QUESTIONS AND ANSWERS
What ligand determines whether bone marrow stem cells will differentiated in B
cells or T cells?
Notch, Notch positive cells become T cells while Notch negative cells become B
cells
How does negative selection ensure T cells don't respond inappropriately to
peptide-MHC complexes not found in the thymus?
AIRE is a protein that induces expression of proteins not found in the thymus, ex.
lung protein, to ensure that T cells do not react to proteins found throughout the
body after undergoing negative selection
Bone marrow stem cells exposed to Notch will become
T cells
Where are Notch ligands found?
The thymic epithelium
Which process is responsible for driving CD4 or CD8 expression?
,Positive selection
Describe positive selection
MHC is presented to naive T cells. T cells which bind well to MHC are positively
selected for. If there is weak binding, the cell undergoes apoptosis (programmed
cell death). If the cell binds strongly to MHCII, the cell upregulates ThPOK and
downregulates Runx3 to become a CD4+ T cell. Otherwise, the cell becomes a
CD8+ T cell
ThPOK+Runx3-
CD4+ T cell
ThPOK-Runx3+
CD8+ T cell
Describe negative selection
If a T cell binds too strongly to MHC, the cell undergoes apoptosis
Why is negative selection important?
,It is a measure to protect against autoimmunity
How do T cells move through the thymus?
1. Arrive to thymus via corticomedullary junction
2. Differentiate into T cells in thymic epithelium
3. Move into thymic cortex where they proliferate and express TCR
4. Selection process
5. Move to thymic medulla
6. Leave via corticomedullary junction
What is the role of Bcl-2?
Prevents apoptosis by inhibiting Bax and Bak
What is the function of Bax and Bak?
Open mitochondrial membrane, releasing cytochrome C, triggering apoptosis
What is the function of Fas?
Induces apoptosis
, How does the signal from an antigen influence T cell survival?
Antigen signal prevents apoptosis by upregulating Bcl-2, without a signal from
antigen, T cells downregulate Bcl-2, leading to apoptosis as a protection measure
against autoimmunity
Where do lymphocytes reach maturity?
Primary organs
ex. bone marrow, thymus
Where do mature lymphocytes interact with antigen?
Secondary organs
ex. lymph nodes, spleen, tonsils
What does the cortex of the thymus contain?
immature T-lymphocytes