L10 - Activation and differentiation of T cells II

Question 1

Why do we need different subtypes?

Answer 1

Different pathogens need different immune responses to eliminate them

These different immune responses rely on a battery of cytokines to drive them - a major source being released by CD4+ T ‘helper’ (Th) cells

Need different types of CD4+ Th cells to deal with the different types of pathogens

Question 2

Cytokines: what are they, do they have long or short-range effects, and what do they do?

Answer 2

“small proteins released by cells that have specific effects on interactions between cells, on communications between cells or on the behaviour of cells”

May have systemic effects but mostly acts within short distances

Different cytokine ‘messages’ promote the differentiation and function of CD4+ T-cells

Question 3

CD4+ T-cell subsets: how many are there, what are they, and what do they do?

Answer 3

Three (four?) - TH1cells, Th2 cells, effector Th cells (Th17, TFH), and special regulatory Th cells (Treg)

Th1 - essential in responses to intracellular pathogens (e.g. viruses, some bacteria)

Th2 - essential in responses to extracellular pathogens (e.g. helminth parasitic worms)

Th17 - fungal/bacterial response at epithelial surfaces

TFH - aid B follicles in lymph nodes and helps them make antibodies

Treg - suppress potentially self-harmful T-cells can arise in the periphery

Question 4

Th1 cells: what cytokines do they produce?

Answer 4

• Interleukin 2 (IL-2)
• Interferon – gamma (IFN-γ)
• Lymphotoxin (LT)

Question 5

Th2 cells: what cytokines do they produce?

Answer 5

• IL-4
• IL-5
• IL-9
• IL-13

Question 6

What are the differences between Th1 and Th2 actions?

Answer 6

Th1 - act to instantly destroy infected cells to prevent pathogen spread

Th2 - act to control the infection and repair the surrounding tissue

Question 7

How are different Th cells formed?

Answer 7

Signal 1 - antigen recognition by CD4+ T-cell receptor (presented by MHCII)

Signal 2 - co-stimulatory molecule interaction (CD28-CD80/86), interaction strengthened by adhesion receptors (ie LFA1-ICAM1 interaction) leading to clonal expansion (via IL-2)

SIGNAL 3 - cytokine signalling to T-cells to allow T-cell differentiation

Question 8

Signal 3 for Th1 and Th2 cells

Answer 8

Th1:
* IL-12 (e.g. from dendritic cell)
* IFN-leccy (e.g. from Th1 cell)

Th2:
* Number of cytokines from epithelial cells (e.g. TSLP)
* IL-4
* Other Th2 cells
* Initially from basophil?
* Innate lymphoid cells?

leccy

Question 9

Th1/2 subset regulation: how does it occur and what does this allow for?

Answer 9

Th1 and Th2 subsets cross-regulate each other:
* Th1 cells downregulate the production of Th2 cells by the secretion of IFN-γ
* Th2 cells downregulate the production of Th1 cells by the secretion of IL-4

• Responses can often become “polarised” towards Th1 or Th2-dominated responses (helps immune response ‘specialise’ to a specific pathogen)

Question 10

Benefits and weaknesses of Th cells

Answer 10

Th1:
* Benefit - good at responding to intracellular pathogens
* Weakness - may cause autoimmunity, may cause rejection

Th2:
* Benefit - good at responding to extracellular pathogens
* Weakness - may cause allergy, may cause autoimmunity

Th17:
* Benefit - fungal/bacterial defence at epithelial surfaces
* Weaknesses: may cause autoimmunity

Question 11

Th17: what is it, what does it do, what cytokines are it produced by, and what cytokines does it produce?

Answer 11

Effector T-helper cell

Thought to be involved in immune regulation at epithelial surfaces (lungs intestines, etc)

The following cytokines must all act upon a Naive T-cell to form a Th17 cell:
* TGF-beta leccy
* IL-6
* IL-1

• IL-17
• IL-21
• IL-22

Question 12

TFH: what are they, what do they do, and how do they do it?

Answer 12

T-follicular helper cell

T cells that are specialised to go to the B cell follicles (germinal centres) of lymph nodes to help B cells make antibodies

They acquire a special receptor on their surface to move there

Question 13

Thymus T-cell selection: how are correct T-cell receptors formed?

Answer 13

If a T-cell receptor binds self-antigen too strongly, T-cells die

If the T-cell receptor is non-functional, T cells die

If the T-cell is functional but doesn’t bind to self-antigen too strongly, T-cells survive

Question 14

Treg: what are they, what do they do, what effects do they express, where are they produced, and what cytokines cause their production?

Answer 14

Regulatory T-cells

Suppress potentially self-harmful T-cells that may arise in the periphery

Inhibit harmful T-cells in many different ways (still not completely understood):
* Anti-inflammatory cytokines
* Outcompete effector
* T-cells for resources
* Kill self-reactive T-cells

Natural/thymic Tregs - made in the thymus as part of normal T-cell development

Induced/peripheral Tregs - in peripheral tissues/organs, produced by IL-2, TGF-beta(?)

• TGF
• IL-10

Foxp3 ???? google or leccy

Question 15

How do we know that Tregs have significance in autoimmune regulation?

Answer 15

Mice - lack of Tregs causes autoimmune disease

Question 16

Is T-cell differentiation permanent?

Answer 16

Mostly, but T-cell plasticity does exist

Question 17

What triggers signal 1 in CD4+ T-cell activation:
*

Answer 17

T-cell recogniisng co-stimulatory molecle on dendritic cell

Question 18

Which cytokine/s are primarily involved in the differentiation of Th17 cells?

• IFN-gamma and IL-12
• IL-4
• TGF-beta, IL-1 and IL-6
• IL-17

Answer 18

TGF-beta, IL-1 and IL-6

Question 19

Which of these is a classical co-stimulatory signal for CD4+ T cell activation?

• LFA-1 on T cell binding to ICAM-1 on dendritic cell
• CD28 on T cell binding to CD80 or CD86 on dendritic cell
• Antigen presented by MHC-II on dendritic cell binding to T cell receptor on T cell
• MHC-II on dendritic cell binding to CD4 on T cell

Question 20

What is believed to be an important function of the immunological synapse?

• Promotes initial contacts between a T cell and a dendritic cell
• Causes up-regulation of co-stimulatory molecules on a dendritic cell
• Clusters molecules in specific locations to promote T-cell activation
• Promotes deletion of self-reactive T cells

Answer 20

Clusters molecules in specific locations to promote T-cell activation

Answer 21

Because we need different T cell responses depending on our age

Because we need different T-cells for different climates

Because we need different t-cells to fight different pathogens

Question 22

Which type of T helper cell primarily drives allergy?

• Th1 cell
• Th2 cell
• Th17 cell
• T follicular helper cell

Answer 22

Th2 cell

Question 23

What is the major function of clonal expansion?

• To promote prolonged interactions between T cells and dendritic cells
• To enhance the number of antigen-specific CD4+ T cells
• To increase the number of dendritic cells to present antigen
• To promote enhanced effector function of CD4+ T cells

Answer 23

To enhance the number of antigen-specific CD4+ T cells