T Cell Development and Self Tolerance

Question 1

What is the immune system tolerant to?

Answer 1

• Self
• Harmless antigens (e.g. food and environment)
• Commensal bacteria

Question 2

What about the repertoire of T cells and B cells means that some may be self-reactive?

Answer 2

The repertoire is very large, so some end up being self-reactive.

Question 3

What, and where, do T cells originate from and where do they mature?

Answer 3

They are lymphoid progenitors in the bone marrow.

Migrate to the thymus where they then mature.

Question 4

What do sufferers of DiGeorge’s syndrome suffer a lack of?

Answer 4

Mature T cells

Question 5

Which chromosome is mutated in DiGeorge’s syndrome?

Answer 5

Chromosome 22

Question 6

Where does V(D)J recombination occur for T cells and B cells?

Answer 6

B cells in Bone marrow

T cells in Thymus

Question 7

How does the size of the thymus vary from before brith to adulthood?

Answer 7

Before birth, the thymus is fully developed.

During puberty, it then increases in size.

With age, it then atrophies and fat replaces thymocytes that originally existed.

Question 8

By what age is degeneration of the thymus usually completed?

Answer 8

30

Question 9

Are T cells that harm self positively selected or negatively selected?

Answer 9

Negatively selected

Question 10

Where do T cell receptor genes undergo gene rearrangement?

Answer 10

Thymus

Question 11

What is thymic stroma made up of and what is the site of?

Answer 11

Consists of epithelial cells and connective tissue.

Site of T cell development and selection.

Question 12

What are the two parts of the thymus?

Answer 12

Cortex and Medulla

Question 13

What happens to thymocytes during positive selection and negative selection?

Answer 13

In positive selection, if the thymocyte has a TcR that is able to recognise antigens from self-MHC it is kept.

In negative selection, if the thymocyte recognises self-antigens from self-MHC it is removed.

Question 14

What happens to thymocytes have TcR that are able to recognise self-MHC expressed on cortical epithelial cells?

Answer 14

They are induced to survive, differentiate and mature

Question 15

What happens to thymocytes have TcR that are NOT able to recognise self-MHC expressed on cortical epithelial cells?

Answer 15

They die via apoptosis

Question 16

What cells are found at the cortico-medullary junction of the thymus?

Answer 16

Dendritic cells and macrophages

Question 17

What happens to T cells that modestly bind to MHC I & II on macrophages and dendritic cells at the corticomedullary junction?

Answer 17

They pass through to the medulla

Question 18

Where does positive selection and negative selection occur and what cells are involved?

Answer 18

Positive selection occurs in the cortex and is done by cortical epithelial cells

Negative selection occurs in the medulla and is carried out by dendritic cells

Question 19

What is the only type of cell to not express MHC I and why is this the case?

Answer 19

Red Blood Cells

Because they don’t have a nucleus

Question 20

What does AIRE stand for and what is it?

Answer 20

Autoimmune Regulator

A transcription factor that is expressed at high levels by thymic medullary epithelial cells. Its role is to eliminate self-reactive T cells

Question 21

What could a mutation in the AIRE gene lead to?

Answer 21

Autoimmune polyendocrine system (APS-1)

Question 22

What is anergy?

Answer 22

Absence of a normal immune response to a particular antigen or allergen.

Question 23

What happens in ignorance during peripheral tolerance?

Answer 23

Self-reactive lymphocytes fail to recognise or respond to some self-antigens of the periphery. Therefore, they don’t die and don’t become anergic.

Question 24

What are immunologically privileged sites?

Answer 24

Sites where antigens are anatomically sequestered (e.g. eyes, testis and placenta)

Question 25

What could happen if antigens from anatomically sequestered sites were released?

Answer 25

Autoimmunity

Question 26

What is sympathetic ophthalmia?

Answer 26

When physical trauma to one of the eyes leads to autoimmunity to both eyes, which can cause blindness.

Question 27

What is induction of anergy?

Answer 27

When the binding of antigen makes a lymphocyte unresponsive

Question 28

What is clonal exhaustion?

Answer 28

When the consistent activation of T cells by a specific antigen leads to the activated T cells becoming worn out and eventually dying by apoptosis

Question 29

What could a deficiency in Tregs lead to?

Answer 29

An autoimmune disorder

Question 30

What is oral immunotherapy?

Answer 30

Introduction of a small amount of an allergen to induce antigen specific tolerance.

Continuous administration can promote tolerance (hoped to be used for peanut allergies).