Thymus Flashcards
Where is the thymus located?
In the anterior mediastinum (between the lungs and below the thyroid)
What is the general structure of the thymus?
multiple lobules, each with a cortex and medulla that are surrounded by a capsule
What 5 cell types make up the thymus?
- thymocytes (immature T cells)
- Cortical epithelial cells
- Dendritic cells
- Macrophages
- Epithelio-reticular cells
Which two factors mediate the homing of immature T cell precursors to the thymus from the bone marrow
- alpha 4 integrin
2. CD44
Which occurs first? positive or negative selection? what does this involve?
Positive selection (weak recognition of self MHC and peptide) by interacting with cortical epithelial cells
What is the order of rearrangement of the TCR chains?
the TCRß chain is rearranged first and then, only if this is successful, the TCR alpha chain can be rearranged
What happens at the pre-TCR expression stage?
- Stops TCRb chain locus rearrangement (alleleic exclusion)
* Activates TCRa chain rearrangement •Stimulates proliferation
What is the order of gene rearrangement in the TCR alpha and beta chains?
D–>J, then V –> DJ for the ß chain
just V –> J for the alpha chain
- doesn’t have a D region
What two things are stimulated with the a/ß TCR is expressed?
- proliferation
2. CD4 and CD8 expression
What do immature thymocytes become after successful rearrangement of their TCR genes? where?
double positive thymocytes
in the cortex
What do CD4+/CD8+ thymocytes undergo?
Positive selection
What are the two possible outcomes of positive selection?
- Weak binding to self MHC/peptide complex on cortical epithelial cells leads to survival.
- No binding leads to apoptosis.
What happens to CD4+/CD8+ thymocytes that survive positive selection?
downregulate expression of either CD4 or CD8 (depending on TCR specificity) and become single positive thymocytes
What is being tested for during negative selection?
Strong binding to self MHC/peptide complex on Dendritic cells.
What are the two possible outcomes from negative selection?
- Strong binding to self MHC/peptide complex on DC leads to apoptosis.
- Weak or no binding leads to survival and T cell maturation
What is the role of cortical epithelial cells in thymocyte maturation? where are they?
Interact with double positive thymocytes in the cortex to mediate positive selection.
What is the role of dendritic cells in thymocyte maturation?
- Dendritic cells are located in the thymic medulla.
* They interact with single positive thymocytes and mediate negative selection
What is the role of macrophages in thymocyte maturation?
• Phagocytosis of apoptotic thymocytes
What is the role of epithelio-reticular cells in thymocyte development? what do they form? what does this prevent?
- Form a continuous cellular layer that lines the capsule and around the blood vessels.
- This is called the blood-thymus barrier.
- This barrier prevents exposure of the immature Thymocytes to blood borne antigens.
What are Hassall’s corpuscles?
Epithelial cells that have degenerated and formed concentric eosinophilic whorls of material in the medulla of the thymus
Is thymic differentiation based on pos/neg selection model sufficient to explain self tolerant state?
not really no
what explains the self tolerant state (in addition to positive and negative selection?
the presence of Treg cells
How are Treg cells generated? what is their avidity like?
on the autoreactive side but are still positively selected and induced to become Treg cells
What is thymic involution?
a normal process by which the functional parenchyma of the organ is replaced with fat and connective tissue, and the organ as a whole diminishes in size
