Thymus Flashcards
Primary lymphoid organs
Where lymphocytes are formed and mature
Into B and T cells
Bone marrow and thymus
Secondary lymphoid organs
Maintain mature naive lymphocytes and initiate an adaptive immune response Sites of lymphocyte activation by antigens
4 parts of thymus structure
Septum
Capsule
Cortex
Medulla
Hassall’s corpuscle
In the medulla
Don’t know exactly what they are or what they do
Dying epithelial cells
Cellular composition of thymus (5 cell types)
Thymocytes (immature T cells) Cortical epithelial DCs Macrophages Epithelio-reticular cells
Nurse cells
Provide nutrients and factors for thymocytes to divide
Thymocytes
Immature T cell precursors
Migrate to thymus from bone marrow
In the thymus thymocytes rearrange T cell receptor genes
They are then selected based on TCR specificity either to mature into T cells or die by apoptosis
3 steps to become and immunocompetent T cell
- Successfully rearrange a T cell receptor gene
- Positive selection (weak recognition of self MHC and peptide) by interacting with cortical epithelial cells
- Negative selection (strong recognition of self peptide) by interacting with DCs
Positive versus negative selection
Positive: doesn’t recognize self MHC or peptide, will die
Negative: recognizes self too strongly, will die
Pre-TCR (and what 3 things happen when it functional)
Made of the functional TCR beta chain, and a pre alpha chain
If its functional, then 3 things happen:
1. Stops TCRbeta chain locus rearrangement (allelic exclusion)
2. Activates TCR alpha chain rearrangement
3. Stimulates proliferation
Double negative thymocytes
Non-productive TCR rearrangement leads to cell death by apoptosis
Productive TCR rearrangement leads to cell survival and proliferation
Surviving cells up-regulation expression of CD4 and CD8 and become double positive thymocytes
Double positive thymocytes
Positive selection: weak binding to self MHC/peptide complex on cortical epithelial cells leads to survival, no binding leads to apoptosis Have both CD4 and CD8 Interact with either class 1 or class 2 molecules expressed by cortical epitheliar cells Surviving cells downregulate expression of either CD4 or CD8 and become single positives
Single positive thymocytes
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
Cortical epithelial cells
Interact with double positive thymocytes in the cortex to mediate positive selection
Dendritic cells
Located in the thymic medulla
Interact with single positive thymocytes and mediate negative selection
Don’t want to delete thymocytes that detect foreign antigen
Macrophages
Phagocytosis of apoptotic thymocytes
Epithelio-reticular cells
Form a continuous cellular layer that lines the capsule and around the blood vessels
This is called the blood-thymus barrier (regulates what can get in and out
Blood thymus barrier
Formed of epithelio-reticular cells that form a continuous cellular layer that lines the capsule and around the blood vessels
Prevents exposure of the immature thymocytes to blood borne antigens
Hassall’s corpuscules
Epithelial cells eventually undergo degeneration and organize themselves into concentric esoinophilic whorls of material, called thymic corpuscles (Hassall)
Unknown function
Appear very early in life
Nothing more than debris, nonfunctional degenerative remains
Is thymic differentiation based on pos/neg selection model sufficient to explain self tolerant state?
No
Tregs might be important
Thymic involution
Normal process
As we age, the functional parenchyma of the organ is replaced with fat and connective tissue, and the organ as a whole diminishes in size
Thymus isnt completely nonfunctional though
