A6: Effector Mechanisms of T Cell-Mediated Immunity

Question 1

What is the key cytokine released by T helper cells to activate macrophages?

Answer 1

IFN-gamma

Question 2

What receptor on macrophages is bound by T helper cells to cause further activation?

Answer 2

CD40L on T helper cells binds to the CD40 receptor on macrophages (and on B cells)

Question 3

What costimulatory factor on macrophages activates the helper T cells?

Answer 3

B7 on macrophages acts on CD28 receptor (and of course acts through MHC class II to CD4+, which is the first signal)

Question 4

What two signals trigger Th1 differentiation? Where do these signals come from?

Answer 4

IFN-gamma and IL-12 (IL-12 from dendritic cells that respond to bacteria, IFN-gamma from NK cells and from other Th1 cells)

Question 5

What are 3 key transcription factors that cause Th1 differentiation?

Answer 5

T-bet, Stat4, and Stat1

Question 6

What is the key cytokine of Th1 cells? How is this related to what activates it?

Answer 6

IFN-gamma. Is the most potent activator of macrophages. Because Th1 differentiation is triggered by microbes ingested by phagocytes, then Th1 promote activity of those phagocytes

Question 7

What type of infection induces the Th2 subset? What two cytokines stimulate Th2 differentiation?

Answer 7

Parasitic infections that are too large to be phagocytosed induce Th2. Stimulated by IL-4 and IL-2.

Question 8

What type of reaction are Th2 cells significantly involved in?

Answer 8

Allergic reactions (type I hypersensitivity)

Question 9

What is the effect of the Th2 subset?

Answer 9

Th2 subset responds by releasing its signature cytokines IL-4, IL-5 and IL-13. IL-4 stimulates IgE antibodies which coat parasite. IL-5 activates eosinophils, and IL-13 stimulates mucus secretion and intestinal peristalsis

Question 10

How does IL-4 induce differentiation into the Th2 subset? What is the source of IL-4?

Answer 10

IL-4 is made by mast cells and acts on GATA-3 and Stat-6 transcription facotrs. Th2 subset also produces more IL-4

Question 11

What does the Th17 develop in response to? What two cytokines mediate the Th17 differentiation and what is the source of those cytokines?

Answer 11

Th17 develops in response to bacterial and fungal infections, driven by IL-6 (in combination with TGF-beta). IL-6 is released by dendritic cells and macrophages in response to fungal glycans and bacterial peptidoglycans.

Question 12

What is the key cytokine of Th17 and what does this function to do?

Answer 12

IL-17 is key cytokine and its function is to recruit neutrophils to induce a longer-lived inflammatory response, also stimulates production of antimicrobial defensins.

Question 13

Which Th subtype is most implicated in autoimmune inflammatory diseases?

Answer 13

Th17

Question 14

Which Th subtype activates classical macrophage activation? Which one activates alternative macrophage activation?

Answer 14

Th1 activates classical macrophage activation. Th2 activates alternative macrophage activation.

Question 15

What inhibits the Th1 differentiation? What inhibits Th2 differentiation?

Answer 15

Th1 differentiation is inhibited by cytokines made by Th2 cells (IL-4 and IL-10). Th2 differentiation is inhibited by cytokines made by Th1 cells (IFN-gamma)

Question 16

What two cytokines are made by T regulatory cells to cause reduction of the inflammation response?

Answer 16

IL-10 and TGF-beta

Question 17

What is the source of T regulatory cells?

Answer 17

Tregs may develop from CD4+ T cells which may have a strong affinity for self-peptide and are not eliminated by negative selection. May also also arise from T cells which interact with antigen but do not receive costimulation via CD28

Question 18

What is the key transcription factor of T regulatory cells? What happens if there is a deficiency of this transcription factor?

Answer 18

FOXP3 is the key transcription factor. Absence of which causes IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked). Is an autoimmune disease

Question 19

How does the CD40L on T helper cells interact with antigen-loaded dendritic cells?

Answer 19

CD40L binds to the CD40 receptor present on dendritic cells, activating APCs to make them more efficient at stimulating differentiation of CD8+ T cells

Question 20

How do CD8+ cells induce killing of their target (2 mechanisms)?

Answer 20

Via perforin and granzyme B in granules and by interaction of their FasL to bind to Fas receptor on the target cell.

Question 21

What is one way that mycobacteria are able to avoid killing by CTLs?

Answer 21

Via inhibiting the fusion between phagosomes and lysosomes

Question 22

How does herpes simplex virus interfere with antigen presentation?

Answer 22

Inhibiting TAP mediated transport of peptides into the ER, thus preventing the interaction of the MHC and peptide molecules on MHC class I

Question 23

How does CMV (cytomegalovirus) defend against CTL killing? What about EBV (Epstein-Barr virus)?

Answer 23

CMV removes MHC class I from the ER and EPV inhibits proteasomal activity thus preventing the breakdown of peptides for presentation on MHC class I

Question 24

How does the Pox virus avoid killing by CTLs?

Answer 24

Pox virus forces infected cells to produce soluble cytokine receptors which act as decoys and bind and neutralize IFN-gamma and other cytokines