Exam 5: Chapter 7 Flashcards
Why are the GD cells produced during embryogenesis lacking in diversity?
Each cell within a wave uses the same Vg segment and same D rearrangement
What is positive selection?
The selection of TCRs that bind self MHC isoforms
Do T cells with two functional TCRs ever make it into the periphery?
No
What region of the body does the second wave of embryonic GD cells colonize?
The reproductive tract epithelium
What cells populate the cortex?
Cortical epithelial cells
How do thymocytes transition from being Double Positive to being Single Positive?
CD8 is initially shut off, and the T cell tests to see if the TCR signal is still present. If it is, the cell is a CD4+ cell. If the signal is not present, CD4 is shut off and IL7 sends a signal to turn CD8 back on. The cell then becomes a CD8+ cell
How does T cell development proceed through the thymus?
T cell development starts in the cortex and proceeds into the medulla; naïve T cells that survive selection exit from the medulla
How do B cells and T cells differ in terms of longevity?
B cells last a few days or weeks, while T cells last years
What are Regulatory T cells (Treg)?
CD4+ cells that are also CD25+ and express transcription factor FoxP3; these cells regulate T cell response to prevent them from destroying self tissues
What is the medulla?
The inner portion of the thymus
How are lymphoid progenitor cells marked for T cell lineage?
Via notch signaling
What happens to cells that fail to productively rearrange their TCR?
They die via apoptosis and are removed by the macrophages in the cortex
What are the four checkpoints in T cell development?
Productive Beta chain arrangement, Productive Alpha chain arrangement, Positive Selection, Negative Selection
Which T cells are initially made during embryogenesis?
GD cells
What do T cells do if they survive both positive and negative selection?
They migrate through the blood stream and to the secondary lymphoid organs, where they collect in the T cell areas and interact with specific antigens
What is negative selection?
The deletion of TCRs that bind self peptides
What phenotype is observed in those lacking a thymus?
A SCID-like phenotype
What are immature T cell progenitors called?
Thymocytes
What cells populate the medulla?
Medullary epithelial cells, macrophages, dendritic cells
What percentage of double positive thymocytes are positively selected?
2%
When does the thymus begin to shrink in size?
Around puberty
Why are productive rearranged AB cells referred to as Double Positive T cells?
Pre-T cell receptor signaling induces the expression of both CD4 and CD8 on the cell surface
What is the cortex?
The outer portion of the thymus
How many tries does the beta chain have to produce a productive rearrangement?
4 tries - 2 per locus
How does positive selection work?
Cortical epithelial cells express both class 1 and class 2 MHC, which present self peptides; double positive cells that are able to interact with the MHC are positively selected for
What is the first step of T cell development?
Progenitor cells migrate from the bone marrow to the thymus
What is required for the suppression of auto-reactive T cells?
For both the auto-reactive T cell and the Treg cell to interact with the same antigen-presenting cell
What happens if auto-reactive T cells escape negative selection?
The T cells enter a state of anergy that “pauses” them for a period of time
Where do T cells develop?
In the thymus
Which cells mediate negative selection?
Bone marrow-derived macrophages and dendritic cells
What region of the body does the first wave of embryonic GD cells colonize?
The skin epithelium
Why is there a possibility that two functional T-cell receptors are produced by a single cell?
Both alpha chain loci rearrange at the same time, and both can have productive rearrangements
What are the two possibilites that occur after Alpha/Gamma/Delta rearrangement?
- Gamma and Delta genes rearrange productively and produce a GD T cell
- Alpha gene rearranges productively and produces an AB T cell
What happens if FoxP3 is mutated in Treg cells?
No Treg cells are produced and an X-linked autoimmune disease occurs as a result
How are all possible peptides able to be expressed by the thymus?
The transcription factor AIRE (autoimmune regulator) ensures that nearly every gene is expressed in the thymus, thus allowing most self peptides to be presented
Where does negative selection occur?
In the medulla of the thymus
Which T cell gene(s) rearrange first?
Gamma, delta, and beta genes
Where does positive selection occur?
In the cortex of the thymus
Which T cell chain has more chances to rearrange?
The alpha chain
How does negative selection work?
The thymic epithelium presents class 1 and class 2 peptides. T cells that bind moderately (i.e. to MHC but not peptide) survive, while cells that bind tightly (i.e. to both MHC and peptide) die
What are the two possibilities that occur after Beta/Gamma/Delta rearrangement?
- Gamma and Delta genes rearrange productively and produce a GD T cell
- Beta gene rearranges productively and pairs with pTalpha to form the pre-T cell receptor
What induces progenitors to proliferate into thymocytes?
Interaction with cortical epithelial cells
What happens if there is a lack of notch signaling?
T cell development will be blocked
What would happen if a transplant patient received a bone marrow transplant with completely different HLA types than their own?
The derived T-cells would be positively selected on the recipient’s HLA allotypes, but the antigen-presenting cells in other bodily tissues would present antigens on donor HLA types; no T cells would thus be able to bind HLA and respond to the infection
Where are the precursor cells to T cells “born?”
In the bone marrow
What happens if AIRE is mutated?
Patients end up with autoimmune polyglandular syndrome type 1
How does the Pre-TCR produce a signal?
By crosslinking to form a superdimer
What is the role of the pre-T cell receptor?
To turn off recombination of the beta, gamma, and delta genes
Why are early thymocytes called Double Negative thymocytes?
They express neither CD4 nor CD8
