Lecture 12 9/22/23

Question 1

What is immune tolerance?

Answer 1

body’s ability to recognize and tolerate its own cells/molecules while mounting immune responses against foreign/harmful substances

Question 2

What does a breakdown in self tolerance result in?

Answer 2

autoimmune disease

Question 3

What are the characteristics of central tolerance?

Answer 3

-established during immune cell development in primary lymphoid organs
-immature immune cells undergo selection process to eliminate cells that recognize self-antigens

Question 4

What are the characteristics of peripheral tolerance?

Answer 4

-occurs in secondary lymphoid organs and peripheral tissues
-achieved through regulatory T cells

Question 5

What is the overarching goal of Tregs?

Answer 5

regulate and suppress immune responses to self-antigens that escape central tolerance

Question 6

What are the general properties of Tregs?

Answer 6

-generated by exposure to TGF-beta
-produce IL-10 and TGF-beta
-involved in immune suppression and maintenance of mucosal homeostasis

Question 7

What receptors/proteins are present on the surface of Tregs?

Answer 7

-CD3
-CD4
-CD25
-CD39
-CD73
-PRRs
-CTLA-4
-LAG-3
-TCR

Question 8

What cells are inhibited by Tregs?

Answer 8

-CD4 T cells
-CD8 T cells
-NK cells
-APCs

Question 9

What are the mechanisms of Treg-mediated suppression?

Answer 9

-cell surface molecules
-immunosuppressive cytokines
-IL-2 consumption
-cytolysis

Question 10

What is the function of CTLA-4 and LAG-3?

Answer 10

to suppress APC function and inflammatory cytokines

Question 11

What is triggered by the binding of CTLA-4 to CD80 or CD86?

Answer 11

production of IDO by DCs, which suppressed Teff cell activity

Question 12

What is the result of high expression of CD25 and high affinity of cytokine receptors?

Answer 12

-inhibition of Teff cell proliferation
-inhibition of IL-2 synthesis

Question 13

What immunosuppressive cytokines are produced by Tregs?

Answer 13

-TGF-beta
-IL-10

Question 14

How do TGF-beta and IL-10 function?

Answer 14

-prevent 1st order cytokines from activating their associated T helper cells
-promote naïve T cells to produce more Tregs

Question 15

What is the result of high expression levels of CD39 and CD73 on Tregs?

Answer 15

production of adenosine

Question 16

How does adenosine impact the immune system?

Answer 16

-inhibits NK cells, APCs, and active T cells
-increased number of Tregs
-increases immunosuppressive activity of Tregs

Question 17

How do the immunosuppressive cytokines function in tissue repair?

Answer 17

they promote tissue repair and stimulate M2 macrophages

Question 18

Which granules allow Tregs to kill unwanted immune cells?

Answer 18

-perforin
-granzymes

Question 19

Which bacteria are able to activate DCs?

Answer 19

-Bacillus fragilis
-Clostridia

Question 20

How do B. fragilis and Clostridia activate DCs?

Answer 20

by stimulating TGF-beta and retinoic acid production

Question 21

What do TGF-beta and retinoic acid do?

Answer 21

promote Treg activation

Question 22

Why is it important that Lactobacillus dominate the vaginal microbiome during reproductive age?

Answer 22

-Lactobacillus break down glycogen and produce lactic acid
-lactic acid causes acidic pH
-acidic pH inhibits growth of other bacteria and fungi and suppresses inflammatory reactions