Lecture 13

Question 1

Where does negative selection occur? And what is negative selection?

Answer 1

Medulla
-Eliminate T cells w/ TCRs binding to self antigen w/ high affinity

Question 2

How do you induce negative selection against tissue specific self proteins?

Answer 2

mTECs (medullary thymic epithelial cells)

Question 3

What is AIRE?

Answer 3

A transcription factor that supports expression of tissue specific proteins in mTECs

Question 4

What is AIRE deficiency?

Answer 4

Multi-organ autoimmune disease
-APECED (autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy)

Question 5

What are regulatory T cells?

Answer 5

A type of CD4 T cell that suppresses other T cells by directly secreting chemokines or suppress dendritic cells

Question 6

What is Foxp3?

Answer 6

A transcription factor that confers the suppressor program Treg (CD4) cells

Question 7

What 2 ways does AIRE control self tolerance?

Answer 7

1. Negative Selection
2. Generation of regulatory T cells

Question 8

What happens if the T cell does not bind w/ high enough affinity to trigger negative selection?

Answer 8

AIRE will differentiate into a Treg cell

Question 9

What is HEV?

Answer 9

High endothelial venules
-allows circulating T cells to enter a lymph node to sample foregin antigens presented by APCs

Question 10

How do lymphocytes know where to exit?

Answer 10

Homing

Question 11

What 3 families of molecules direct cellular movement?

Answer 11

1. Selectins (rolling)
2. Chemokines (activation)
3. Integrins (arrest & diapedesis)

Question 12

What is Rolling (Selectins)

Answer 12

Slows down lymphocyte to allow for future interaction
-Interaction between L-selectin on T cells that allow for future interaction

Question 13

What is Activation (Chemokines)

Answer 13

T cell & chemokine interacts to activate LFA-1
-Interaction between CCR7 expressed on T cells which leads to LFA-1

Question 14

What is Arrest and Diapedesis (Integrins)

Answer 14

Cell can exit go to tissue
-LFA-1 binds to ICAM-1 and ICAM-2 so that cells can leave the blood and enter the lymph node

Question 15

How do T cells and dendritic cells establish interaction?

Answer 15

1. LFA-1 and ICAM interaction T cells are able to initiate contact w/ DC (regardless of TCR specificity)
2. Binding of matched TCR and peptide/MHC complexes activate LFA-1 to induce T cell-DC interaction

Question 16

In addition to TCR stimulation, what do naive T cells require

Answer 16

They need a 2nd signal (co-stimulatory signal) otherwise they become anergic

Question 17

Anergy

Answer 17

T cells become inactive and die

Question 18

What does CD28 do?

Answer 18

Co-stimulatory molecule (B7) binds to CD28 on naive T cell

Question 19

What does B7 do?

Answer 19

Co-stimulatory molecule that is expressed at high levels when dendritic cells have been activated by innate receptors coming into contact w/ PAMP

Question 20

How many signals are required for priming naive T cells?

Answer 20

2

Question 21

What happens when naive T cell has co-stimulatory and specific signal?

Answer 21

Activates T cell

Question 22

What happens when naive T cell has only Specific signal

Answer 22

T cell becomes anergic

Question 23

What happens when there is only co-stimulatory signal?

Answer 23

No effect on T cell

Question 24

How many signals does an effector T cell need?

Answer 24

Only 1 signal

Question 25

What is DC maturation

Answer 25

Mature DC upregulates B7–>B7 2nd signal

Question 26

What are 3 mechanisms for preventing autoimmune reactions in the T cell population?

Answer 26

1. Negative selection in the thymus (mTECs, mDCs, deletes T-cells w/ high affinity to self antigens)
2. Production of regulatory T cells (suppresses effector T cells–> escape (-) selection still has high–> Fox affinity to self
3. Induction of anergy in the absence of innate immune signals–>Needs co-stimulatory signal

Question 27

What is VLA-4 and VCAM-1

Answer 27

activates endothelium