Lecture 10+11: T Cells Flashcards
Where do all lymphocytes development from
Hematopoietic stem cells
What is responsible from getting lymphocytes from HSC to lymphocytes
Stromal cells and cytokines
Where does T cell development occur
Thymus
Where do T cell progenitors originate
Bone marrow
What dictates movement of lymphoid progenitors to thymus
Chemokines
What cytokine is critical to development and commitment to T cell line
IL-7
What is IL-7 made by
Thymic stromal cells
Mutations in IL-7 lead to
No T cells
What do double negative thermocytes express to commit to T cell lineage
CD3 and CD5-adhesion and signaling molecules
Describe the role of Notch 1 and commitment to T cell lineage
Receptor for Notch 1 is on thymocytes, without notch 1 won’t transcribe for T cell lineage, once Notch 1 binds it cleaves repressors with proteases and activates T cell associated genes
What are the two T cell lineages
Gamma:delta
Alpha: beta
TCRs interact with linear peptides T or F
True
What do gamma:delta T cells express and where are they found
Express only CD3 and found in gut mucosa
What do Alpha:beta T cells express
CD4, CD8 and CD3
Which allele (gamma, delta or Beta) rearrangement increases likelihood to commit to T cell line
Beta allele rearrangement
What happens to T cells that do not make productive arrangements
Die by apoptosis
What percentage of T cells survive by making productive arrangement
2%
How many attempts do each B allele get to make successful rearrangement
2
How many total attempts for B chain rearrangements on chromosome
4
What genes are responsible for recombination
RAG1 and RAG2
Describe the steps in forming the Pre-T cell receptor
Ptalpha (invariant chain) checks the functionality of the Beta chain
If functional heterodimers form superdimer
Superdimer checks for interaction with CD3
Initiates rearrangement of alpha chain
Synthesizes CD8 and CD4
Proliferation of pre-T cell line
First T cell checkpoint
What genes are responsible for rearrangement of alpha chain in pre-t cells
RAG 1 and RAG2
What happens if rearrangement makes a functional alpha chain
Alpha chain is translocated into ER to check for interaction with B chain
Line proliferates
2nd T cell checkpoint
Combinatorial diversity
Separate rearrangement events for alpha and beta TCR chains so get diversity from that and how they interact, dictates antigen binding
Omenn syndrome
RAG deficiency lack T cells and B cells, opportunistic infections, must treat with bone marrow transplant or fatal
What is the first checkpoint in T cell development
After B genes rearrange
What is 2nd checkpoint for T cell development
After alpha genes rearrange
What is positive selection
Checks for TCR binding to MHC complexes
Weak or no binding- die
Strong moderate binding- live
Where does positive selection occur
Cortex of thymus
What determines CD4 and CD8 expression
Positive selection, receptor will either bind MHC I or MHCII
What is negative selection
TCR must recognize MHC complex but not bind too well, if it binds tightly to APC in thymus it undergoes apoptosis
At what point can a T cell migrate to secondary lymphoid organs
After undergoing negative selection and not tightly binding to MHC
What is CD28
Co-stimulatory molecule
What is CTLA-4
Inhibitory signal
What are the adhesions molecules in T cells
Integrins-LFA-1, VLA-4
Generation of mature T cells occurs in stages that are defined by ____
Certain proteins expressed on cell surface
What occurs in progenitor (pro-T cell) stage
Proliferation and initiation of somatic recombination of Beta chain
What occurs in precursor (pre-T cell) stage
Expression of B chain with surrogate alpha (pTalpha) and CD3 and zeta chains=Pre-TCR complex
What makes up the Pre-TCR complex
CD3 and zeta chains, PTalpha, Beta chain
What happens in double positive T cell stage
Alpha and beta chains successful rearranged and expressed along with CD3 and zeta chains as membrane bound BCR complex
Express CD4 and CD8
Positive and negative selection occurs
What happens in single positive T cell
Downregulation of either CD8 or CD4 and final maturation occurs
What happens a mature, naive T cell right after development ends
Released into circulation as single positive T cell
What happens when naive T cells encounter their antigen
Induce T cells to proliferate and differentiate, effector T cells perform function
How is delivery of antigen to lymphoid tissues aided by innate immunity
Dendritic cells deliver to lymphatic vessel, inflammation increases blood flow to infected sites as well as lymph