Restraining the Immune System + Intestinal Immune System

Question 1

CD4+ T cells that produce cytokines that attenuate or restrain the immune response

Answer 1

inducible regulatory T cells

Question 2

Cytokines produced by iTregs

Answer 2

• TGFbeta reduces T cell proliferation and the killing rate of CTLs
• IL-10 blocks activation of T cells through co-stimulatory signals by plugging into CD28 and also reduces proliferation

Question 3

CTLA-4

Answer 3

• B7 binds to this to repress activation of T cells
• mobilized to surface of activated T cells in increasing amts
• several thousand times more affinity than the activating receptor (CD28)

Question 4

Checkpoint proteins

Answer 4

CTLA-4 and PD-1

- designed to decommission cells as the battle winds down

Question 5

PD-1/PD-1L

Answer 5

PD-1L on cells under attack bind to PD-1 on experienced T cells to decrease proliferation of T cells

Question 6

T cells can live a long time, so how do we get rid of them?

Answer 6

• activation-induced cell death (AICD)
• repeatedly stimulated T cells get fatigued and get ‘rewired’ so they become sensitive to the binding of their Fas surface proteins to another T cell’s FasL receptor and => apoptosis of both T cells

Question 7

commensal bacteria get through the one cell layer thick barrier all the time… what gives?

Answer 7

not in constant state of inflammation bc:

• special macs monitor the perimeter of gut epithelium and don’t secret inflammatory cytokines if they phagocytose the odd commensal
• IgA neutralizes invaders and can transcytose them back into the gut lumen; but IgA does NOT bind to Fc receptors on professional phagocytes or activate complement

Question 8

What happens to B cells and T cells when activated by a commensal in the lamina propria?

Answer 8

• don’t return to spot where the organism entered
• B and T cells are instead distributed throughout the length of the lamina propria to be on guard generally for commensals that occasionally breach the epithelial barrier in the intestines
• these cells ‘on site’ provide a quick response that minimizes inflammation

Question 9

Dendritic cells activated in lamina propria …

Answer 9

don’t travel farther than the mesenteric lymph nodes

Question 10

B cells and T cells activated in the lamina propria…

Answer 10

stay there

Question 11

Anti-inflammatory environment of intestines

Answer 11

normal gut = epithelial cells produce TGFbeta and IL-10 ti help T cells become iTregs and keep things calm
- DCs important in determining whether TGFbeta causes a Th cell to become a Th17 or an iTreg = IL-6 production is key (If no IL-6 TGFbeta seems to stimulate T cell to become iTreg and produce more TGFbeta)

Question 12

What happens when a pathogen or large numbers of commensal bacteria breech the gt epithelium?

Answer 12

• Th1 cells can be activated, likely by DCs that respond to unique PAMPs on pathogens or other signals (DAMPs) when a lot of tissue is destroyed by infection
• Th17 cells arise when DCs provide IL-6 in addition to TGFbeta