(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
Hassall’s corpuscles
- what happens here?
- Destruction of Self-reactive cells (its in the medulla)
2. Treg formation that converts some Self-reactive CD4+ T cells to Treg cells that actually Prevent autoimmune disease
Draw analogy between parts that get somatically recombined in TCRs and Antibodies?
- Alpha chain of TCRs is similar to that of the light chain of antibodies
- Beta chain of TCRs is like the heavy chain of antibodies
Chromosomes of alpha and beta chains?
14 and 6 respectively
What happens to the alpha chain if beta chain rearrangement isn’t successful?
- nothing because it was never made
Why are you super fucked if you lose both RAG-1 and RAG-2 enzymes?
RAG is involve in BOTH B cell and T cell somatic rearrangement
- without these your lymphocytes would float around bald
Why is losing Terminal Deoxynucleotidyl Transferase (TdT) No Big Deal
You will have slightly less variance in your heavy chain and beta chains but it probably won’t be clinically significant
Suppose you have T cell tumor. How could you find out what phase of the process is messed up?
- Look at surface proteins
- You can do this because tumor cells generally express the same surface proteins as whatever cell that they came from
