T cell effector functions and the MHC

Question 1

Which T cells are depleted in HIV/AIDS?

Answer 1

CD4+ T cells

Question 2

Define MHC restriction.

Answer 2

T cells recognise pathogens by recognising pathogenic peptide fragments on MHC molecules. They can not recognise whole antigen, only a combination of antigen peptide with MHC.

Question 3

Describe the structure of MHC molecules.

Answer 3

MHC molecules are transmembrane proteins that contain a specific peptide binding groove to which the pathogenic peptide is held in for presentation to T cells.

MHC class I is expressed on all nucleated cells.

MHC class I consists of 3 alpha subunits and 1 Beta-2 microglobulin.

MHC class II is expressed on APCs such as Monocytes/Macrophages, Dendritic cells and B cells.

MHC class II consists of 2 alpha subunits and 2 beta subunits Disulphide bonds

Question 4

Give an example of a human body cell that does not express MHC Class I.

Answer 4

Erythrocytes - Lack a nucleus

Question 5

Where are the genes that encode both classes of MHC found?

Answer 5

On the short arm of chromosome 6.

Question 6

How many polymorphic genes are involved in encoding an MHC class I molecule?

Answer 6

There are 3 HLA genes:

HLA-A, HLA-B and HLA-C

Question 7

Describe the structure of the TCR.

Answer 7

Heterodimer of either alpha-beta or gamma-delta subtypes.

Consist of variable and constant domains

V-alpha, C-alpha, V-beta, C-beta

Question 8

How many different genes make up the light chain of the TCR?

Answer 8

V, J and C

Question 9

How many different genes make up the heavy chain of the TCR?

Answer 9

V, D, J and C

Question 10

True or False: Interaction of peptide-MHC with TCR is sufficient to activate a naive T cell

Answer 10

False - 2 signals are required

TCR -> Peptide-MHC interaction only provides signal 1.

Signal 2 comes from co-stimulation by T cell CD28 and APC CD86 interaction.

Question 11

What two events cause upregulation of co-stimulatory molecules like APC CD86 and T cell CD28?

Answer 11

Infection and Inflammation.

Question 12

MHC class I presents peptide to what cell?

Answer 12

CD8+ T cell

Question 13

MHC class II presents peptide to what cell?

Answer 13

CD4+ T cell

Question 14

Describe the killing mechanisms of CD8+ cytotoxic T cells.

Answer 14

1. CD8+ FasL binds to the infected cell’s Fas receptor, which activates caspases and the apoptotic cascade.
2. Release of TNF-alpha that binds to receptors on the infected cell to initiate apoptosis
3. Release of Perforins which allow granzymes to invade the infect cell and induce apoptosis.

Question 15

How are Th1 cells produced?

Answer 15

Exposure of naive T cells to IL-12

Question 16

How are Th2 cells produced and under what circumstances are they present in high levels?

Answer 16

Exposure of naive T cells to IL-4

In allergy and asthma

Question 17

How are Th17 cells produced?

Answer 17

Exposure of naive T cells to TGF-ß and IL-2

Question 18

How are Treg cells produced and what key process are they involved in?

Answer 18

Exposure of naive T cells to TGF-ß and IL-10

Crucial in Immune Tolerance

Question 19

How do Th1 cells help other immune cells?

Answer 19

Release of IL-2 and IFN-gamma to stimulate CD8+ T cells to proliferate, differentiate and become activated.

Release of IFN-gamma also activates Macrophages

Question 20

How do Th2 cells help B cells?

Answer 20

Produce cytokines: IL-2, IL-4, IL-5 and IL-13

These cytokines stimulate class switching to IgG, affinity maturation, antibody production, proliferation and differentiation.

Question 21

How do Th17 cells fight extracellular pathogens?

Answer 21

Release of IL-17 and Il-22 cytokines, which stimulate Epithelial cells and Fibroblasts to produce anti-microbial peptides, improe wound healing and upregulate chemotaxis to recruit neutrophils.

Question 22

What is the function of Treg cells?

Answer 22

Production of anti-inflammatory cytokines - TGF-ß,IL-10 and through cell-cell contact, suppress activation of APCs, antibody and cytokine production, as well as control of the function of NK and CD8+ T cells.