Immuno Tolerance

Question 1

How are non thymic self-antigen reactions cells eliminated?

Answer 1

AIRE-TF that is mainly expressed in the medulla of the thymus

• induces expression of genes expressed by other organs
• negative selection of thymocytes reactive to these antigens

Question 2

What is the disease associated with failure of central tolerance gene AIRE?

Answer 2

Autoimmune polyendocrine syndrome (APS)

-endocrine organs are destructed by antibodies and lymphocytes

Question 3

What is dominant suppression?

Answer 3

imposed by professional regulators

-Regulatory T cells stop the other guys

Question 4

What is cell intrinisic inactivation?

Answer 4

Change of the state of the T cells-become unresponsive to stimulation
=anergy

Question 5

What diseases is tolerance prevent?

Answer 5

autoimmune disorders such as IBD(inflammation of the colon) or hyperimmune disorders (allergy)

Question 6

What type of T cells do FoxP3- come from?

Answer 6

CD4

Question 7

What are myeloid derived suppressor cells?

Answer 7

become potent immunological regulators when exposed to inflammation (IFN gamma) and blocks T cell responses
-often tumor associated

Question 8

What is clonal anergy?

Answer 8

When T cells are stimulated in a manner that is incomplete- cells become non-response to further stimulation

Question 9

What do mature nTregs express?

Answer 9

CD25, Il2R alpha chain

Question 10

What happens when there is a mutation in the FoxP3 gene?

Answer 10

IPEX

-multiple tissue damages caused by self reactive T cells

Question 11

What are nTregs against vs. iTregs?

Answer 11

nTregs:Self-antigens(make sure the tcells dont attack self)
iTregs: foreign antigens (make sure the Tcells dont attack things that should be there like babies)

Question 12

Most cells that are reactive against self antigens are going to die (central tolerance)but there are regulatory cells that can stop the immune response against self antigens, where is the generation of these T cells?

Answer 12

hassal corpuscles

Question 13

What is TSLP?

Answer 13

In the hassall’s corpuscles and helps differentiation of FOXP3_ regulatory T cells via activation of a subset of dendritic cells

Question 14

What are iTregs induced by?

Answer 14

antigen presenting cells that are present in the mucosal environment such as the intestine

Question 15

What cofators needed to induce iTregs?

Answer 15

A/D

Question 16

Tr1 cells produce what?

Answer 16

Il 10-potnet immuno-suppressive cytokine

Question 17

Are Tr1 cells foxp3 negative ?

Answer 17

yes

Question 18

What do Tr1 cells develop in response to?

Answer 18

antigenic stimulation when TGF beta and IL27 are present

-vitamin D upregulates IL10 -linked to generation of Tr1 cells

Question 19

What do Tregs develop in response to?

Answer 19

TGF beta and IL2

Question 20

Is direct cell-cell essential for Tregs?

Answer 20

Yes
CTLA-4 plays a significant role

• they do use soluble factors such as TGF beta and IL10 but that only to enhance where as Tr1 mainly uses IL10
• adenosine is another effector molecule generated by Tregs to suppress other lymphocytes

Question 21

When is anergy induced?

Answer 21

When antigen is presented in absence of costimulatory signal CD28 (binds to B7-which is only expressed on APCs)

Question 22

Does CTLA have a higher affinity for B7?

Answer 22

yes

Question 23

What does CTLA do?

Answer 23

competes with CD28 for B7

-and recruits signaling molecules that suppress TCR signaling and blocks antigen activation

Question 24

Can CTL4 be used to improve the frequency of graft vs host disease?

Answer 24

yes, there is a man made CTLA-4IG, which is soluble and can block autoimmune disorders

Question 25

What are myeloid derived suppressor cells?

Answer 25

become potent immunological regulators when exposed to inflammation (IFN gamma) and blocks T cell responses
-often tumor associated
-use NO and depletion of nutrients to stop cell growth
-INF gamma is reaching soem level and they block everything in the area.
want to get rid of this when theres tumors but want it for autoimmmunity