Practical 1: The Thymus

Question 1

List the two primary lymphoid organs

Answer 1

Thymus

Bone marrow

Question 2

Describe the location of the thymus

Answer 2

Anterior mediastinum
Resting on the heart

Question 3

Describe the anatomical structure of the thymus
(4)

Answer 3

Bi-lobed
Protected by adipose tissue
Held in place by a ‘stalk’
Good blood supply - blood vessels in and out

Question 4

List the parts of a thymic lobe
(4)

Answer 4

Capsule
Cortex
Medulla
Septum

Question 5

Describe the histological structure of the thymus
(5)

Answer 5

Surrounded by a connective tissue capsule which forms extensions called septae in the tissue

Septae divide the thymic tissue into lobes and lobules

The outer darker staining region is the cortex (more cells = more nuclei here to stain darker)

The inner lighter staining region is the medulla

Blood vessels can be seen in the septae

Question 6

When does involution begin?

Answer 6

Soon after birth but really progresses after puberty in adolescence

Question 7

Define a primary lymphoid organ

Answer 7

Primary lymphoid organs are responsible for the maturation of an immune cell population

Question 8

What cell do T cells develop from?

Answer 8

T cell progenitor - produced in bone marrow then travels to thymus in circulation

Question 9

What happens to T cells after they have matured?

Answer 9

They leave the thymus and move to the secondary lymphoid tissues

Question 10

Define a secondary lymphoid organ

Answer 10

Secondary lymphoid organs increase the chances matured immune cells have at meeting an antigen

Question 11

What is another name for septae?

Answer 11

Trabecula

Question 12

What are mitotic bodies?

Answer 12

Cells undergoing mitosis

Question 13

What type of cells are found in the cortex?

Answer 13

Mitotic bodies are found, especially neat the edge

Question 14

Mitotic bodies are found in the thymus, what does this indicate?

Answer 14

Proliferation occurs in the thymus

Question 15

What is the cortical-medullary junction?

Answer 15

This is where the cortex and medulla meet

Question 16

What is found at the cortical-medullary junction?

Answer 16

Specialised vessels called post capillary vessels are found here

Question 17

Briefly describe the movement of a progenitor T cell into the thymus
(5)

Answer 17

Progenitor T cell leaves bone marrow

Cell travels to thymus via circulation

Cell enters thymus at cortical-medullary junction

Cell travels to outer region of cortex in nearest lobule via post capillary vessels

Double positive naive T cells mature here and gain a receptor

Question 18

What is meant by T cell maturation?

Answer 18

T cells get their T cell receptor

Question 19

What does the T cell receptor consist of?

Answer 19

Two chains of proteins

Question 20

What are the two types of T cell receptors?

Answer 20

alpha-beta

gamma-delta

Question 21

What are the thymus cells called?

Answer 21

Thymocytes

Question 22

What CD molecules are naive T cells positive for?

Answer 22

They are double positive, positive for both CD4 and CD8

Question 23

What happens to a T cell after it gains it’s receptor?
(5)

Answer 23

It begins to move back towards the cortical-medullary junction

As it moves it must undergo positive selection in the cortex

After reacting with a MHC (Class I or II) it moves to the medulla

Here, any cells that react to self are killed

Very few cells make it to the junction but they leave here and move to secondary lymphoid organs

Question 24

Describe positive selection of T cells
(5)

Answer 24

T cells with a receptor must meet a MHC molecule in the cortex

The receptor must react with either MHC Class I or MHC Class II

T cell keeps CD8 and loses CD4 (-helper) if reacts with MHC Class I (all nucleated cells)

T cell keeps CD4 and loses CD8 (-cytotoxic) if it reacts with MHC Class II (APCs)

T cell will only get the signal to survive if it reacts with MHC

Question 25

What happens if a T cell reacts with MHC Class I?

Answer 25

T cell will keep it's CD8 and lose its CD4 T cell will become a cytotoxic T cell

Question 26

What happens if a T cell reacts with MHC Class II?

Answer 26

T cell will keep it's CD4 and lose its CD8 T cell will become a helper T cell

Question 27

Where does positive selection take place?

Answer 27

Cortex

Question 28

Where does negative selection take place?

Answer 28

Medulla

Question 29

Describe negative selection (2)

Answer 29

T cell moves to medulla where mTECs test T cells for self receptors Any thymocytes with a high-affinity for self are killed

Question 30

What are mTECs? (3)

Answer 30

Medullary thymic epithelial cells They are bone-marrow derived APC e.g. macrophages or DENDRITIC CELLS They are responsible for negative cells

Question 31

What are AIREs? (3)

Answer 31

Autoimmune regulatory epithelial cells A subtype of mTECS - mTECs with better antigen presentation Have peripheral tissue antigens for self which can be shown to T cells before they leave the thymus

Question 32

What cells are responsible for positive selection?

Answer 32

CTECs

Question 33

What cells are responsible for negative selection?

Answer 33

MTECs

Question 34

What percentage of thymocytes become T cells?

Answer 34

2 %

Question 35

What do APECED stand for?

Answer 35

Autoimmune Polyendocrine Candidiasis Ectodermal Dystrophy

Question 36

What is APECED? (3)

Answer 36

Two mutated AIRE genes, not functioning properly Therefore T cells are never negatively selected properly Results in autoimmunity where the cells attack multiple organs

Question 37

Where is AIRE located?

Answer 37

Chromosome 21

Question 38

What is meant by the 'starry sky' in the thymus?

Answer 38

Apoptosis of thymic cells by macrophages

Question 39

What is thymic involution?

Answer 39

Thymus is invaded by adipose tissue Loss of significant thymic tissue to adipose tissue

Question 40

What does thymic involution look like?

Answer 40

Only 'islands' of thymic tissue remain

Question 41

What are Hassall's corpuscles?

Answer 41

mTECs that no longer express AIRE but instead produce whirls - mTECs are old

Question 42

How do you identify a Hassall's Corpuscle?

Answer 42

Found more so in the medulla than cortex Have no lumen Red colour No erythrocytes

Question 43

What is produced by Hassall's Corpuscles?

Answer 43

Thymic stromal lymphopoietin

Question 44

Give one function of TSLP

Answer 44

Activation of thymic dendritic cells

Question 45

What increases involution?

Answer 45

Acute involution caused by stress, cancer, disease, pregnancy and lactation

Question 46

Why were different strains of mice used in the Miller Paper? (2)

Answer 46

A strain A mouse would accept a graft from strain A mouse because the MHC molecules would be the same But a strain A mouse would not accept a graft from strain B mouse if mouse A has a functioning T cell population because the different MHC molecules should be recognised as antigen

Question 47

What were the conclusions of the Miller Paper? (2)

Answer 47

When thymus removed at birth a strain B mouse accepted a skin graft from a strain A mouse Therefore there was no T cell population as the skin graft would have been rejected otherwise