Effector Functions of T Cells

Question 1

List the 6 effector T cell variants.

Answer 1

1 - CD4+ Th1.

2 - CD4+ Th2.

3 - CD4+ Th17.

4 - CD4+ TFH (follicular helper).

5 - CD4+ Treg (regulatory).

6 - CD8+ T.

Question 2

List 3 immune defences against infection in interstitial spaces, blood and lymph.

Repeat the areas in which these immune defences act (as stated in this question).

Answer 2

1 - Complement.

2 - Phagocytosis.

3 - Antibodies.

• Interstitial spaces, blood and lymph.

Question 3

List 2 immune defences against infection on epithelial surfaces.

Answer 3

1 - Antimicrobial peptides.

2 - Antibodies, especially IgA.

Question 4

List 2 immune defences against infective agents in the cytoplasm.

Answer 4

1 - NK cells.

2 - Cytotoxic T cells.

Question 5

Give an example of an immune defence against infective agents in vesicles.

Answer 5

T-cell and NK-cell dependent macrophage activation.

Question 6

Describe the process of T cell activation.

Answer 6

1 - Binding of the T cell receptor to a class 2 MHC on antigen presenting cells creates an activation signal.

2 - Binding of the CD28 receptor (on the T cell) to B7 proteins CD80 and CD86 (on antigen presenting cells) creates a survival signal if the affinity of co-stimulation is sufficient.

3 - Binding of various different cytokines to receptors on the T cell will produce a differentiation signal, determining the T cell type.

Question 7

What is the primary function of CD8+ T cells?

Answer 7

To kill intracellular pathogens, especially viruses by destroying the infected host cell.

Question 8

List the 2 major killing mechanisms of CD8+ T cells.

Answer 8

1 - Granules containing perforin and granzymes.

2 - Fas ligand, which binds to Fas on the target cell, triggering apoptosis.

Question 9

How does perforin contribute to CD8+ T cell function?

Answer 9

It creates pores in the cell membrane of the pathogen, leading to cell death.

Question 10

What type of enzyme are granzymes?

Answer 10

Proteases.

Question 11

List the functions of CD4+ Th1 cells.

Answer 11

1 - To activate infected macrophages that are infected with vacuole-restricted bacteria.

2 - To provide help to B cells for antibody production.

Question 12

List 4 consequences of infected macrophage activation by CD4+ Th1 cells.

Answer 12

1 - Increased macrophage MHC expression.

2 - Increased macrophage nitric oxide production.

3 - Increased macrophage phagolysosome maturation.

4 - Increased macrophage TNF alpha production.

Question 13

Which protein stimulates CD4+ Th1 cells to activate macrophages?

Which protein is released by CD4+ Th1 cells that causes macrophage activation?

Answer 13

• The CD4+T cell responds to cognate antigen.

- The CD4+T cell secretes IFN-gamma to cause macrophage activation.

Question 14

What causes granuloma formation?

Answer 14

Partial removal of live pathogens (vacuole-restricted bacteria) from infected macrophages after activation by CD4+ T cells, which causes infected macrophages to form a fused cluster surrounded by T cells.

Question 15

What determines the path of CD4+ T cell differentiation?

Give an example of selective T cell differentiation.

Answer 15

• The molecular environment of the dendritic cell - T cell interaction, which is determined by the nature of the pathogen involved.
• E.g. a naive CD4+ T cell will differentiate into a CD4+ Th1 cell if it binds to Th1-polarising factor, which is released by the dendritic cell in response to type 1 PAMPs (other molecules are also implicated).

Question 16

How are specific lineages of CD4+ T cells upregulated?

Which cells are implicated in this process?

Answer 16

• Cytokines that initiate differentiation of CD4+ T cells of a particular lineage drives downstream pathways that upregulate that particular lineage.
• The cytokines can be derived from the dendritic cell, the T cell itself, macrophages, fibroblasts and epithelial cells.

Question 17

Describe the process of CD4+ Th1 differentiation.

Answer 17

1 - Differentiation is initiated by a differentiation signal that is generated in response to Th1-polarising factor.

