Lecture 8- Cellular Cooperation

Question 1

When CD4+ T cell differentiates into a subset T cell class (e.g. TH1 or TH2), can it switch again?

Answer 1

No, the differentiation is terminal.

Question 2

What cytokines do TH1 cells synthesize? What is activated by these cytokines?

Answer 2

IFN-gamma and IL-2. CD8+ T cells, NK cells, and macrophages are activated (these are the effectors of cell-mediated immunity).

Question 3

What cytokines do TH2 cells synthesize? What does each cytokine activate?

Answer 3

IL-4 (most important to remember), IL-13, and IL-5.

IL-4 and IL-13 activate plasma cells to make IgE and IgG4.

IL-5 activates eosinophils.

Question 4

What is T cell cross inhibition?

Answer 4

The cytokines made by either TH1 or TH2 CD4+ T cells will inhibit the development of its counterpart (example: IL-4 made by TH2 cells inhibit TH1 cells from forming and vice versa).

Question 5

What types of pathogens stimulate the development of TH1 cells?

Answer 5

Viruses

Question 6

What types of pathogens stimulate the development of TH2 cells?

Answer 6

Helminth worms, allergens.

Question 7

Which effector cells are activated by IFN-gamma?

Answer 7

Effectors of cell mediated immunity: CD8+ T cells, NK cells, and macrophages.

Question 8

What effector functions does IL-4 lead to?

Answer 8

Proliferation of plasma cells that synthesize either IgE or IgG4

Question 9

What pathogens activate TH17 T cells, what cytokine does it produce, and what is the clinical significance of this?

Answer 9

Fungi and extracellular bacteria activate TH17 cells. They make IL-17, which activates inflammatory responses at mucosal surfaces, especially. Likely involved in auto-immunity conditions like RA, MS, and psoriasis.

Question 10

Which cytokine, made by APCs, stimulates TH1 development?

Answer 10

IL-12

Question 11

Are T helper cells required for B cell class switching in the germinal centers?

Answer 11

Yes.

Question 12

What are the two requirements for T-helper and B cell cooperation in the germinal centers?

Answer 12

1) The two cells must recognize the same antigen

2) The two cells must recognize parts of a single antigen that are physically linked

Question 13

What does “mutual activation” refer to?

Answer 13

The activation of both T helper cells and B cells in the germinal centers at the same time.

Question 14

Describe the steps involved in mutual activation.

Answer 14

1) Both T helper and B cells bind the antigen, resulting in T cell stimulatory signals #1 and #2.
2) The T and B cells come together.
3) The T cell releases cytokines while at the same time the B cell puts out cytokine receptors.
4) The B cell binds the cytokines from the T cell, resulting in class switching of the B cell and Ab synthesis.

Question 15

During T Helper - B cell mutual activation, cytokines are released from the T cell that influence B cell class switching. What B cell antibodies result from T cell release of 1) IL-4 and 2) IFN-gamma?

Answer 15

IL-4 —> IgE and IgG4

IFN-gamma —> IgG3 (for compliment activation)

Question 16

Name three things that are required for CSR. What disease results if any one of these are missing?

Answer 16

1) CD40
2) CD40 ligand
3) AID (activation induced cytidine deaminase)

Hyper-IgM syndrome is when peeps can’t class switch.

Question 17

What are thymus-independent angitens? Which Ig class predominates in this immune response? Is there memory?

Answer 17

Antigens that do not require T cell help for B cells to make antibody. IgM predominates. No memory.

Question 18

Name two thymus-independent antigens.

Answer 18

1) The LPS of gram-negative bacteria

2) Capsular polysaccharides found on Strep. pneumoniae and Haemophilus influenzae b.

Question 19

Do CD8+ cells need to be activated to kill their targets?

Answer 19

Yup

Question 20

Do most viruses require CD4+ activation of CD8+ cells to kill infected host cells?

Answer 20

Yes, like HIV. Note that some do not!

Question 21

Describe the steps of the CD8+ T cell killing mechanism.

Answer 21

1. T c ell and infected cell come together.
2. MHC I and TCR bind
3. T cell releases granzymes and perforin, pore forms on infected cell.
4. Granzymes infiltrate infected cell, apoptosis is induced.
   Note: separately, FAS ligand on the T cell binds FAS on the infected sell as a backup apoptosis inducer.

Question 22

What is CTLA-4 and how does it work?

Answer 22

It is a co-stimulator with a similar structure to CD28 that also binds B7 (on APCs). CTLA-4 is expressed after an infection is cleared, and it binds B7 with a higher affinity than CD28. When CTLA-4 binds B7, inhibitory signals are sent out to end the immune response.