(07) T Cell Development Flashcards
T Cell
- Describe its distribution at different points in time
Generated - bone marrow
Maturation - Thymus
Active in - 2˚ lymphoid tissue
What are 3 differences of T cells from B cells?
- Can only recognize peptides bound to MHC
- Do not secrete Antibodies
- Have the ability to kill
What is the T-cell receptor analogous to?
Fab region of Antibodies
Distinguish between alpha-beta and gamma-delta domains
Gamma-delta
- NOT a component of the acquired immune system
- Primative - do not recognize peptide/MHC complexes (not MHC restricted)
- Mucosal epithelium of Gut primarily
- mature extrathymically
- Significant role in recognition of LIPID antigens
- Usually double negative
What is the signal transduction unit for T-cells?
- where is it found?
- Describe the components
CD3 - signal transduction unit expressed on ALL T Cells
- alpha, beta, delta, gamma, epsilon units
- zeta unit is mostly cytoplasmic
What is the functional difference between CD4 and CD8 receptors?
- what do we call cells with these?
CD4 - recognizes and binds (weakly) to MHC class II
CD8 - recognizes and binds (weakly) to MHC class I
- Cells are CD4+ or CD8+, NEVER BOTH
What are 6 different surface markers that are expressed by T Cells?
- CD 28
- Fas ligand
- Adhesion Molecules
- CTLA-4
- PD-1
- CD4 and CD8
What is CD28?
T-cell
- Recognized B7 expressed by APCs after PRRs PAMPs
What is Fas Ligand?
T-cell
Homotrimeric protein that can bind 3 Fas receptors on a target cell and trigger programmed cell death
what is an Adhesion molecule?
T-cell
Allows T-cell to interact with APC, Vascular Endothelial Cells, and Potential target cells
What is CTLA-4?
T-cell
Acts as the breaks on T-cell differentiation and proliferation in contrast to CD28
CTLA-4, analogous to CD28, that binds B7 on APC
BUT does it 20x more effectively
*This is expressed when T-cells become activated
What is PD-1?
T-cell
- Supressor of T-cell activation/proliferation that becomes active when it binds PD-L1 or PD-L2 ligands on APCs
**Important in suppressing T-cells that bind self antigens
Thymus
- organization
- cell populations within organizational layers
Cortex
- Cortical epithelial cells
- thymocytes (immature T cells)
- Macrophages
Medulla
- Dendritic Cells
- Macrophages
- Nearly mature Thymocytes
- Hassall’s corpuscle
*between = corticomedullary junction
What are macrophages in the thymus called?
- what makes them distinct functionally and morpholically?
Tingible body macrophages
- Phagocytose Self Reactive T-cell
- Have unique appearance due to ultra high levels of chormatin
Differentiate in general terms between positive and negative selection
Positive Selection
- Things that bind are encouraged to keep living
Negative Selection
- things that bind are killed
Where do thymocytes enter the thymus and what happens when they get there?
- Enter in medulla and subcapsular area
What happens:
- They undergo somatic recombination using RAG-1/2 and TdT
- gamma/delta, and beta chains compete in rearrangement
2 possible outcomes:
- if beta finishes 1st then alpha-beta peptide
- if delta/gamma finishes 1st then delta/gamma peptide
What does the beta chain do while the alpha chain is forming?
- what problems could arise here?
- Binds pTalpha which prevents beta chain degradation
- if pTalpha is under/malexpressed then SCID would result because patient has no more functional T-cells
Expression of what other surface marker(s) occurs simultaneous with TCR expression?
CD4 and CD8 resulting in cells that are CD4+ and CD8+
Describe + selection
- MHC I and MHC II are expressed on Thymic Epithelial Cells.
- Thymocytes that binds these the tightest will survive
T or F: positive selection strongly selects for self reactive cells
True, self reactive cells will in fact bind the tightest
Before proceeding to the coritcomedullary junction, what must happen to thymocytes?
- They need to adjust their CD4 and CD8 receptors to represent what they bind
- MHC I binding –> CD8 up and CD4 down
- MHC II binding –> CD4 up and CD8 down
What happens if you lack AIRE?
Severe autoimmune disease
AIRE = Autoimmune Regulator
- transcription factor that causes expression of most body proteins in the thymus
What happens to cells that bind strongly during negative selection?
Apoptosis
During positive selection a thymocyte binds really hard to MHC I or II. What should happen to this cell in the medulla?
Medulla = positive selection
- this cell should be selected and will die
