Exam 2 - German - T Cell Development Flashcards
Tell me the overall life cycle of a T cell.
T-cell progenitors develop in the bone marrow and migrate to the thymus
Positive and negative selection happens in the thymus - Immature T cells that interact strongly with self antigen are removed from the repertoire
Mature T cells migrate to the peripheral lymphoid organs - Foreign antigens in periphery are detected and T cells are activated
Activated T cells migrate to sites of infection - Activated T cells proliferate and eliminate infection
What are thymocytes?
Developing T cells w/in the thymus
Gamma-delta T cells do what? 3 things.
Maintain tissue integrity
Do not express CD4 or CD4 co-receptors
Interact with NON-CLASSICAL receptors
CD4 T cells do what?
Helper T cells
Several subtypes: TH1, TH2, TH17, TFH, Treg
Regulate adaptive and innate immune function
INTERACT WITH MHC CLASS II
What do CD8 T cells do?
Cytotoxic T cells
Direct effector fx
INTERACT WITH MHC CLASS I
In what organ does a lot of T cell development occur?
THYMUS
W/in the thymus, T cells go where first?
Cortical epi cells (Cortex)
Where do developing thymocytes move after the cortex?
To the medulla (Medullary epi cells)
*Selections take place here
**Once it leaves the thymus, it is now a mature, naive T cell
T/F - Thymus involuted with age.
TRUE
Reduced T cell production
The thymus involutes, yet T cell-mediated immunity is not grossly affected. Why?
T CELLS HAVE LONG HALF LIVES
CD4 - 4.2 years
CD8 - 6.5 years
*Keep in mind that those are half-lives. Meaning that half of all the CD4 dies w/in 4.2 years. The other half persists even still
T cell progenitors don’t commit until they reach the _________.
Thymus
What two molecules are important leaders for T cell development?
IL-7 receptor - CD127
Notch1 - T cell transcription factor complex
What is the first TCR chain that is rearranged?
BETA chain
T/F - The gamma and the delta chains can rearrange at the same time that the beta chain rearranges.
TRUE
If the gamma and delta chains rearrange successfully, then what occurs?
The T cell will become a gamma-delta T cell
If the alpha chain rearranges successfully, what happens?
The T cell becomes an alpha-beta T cell
The ______ chain is similar to the ________ chain in B cell development.
Beta
Heavy
What is the first checkpoint in T cell development?
The beta chain interacting with a “surrogate alpha” chain
When do CD4 and CD8 begin their expression?
When the gene rearrangement occurs after the first checkpoint has been passed.
Up until right after the first checkpoint and pre-T cells are proliferating, what is that section called?
Double-negative
The double-positive region includes what?
Alpha, delta, and gamma rearrangement and the second checkpoint
Positive and Negative selection happen here as well
Tell me the route that T cell progenitor cells take in the thymus.
Proliferates in the medulla
Double-negative T cells commit to T lineage in cortex
Rearrange beta genes in the cortex
Hit first checkpoint in the medulla and proliferating double-negative pre-T cells
Immature double-positive cells and rearrangement of alpha genes and hit second checkpoint in the cortex
T/F - Gene rearrangement dictates T cell lineage.
TRUE
T/F - There is a greater likelihood that 1 chain will rearrange instead of 2 chains.
TRUE
Tell me the rough idea about rearrangement.
Beta, gamma, delta genes re-arrange first
Gamma or delta rearrangement suppresses beta and alpha
Gamma-delta T cells leave the thymus with little selection
Beta chain production drives CD4 and CD8 expression
-Double-positive
What initiates the alpha-beta lineage?
Beta-chain formation
1st - V-D-J —> ??
2nd - V-DJ —> ??
V-DJ
VDJ
When the beta-chain binds a surrogate alpha chain what assembles to help stabilize the complex?
CD3 complex
*Signaling drives further development
—RAG fx halts
—Proliferation happens
Alpha-chain rearrangement excludes what?
Gamma-delta T cells
T/F - Double negative thymocytes, no CD4 or CD8, but double positive thymocytes, both CD4 and CD8.
TRUE
______ and ________ _________ matures thymocytes.
Positive
Negative
Selection
Positive selection = ?
Functional TCR
Negative selection = ?
No self-antigen binding
What is the process of positive selection?
A cortical epithelial cell in the thymus presents self-peptide to alpha:beta cells.
If the T cell does NOT bind MHC, it will NOT get a survival signal, and it dies.
If the T cell DOES bind MHC, it does get a survival signal and it lives
—Cells have about 3 days to bind MHC or else they will die. Cells can also go back and rearrange the alpha chain and try to re-bind
—Binding turns off RAG 1/2 complex
Positive selection determines what?
CD4 or CD8 expression
This occurs 1st in T cell development, but 2nd in B cell development
Explain negative selection.
Dendritic cells and macrophages present self peptides
If tight binding, cell dies
If moderate binding, cell lives
This is central tolerance
*Following this, naive mature T cells can still undergo differentiation (e.g. CD4 subtypes)
How do naive T cells enter a draining lymph node? 2 ways
In the blood
In the afferent lymph from an upstream lymph node
