes)

Question 15

What occurs to the TCRs/T cells after genetic recombination? What are the two forms of selection?

Answer 15

Selection occurs in the thymus (checking that T cells are useful)

Positive selection - check that our T cell receptors recognise own MHC version

Negative selection - check if recognise foreign peptides

Question 16

What happens if you only send a signal through the CD3 and TCR?

Answer 16

Inactivation of T lymphocyte - Anergy

Question 17

What co-stimulation is required to activate T cell?

Answer 17

Additional interactions e.g. CD80 and CD86 molecules

Question 18

What additional co-stimulation of T cells may occur?

Answer 18

Through cytokines leads to additional co-stimulation

Question 19

What happens when T Cell is activated (3)?

Answer 19

Proliferate and expand in number, carry out effector function (e.g. kill cells), form memory cells

Question 20

What are the various types of helper T Cell? What do they express?

Answer 20

Th1 cell - produce cytokines such as interferon gamma, interleukin 2 and TNF beta - involved in helping cytotoxic T lymphocytes/ macrophages to carry out functions, help B cells produce antibody, inhibit Th2 cells

Th2 cell - produce IL-4, 5, 10, 13 - specialised in making B cells make antibody, inhibit Th1

Th17 cell - produce IL-17, 22

Tfh - produce IL-21 and ICOS - help B cells produce antibody in germinal centres in secondary lymphoid tissues

Question 21

Describe CD4 Treg and CD8 Tc

Answer 21

Treg: produce TGFbeta, IL-10, 35 - suppress unwanted immune response

Tc: produce perforin, granzymes, fas ligand - kill infected cells

Question 22

What are the co-stimulatory molecules of the Th1 cell?

Answer 22

CD86, CD28, CD40 - activates Th1 cell causing secretion of gamma interferon which in turn superactivates macrophages

Question 23

How do helper T cells help cytotoxic T cells?

Answer 23

Th1 secrete IL-6, 2 which activate cytotoxic T cell

Question 24

How do cytotoxic T lymphocytes (CTL) kill cells?

Answer 24

2 mechanisms - identical to NK cells

Fas/Fas-ligand pathway - Fas-ligand of CTL binds to Fas

Granzyme pathway - release of granzymes and perforin (similar to C9) - perforin makes pores to insert granzymes

Net result of either pathway is activation of caspases which set off programmed cell apoptosis destroying the infected cell to be taken up by phagocytic macrophages