Practical 1: The Thymus Flashcards
List the two primary lymphoid organs
Thymus
Bone marrow
Describe the location of the thymus
Anterior mediastinum
Resting on the heart
Describe the anatomical structure of the thymus
(4)
Bi-lobed
Protected by adipose tissue
Held in place by a ‘stalk’
Good blood supply - blood vessels in and out
List the parts of a thymic lobe
(4)
Capsule
Cortex
Medulla
Septum
Describe the histological structure of the thymus
(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
When does involution begin?
Soon after birth but really progresses after puberty in adolescence
Define a primary lymphoid organ
Primary lymphoid organs are responsible for the maturation of an immune cell population
What cell do T cells develop from?
T cell progenitor - produced in bone marrow then travels to thymus in circulation
What happens to T cells after they have matured?
They leave the thymus and move to the secondary lymphoid tissues
Define a secondary lymphoid organ
Secondary lymphoid organs increase the chances matured immune cells have at meeting an antigen
What is another name for septae?
Trabecula
What are mitotic bodies?
Cells undergoing mitosis
What type of cells are found in the cortex?
Mitotic bodies are found, especially neat the edge
Mitotic bodies are found in the thymus, what does this indicate?
Proliferation occurs in the thymus
What is the cortical-medullary junction?
This is where the cortex and medulla meet
What is found at the cortical-medullary junction?
Specialised vessels called post capillary vessels are found here
Briefly describe the movement of a progenitor T cell into the thymus
(5)
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
What is meant by T cell maturation?
T cells get their T cell receptor
What does the T cell receptor consist of?
Two chains of proteins
What are the two types of T cell receptors?
alpha-beta
gamma-delta
What are the thymus cells called?
Thymocytes
What CD molecules are naive T cells positive for?
They are double positive, positive for both CD4 and CD8
What happens to a T cell after it gains it’s receptor?
(5)
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
Describe positive selection of T cells
(5)
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
What happens if a T cell reacts with MHC Class I?
T cell will keep it’s CD8 and lose its CD4
T cell will become a cytotoxic T cell
What happens if a T cell reacts with MHC Class II?
T cell will keep it’s CD4 and lose its CD8
T cell will become a helper T cell
Where does positive selection take place?
Cortex
Where does negative selection take place?
Medulla
Describe negative selection
(2)
T cell moves to medulla where mTECs test T cells for self receptors
Any thymocytes with a high-affinity for self are killed
What are mTECs?
(3)
Medullary thymic epithelial cells
They are bone-marrow derived APC e.g. macrophages or DENDRITIC CELLS
They are responsible for negative cells
What are AIREs?
(3)
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
What cells are responsible for positive selection?
CTECs
What cells are responsible for negative selection?
MTECs
What percentage of thymocytes become T cells?
2 %
What do APECED stand for?
Autoimmune
Polyendocrine
Candidiasis
Ectodermal
Dystrophy
What is APECED?
(3)
Two mutated AIRE genes, not functioning properly
Therefore T cells are never negatively selected properly
Results in autoimmunity where the cells attack multiple organs
Where is AIRE located?
Chromosome 21
What is meant by the ‘starry sky’ in the thymus?
Apoptosis of thymic cells by macrophages
What is thymic involution?
Thymus is invaded by adipose tissue
Loss of significant thymic tissue to adipose tissue
What does thymic involution look like?
Only ‘islands’ of thymic tissue remain
What are Hassall’s corpuscles?
mTECs that no longer express AIRE but instead produce whirls - mTECs are old
How do you identify a Hassall’s Corpuscle?
Found more so in the medulla than cortex
Have no lumen
Red colour
No erythrocytes
What is produced by Hassall’s Corpuscles?
Thymic stromal lymphopoietin
Give one function of TSLP
Activation of thymic dendritic cells
What increases involution?
Acute involution caused by stress, cancer, disease, pregnancy and lactation
Why were different strains of mice used in the Miller Paper?
(2)
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
What were the conclusions of the Miller Paper?
(2)
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
