"Microbiology/Immunology T Cell Development" MARY Flashcards
The _____ is the major site of T-cell development.
Thymus
When we say that T-cells become lineage committed in the thymus, what does this mean?
CD4 and CD8
T/F: Each of us has a unique, self-restricted TCR repertoire.
True.
T-cells are tolerized to what in the thymus during T-cell development?
Self antigen
Explain the concept of MHC restriction.
A few things:
- HLA is another way of saying MHC
- MHC I is recognized by all nucleated cells.
- MHC II are only on APCs.
- The TCR must recognize both the antigen (peptide) AND the MHC complex
T/F: CD4 and CD8 lineage T-cells recognize different MHC molecules.
True. CD8 binds to the alpha-3 domain of MHC I. CD4 binds to the beta-2 domain of MHC II.
T/F: TCR development involves gene rearrangements.
True
DiGeorge syndrome involves what deficiency?
Human T-cell immunodeficiency
What is a “nude” mouse”
Lacks hair AND thymic epithelial cell differentiation bc of loss of transcription factor. Can use to study T-cell immunodeficiency.
What forms the thymus in embryonic/fetal development?
3rd pair of pharyngeal puch (endoderm) and cleft (ectoderm). 1st hematopoietic precursors are planted in the thymus at 8 weeks gestation. Thymus produces chemotactic factors that attract T-cell precursors.
B-cells are born in the bone marrow and grow in the thymus. Presuming they make it out of the thymus, what are their next destinations?
Secondary lymphoid tissue, ie GI tract, spleen, lymph nodes.
T-cell precursors are also known as:
Prothymocytes
How do prothymocytes enter and leave the thymus?
Enter through the corticomedullary junction, exit through the medulla venules. **Migration is influenced by chemokines and sphingosine 1-phosphate receptors
How does flow cytometry use “single cell” technique?
A graph plots each cell as a dot, and the clusters represent common populations of cells, for example the graph on page 321. Know how to read these!!
T-cells early in development are:
(a) double negative
(b) double positive
(c) single positive
(a) double negative, using cell surface markers to identify stage
CD2 receptor, found in double negative early T-cells, is for what function?
Cell signaling and adhesion
Give the steps in lineage commitment, starting with the CD2 + “double negative” (-CD4/-CD8) cells.
- Cell becomes gamma-delta and leaves thymus (function unknown) OR becomes alpha-beta, the typical T-cell.
- If becoming an alpha-beta cell, cell undergoes beta, gamma delta rearrangements and becomes double positive (+CD4/+CD8) - pre-TCR assembly -
2b. Cell tests beta chain (first checkpoint). - Cell can “short circuit” and still become gamma-delta cell, or can undergo alpha, gamma, delta rearrangements.
- If successful, alpha part is done and cell is a committed alpha-beta cell.
What is the main reason why most genetic rearrangements in T-cell development fail?
Reading frame issues
How does a pre-TCR “test” its beta chain?
Goes to the surface with a helper molecule because it will not go alone (heterodimer –> superdimer –> pre-T-cell receptor)
How many attempts can be made to achieve a productive rearrangement of the beta chain locus? How this different from alpha chain building?
Two beta chain attempts. Alpha has more chances because it can try further and further upstream regions, and has 3 or more chances to produce a functional alpha chain.
During the alpha chain rearrangements in T-cell receptor development, what region is not used?
D region. Once this chain is removed, the piece must become an alpha chain.
During what stages of TCR development can RAG-1 and RAG-2 be identified?
During the rearrangements of beta and alpha chains.
When does a developing T-cell become double positive?
At the end of successful beta and alpha chain creation.
In what section of the thymus do progenitor cells proliferate?
Medulla
*Cells go back into medulla once they are SP committed to test their MHC interactions before leaving the thymus.
