(Section B: Immunology) Lecture 15: T-Cell Immunity II

Question 1

Describe:

Route taken by developing T Cells

Answer 1

1. Start at Corticomedullary Junction
2. Goes into cortex
3. Goes into medulla
4. Finishes at Corticomedullary

Question 2

What happens during T Cell development in the Thymus?

Answer 2

1. TCR genes are recombined to generate T cells with diverse repertoire of TCRs
2. T cells w/ TCRs that can recognize MHC molecules are positively selected
3. T cells w/ TCRs that recognize MHC + peptide with high affinity are negatively selected

Question 3

What is the outcome of T Cell Development in Thymus?

Answer 3

T cells are generated with TCRs ready to be activated by MHC molecules associated with nonself peptides

Question 4

What are the gene loci of TCR?

Answer 4

1. Alpha
2. Beta
3. Delta
4. Gamma

Question 5

What is the order of rearrangement for TCR genes?

Answer 5

1. TCR beta rearranges first
2. TCR alpha rearranges second

Question 6

What is needed to form pre-T receptor?

Answer 6

Pre-T alpha and other proteins pairing together

Question 7

The proteins together form what kind of complex?

Answer 7

CD3 complex

Question 8

What are the phases in T-Cell development?

Answer 8

1. Double Negative
2. Double Positive
3. Single Positive

Question 9

What explains the variable region amino acid diversity?

Answer 9

T-cell receptor alpha and beta gene rearrangement

Question 10

What are the 4 main steps of T cell development?

Answer 10

1. TCR Beta chain rearrangement
2. Beta selection
3. TCR Alpha chain rearrangement
4. Positive selection

Question 11

TCR Beta chain rearrangement

Answer 11

If successful (chance of it not being successful):
* Forms Pre-TCR
* Signals for Beta selection

Question 12

Beta Selection

Answer 12

• Stops additional TCR beta chain rearrangement
• Stimulates proliferation
• Stimulates expression of CD4 and CD8 coreceptors
• TCR alpha chain rearrangement

Question 13

What also happens during beta selection?

Answer 13

Pre-TCR signalling

Question 14

TCR alpha chain rearrangement

Answer 14

Results in:
* Mature TCR Immature signaling
* Negative selection for high affinity due to costimulation

Question 15

Positive selection

Answer 15

• Selects for intermediate affinity costimulation
• Selection is by MHC-I or MHC II

Question 16

What happens in mature TCR?

Answer 16

Mature TCR Mature Signalling
* Proliferation
* Effector function (CD4+/CD8+)

Question 17

How are CD4+/CD8+ cells selected in the Cortex?

Answer 17

• 90-96% have no interaction, results in death by neglect
• 2-5% have high affinity interaction, results in negative selection
• 2-5% have low/intermediate affinity interaction, results in positive selection

Question 18

What cells are responsible for selection in cortex?

Answer 18

cTEC
* Cortex Thymic Epithelial Cells

Question 19

How are CD4+/CD8+ cells selected in the medulla?

Answer 19

• Cells are negatively selected
• Surviving ones have already differentiated into CD4+/CD8+ cells when crossing to the medulla

Question 20

What cells participate in selection in the medulla?

Answer 20

mTEC
* Medulla Thymic Epithelial Cells

Macrophages (Dendritic cells etc.)

Question 21

What is special about mTEC cells?

Answer 21

Contains AIRE (turns certain genes on, self antigens)

Question 22

T Cell Tolerance Induction

Answer 22

• 90-96% Low affinity for self - Death by neglect
• 2-5% Intermediate affinity for self - Survive
• Less than 1% High affinity for self - Turn to T regulatory cells
• 2-5% Very high affinity for self - Deleted

Question 23

What are T Cells activated by in the Lymph Nodes?

Answer 23

Dendritic Cells in the T Cell Zones of the lymph node

Question 24

What happens why T Cells are activated?

Answer 24

Differentiate into effector cells and leave the lymph node to travel to infected tissue

Question 25

How many signals do TCRs need for activation? What are they?

Answer 25

3
1. TCR binding to antigen/MHC
2. Costimulatory receptors
3. Cytokines

Question 26

True or False:

T Cells only need 2 out of 3 signals for activation

Answer 26

False, all three must be present for full activation

Question 27

How can dendritic cells activate both CD4 and CD8 T Cells?

Answer 27

By Cross Presentation of Antigen on MHC I and MHC II

Question 28

How does T Cell Tolerance Induction work?

Answer 28

Anergy
* Lack of costimulatory receptor (non-APC cell) fails to activate T-cell
* Anergic T-cell continues through circulation without activity

Question 29

What happens to the T Cell in T Cell Activation?

Answer 29

• Induces metabolic changes (prepares the T cell for cell division and differentiation into effector cells)
• Activates genes
• Differentiate into effectors (Th and Tc cells)

Question 30

What is the purpose of cytotoxic T Cells (CD8+)?

Answer 30

Effectors that kill virus-infected cells

Question 31

Describe:

Killing Mechanism of CD8+ cells

Answer 31

1. CTL approaches Target Cell
2. Initial contact
3. Granules congregate to CTL/Target Cell contact
4. More granules, target cell death begins

Question 32

What is the killing mechanism of CD8+ cells?

Answer 32

• Using perforin to punch holes in the membrane
• Releasing Granzyme B to cause apoptosis

Question 33

What is essential in the clearing of virus infections?

Answer 33

1. IFN-alpha and IFN-beta are produced first after viral infection
2. Cytokine release, a wave of NK cells follows
3. Virus eliminated when virus-specific T cells finish killing virus infected cells

Question 34

True or False:

Most CD8+ effector cells have long lives

Answer 34

False, most effector CD8+ cells have short half-lives

Question 35

What happens to the surviving pathogen-specific T-cells?

Answer 35

Memory Cells
* 35% of circulating T Cells in a healthy young adult
* 60% in individuals over 70 years old

Question 36

How does HIV work?

Answer 36

Infects CD4+ T cells and kills them
* Results in severe immunodeficiency (AIDS), infection, and potentially death