Lymphocyte Development Flashcards
What do TCRs bind to?
- Antigen-derived peptide
- peptide bound to MHC class
Describe the structure of the TCR.
- regions
- disulfide bonds
- transmembrane domain
- recombination chains
α chain = VJ
β = VDJ
How do T-cells express unique antigen receptors?
VDJ/VJ recombination
Cells entering the thymus are (_____) to becoming a lymphocyte and express antigen-specific receptors.
A. not committed
B. naive/mature
C. B cells
A. not committed
T/F. Cells leaving the thymus are naive/mature T-cells and express specific antigen TCRs.
True
T-cells development occurs in the:
thymus
Describe the migration of T-cell development.
- precursor T-cells develop in the bone marrow
- Immature T-cells migrate from bone marrow through the blood into the thymus
- Immature T-cells travel through the thymus at the cortex
- T-cells that undergo selection migrate to the medulla
List the stages the T-cells undergo in the thymus.
- Double negative (DN): do not express CD4 or CD8
- Double positive (DP): express both CD4 and CD8
- Single positive: expresses either CD4 or CD8
In which stage does the recombination of the TCR gene segments (VDJ/VJ) occur?
DN stages
What are the two stages T-cell development occurs?
- Early thymocyte development
- commit to T-cell lineage
- Initiate V(D)J recombiation
- expand cells - T cell maturation
- positive selection
- negative selection
- lineage commitment
When thymocytes arrive at the thymus, what early cells do they have the possibility of becoming?
- NK cells
- dendritic cells
- B cells
T/F. When cells arrive at the thymus they are T-cells.
False. When cells arrive at the thymus they aren’t technically T-cells.
T cell lineage commitment occurs due to signals received by the progenitor cell from thymic epithelial cells. Name that signaling receptor.
Notch
If the cell has Notch+ or Notch- which cell lineage are they committed to?
Notch+: T cells
Notch-: B cells
When thymocytes progress to the DN stages what essentially occurs?
- gets TCR α and β
- cells will test β chain via β selection = proliferation
- initiates α chain rearrangement and selection
- VDJ rearrangement is stopped once selection occurs
- enters DP stage
After β selection, what stage do the thymocytes enter?
DP
What occurs in the DP stage?
- functional TCR
- cell expresses both CD4 AND CD8 (CD4+, CD8+)
- undergoes positive and negative selection
Describe positive and negative selection of thymic cells.
- positive selection: selects thymocytes receptors capable of binding self-MHC molecules with low affinity
- MHC restriction - negative selection: selects against thymocytes receptors with high affinity for self-MHC/peptide complexes
- self tolerance
MHCI is present on …
all nucleated cells
- T cells
- B cells
- macrophages
- dendritic cells
- epithelial cells of the thymus
MHCII is present in …..
APCs
- B cells
- macrophages
- dendritic cells
- epithelial cells of the thymus
The function of cortical thymic epithelial cells (cTEC)?
express high levels of MHC class I and II
- mediate positive selection
Double positive thymocytes learn (____) in the thymus.
MHC restriction
What are the 3 possible outcomes when T cells encounter self-peptide/MHC?
- TCRs can’t bind = death by neglect
- TCRs bind too strongly (high affinity) = apoptosis
- TCRs bind just right (low affinity) = positive selection
- recognizes and interacts with self peptide
- ensures MHC restriction
- becomes CD4 or CD8, single positive
Negative selection ensures….
self tolerance (central tolerance)
If a thymocyte has a high affinity for binding antiself what occurs?
Clonal deletion via apoptosis
What are AIRE proteins? Are they in relation to positive or negative selection?
Negative selection
- induces expression of mTECs
- binds epigenetic marks to recruit transcription factors
- mediate negative selection
What cells help regulate self tolerance and what do they express?
Treg cells (CD4+)
Express: FoxP3 transcription factor
How do Treg cells negatively regulate?
- deplete stimulating cytokines
- produce inhibitory cytokines (IL-10)
- inhibit APC activity
- directly kill T cells (cytotoxic T cells)
What peripheral mechanisms protect against autoreactive thymocytes?
- some self-anitgens are hidden
- some self-antigens are presented by non-APCs
On the BCR complex, what is involved in signal transduction?
- Igα and Igβ transduce signals via ITAMs
Where do B-cells develop?
begins in the bone marrow and completed in the periphery
Describe positive and negative selection in B-cells.
Positive: signaling through BCR
Negative: eliminated auto-reactive B-cells
Immature B-cells express which ligand on their membrane?
A. IgM
B. B220
C. CD25
D. CD19
E. All of the above
E. All of the above
What are the two possible outcomes of BCRs being tested against self-anitgens?
- Clonal deletion: autoreactive cells eliminated by apoptosis
- Receptor editing: reactivation of light-chain recombination
Once in the spleen for maturation, what do B-cells do?
- express IgM and IgD
- recirculate between blood and lymphoid organs
- respond to antigens with T-helper cells by producing antibodies