2 - Further differentiation requires IL-12.

3 - Differentiation is amplified by IFN-gamma in a positive feedback loop.

4 - The transcription factor T-bet is expressed to control the transcriptional programme required for CD4+ Th1 cell differentiation.

Question 18

List 2 risks of CD4+ Th1 deficiency and 2 risks of CD4+ Th1 overabundance.

Answer 18

Deficiency:

1 - Reactivation of latent infections.

2 - Inadequate control of de novo infection.

Overabundance:

1 - Autoimmunity.

2 - Inflammatory diseases.

Question 19

List 2 functions of CD4+ Th2 cells.

Answer 19

1 - To provide help to B cells for antibody production, especially by switching to IgE.

2 - Drives alternative macrophage activation.

Question 20

Which pathogens are targeted by CD4+ Th2 cells?

Answer 20

Helminth parasites.

Question 21

Describe the process of CD4+ Th2 differentiation.

Answer 21

1 - Differentiation is initiated by a differentiation signal that is generated in response to Th2-polarising factor.

2 - Further differentiation requires IL-4, which can be present in the environment and is also secreted by the CD4+ Th2 cell itself.

4 - The transcription factor GATA3 is expressed to control the transcriptional programme required for CD4+ Th2 cell differentiation.

Question 22

List 3 secretions of CD4+ Th2 cells.

Answer 22

1 - IL-4.

2 - IL-5.

3 - IL-13.

Question 23

List 2 functions of CD4+ Th17 cells.

Answer 23

1 - To enhance the neutrophil response by increasing neutrophil recruitment.

2 - To promote barrier integrity.

Question 24

Which pathogens are targeted by CD4+ Th17 cells?

Answer 24

Fungi and some bacteria.

Question 25

Describe the process of CD4+ Th17 differentiation.

Answer 25

1 - Differentiation is initiated by IL-1 beta, IL-6 and IL-21 (TGF beta).

2 - Differentiation is maintained by IL-23.

3 - The transcription factors ROR alpha and ROR gamma-t are expressed to control the transcriptional programme required for CD4+ Th17 cell differentiation.

Question 26

Which interleukin do CD4+ Th17 cells secrete?

Answer 26

IL-17.

Question 27

List 2 functions of CD4+ TFH (follicular helper) cells.

Answer 27

1 - Express the chemokine receptor CXCR5 to allow migration towards B cell areas.

2 - Co-express a wide range of Th phenotypes to allow appropriate B cell help.

Question 28

Where in the body do CD4+ TFH (follicular helper) cells act?

Answer 28

In secondary lymphoid compartments.

Question 29

Which interleukin promotes CD4+ TFH (follicular helper) cell differentiation?

Answer 29

IL-21.

Question 30

Which transcription factor is unique to CD4+ TFH (follicular helper) cells?

Answer 30

Bcl-6.

Question 31

What is the primary function of CD4+ Treg (regulatory) cells?

How do they carry out their function?

Answer 31

• To restrict other immune responses by suppressing T cell proliferation.

They do this by:

1 - Blocking the priming of effector T cells by reducing co-stimulatory molecule availability.

2 - Preventing dendritic cell maturation.

3 - Killing mature dendritic cells.

4 - Secreting IL-10, an anti-inflammatory cytokine which inhibits the activity of various immune cells.

Question 32

List the molecules that are necessary for CD4+ Treg (regulatory) differentiation.

Answer 32

1 - IL-21 (TGF beta).

2 - Retinoic acid.

Question 33

Which transcription factor is required for CD4+ Treg (regulatory) cell differentiation?

Answer 33

FoxP3.

Question 34

List the 2 major sources from which CD4+ Treg (regulatory) cells are derived.

How do cells from each of these sources differ functionally?

Answer 34

1 - Some cells derived from the thymus.

2 - Some cells derived from the periphery as part of any peripheral immune response.

• The cells derived from the thymus are able to carry out regulatory function as soon as they leave the thymus, whereas those derived from the periphery must undergo further maturation.