The Structure and Function of the Thymus Flashcards

1
Q

Where are T cells produced?

Where do they mature?

A
  • They are produced in the bone marrow.

- They mature in the thymus.

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2
Q

List the chains that form T cell receptors.

Which are analogous to heavy chains and which are analogous to light chains?

A

1 - TCR alpha chain (analogous to light).

2 - TCR beta chain (analogous to heavy).

3 - TCR gamma chain (analogous to heavy).

4 - TCR delta chain (analogous to light).

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3
Q

List the possible combinations of TCR receptor chains.

A

1 - Alpha + beta chains.

2 - Gamma + delta chains.

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4
Q

List the genes that encode the T cell receptor chains.

Which of these genes is not used for ‘light’ chains?

A

Lymphocyte antigen receptor genes:

1 - Variable (V).

2 - Diversity (D).

3 - Joining (J).

4 - Constant (C).

  • The diversity gene is not used for ‘light’ chains.
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5
Q

Which process ensures that every lymphocyte expresses a different antigen receptor?

A

Random recombination of lymphocyte antigen receptor gene segments.

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6
Q

If diversity of lymphocyte antigen receptors is generated at random, how are autoreactive antigen receptors avoided?

A
  • By negatively selecting against self antigen receptors and positively selecting for non-self receptors.
  • By negatively selecting against receptors that don’t recognise any antigen.
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7
Q

Give an example of a functional difference between T cell receptors and B cell receptors.

A

T cell receptors can only recognise antigen presented by MHC, whereas B cell receptors can recognise antigen without MHC.

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8
Q

Describe the organisation of cells in the thymus.

A
  • The cortex contains cortical epithelium.
  • Blood vessels and dendritic cells straddle the boundary between the cortex and medulla.
  • The medulla contains medullary epithelium.
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9
Q

Describe the process of selection of T cells in the thymus.

A

1 - T cells begin in the cortex, where they are negatively selected against if they don’t bind to MHC at all.

2 - Surviving T cells continue to the medulla, where the are negatively selected against if they bind to MHC too strongly because these T cells are likely to be self-reactive.

3 - In the medulla, T cells that bind to MHC class 1 commit to the CD8 lineage, whereas T cells that bind to MHC class 2 commit to the CD4 lineage.

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10
Q

List the types of T cell tolerance.

A

1 - Central tolerance.

2 - Peripheral tolerance.

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11
Q

Where does central T cell tolerance occur?

A

In the thymus.

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12
Q

List the sources of peripheral T cell tolerance.

A

1 - Ignorance.

2 - Anergy.

3 - Cell death.

4 - Regulatory T cells.

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13
Q

How do T cell precursors mature into T regulatory cells in the thymus?

A
  • Positive / negative selection of T cells for maturation is determined by the strength of the T cell receptor signal (the binding strength to MHC).
  • There is an area between positive selection (moderate binding strength) and negative selection (excessively strong binding strength) where T cells are selected for T regulatory cell maturation.
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14
Q

What is the function of T regulatory cells?

A

To suppress autoreactive lymphocytes that have escaped negative selection.

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15
Q

List 3 proteins expressed by T regulatory cells.

A

1 - CD4.

2 - CD25.

3 - FOXP3.

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16
Q

List 3 mechanisms by which T regulatory cells suppress autoreactive lymphocytes (and therefore contribute to peripheral tolerance).

A

1 - Cytokine mediated: release of IL-10 and TGF beta.

2 - Competition for IL-2.

3 - Contact-dependent.

17
Q

What is the autoimmune regulator (AIRE)?

What is its function?

A
  • A transcription factor expressed by medullary thymic epithelial cells.
  • It regulates promiscuous gene expression so that tolerance to proteins expressed in peripheral tissues can also occur in the thymus.
  • E.g. AIRE directs insulin expression in the thymus so that T cells developing there that recognise insulin as non-self and undergo negative selection (protects against diabetes).
18
Q

What is IPEX?

A

An autoimmune disorder caused by a deficiency of FOXP3, which impairs T regulatory cell development.

19
Q

What is APECED?

A

An autoimmune disorder caused by a deficiency of AIRE.

20
Q

List 2 genetic causes of thymus aplasia.

A

1 - FOXN1 deficiency.

2 - DiGeorge syndrome.

21
Q

Give an example of a non-genetic risk factor for thymus aplasia.

Why is this less dangerous than genetic causes of thymus aplasia?

A
  • Age.
  • Thymus atrophy due to age is not dangerous because T cells are long-lived, whereas other causes of thymus atrophy are dangerous because the atrophy occurs before the T cells develop.
22
Q

Give an example of a factor that improves the likelihood of success of bone marrow transplantation.

A

Good thymus function.

23
Q

Give an example of a treatment of DiGeorge syndrome.

A

Thymus transplantation.

24
Q

How is a thymus transplantation done?

A

By transplanting strips of donor thymus into the quadriceps femoris muscle.