Immunology Test 2 T Cell Development Flashcards

1. T-cell progenitors develop in the bone marrow and migrate to the thymus where T-cell precursors reaarange T cell receptor gene
2. Postivie and negative selection in the thymus: immature T cells that recognize self MHC recieve signals for survival. Those that interact strongly with self antigen are removed from the repertoire
3. Mature Tcells migrate to the peripheral lymphoid organs where they encounter foreign antigens and become activated
4. activated T cells proliferate and migrate into peripheral sites to eliminate infection

-MHC restriction
-t cell maturation in the thymus and activation in the periphery depend on MHC moleucles

1. MHc-restricted
2. not reactive to self antigens

-cortex (outer): dense with immature thymocytes, a few macrophages
-medulla (inner): presence of more mature thymocytes, macrophages, and dendritic cells(DCs)
-thymus begins to shrink after puberty, but T cells will continue to be made throughout lifetime

-thymic stromal cells (thymic epithelia) to become commmitted to T cell lineage
-depends on IL-7 and Notch signaling for survival and differentitation program

-as for B cells, T cell maturation depends on TCR gene rearrangment and expression of various transcription factors and cell surface markers

1. double-negative t cells start to rearrange their beta, gamma, and delta loci
2. if beta chain gene rearranges, a pre-TCR assembles. signals through pre-TCR stop rearrangement and induce proliferation and expression of CD4 and CD8 > pre-t cell resumes rearrangemtn of alpha, gamma, and dleta genes (another chance to become gamma/delta t cell)
3. (strong Erk) if gamma and delta genes rearrange, a gamma/delta receptor assembles. signals through gamma/delta TCR stop further rearrangements adn commit cell to gamma/delta lineage > the gamma/delta cell matures, leaves the thymus and migrates to peripheral tissues

-presence of 2-Cbeta gene regions, each with D and J gene segments, means that T cells have 4 chances to rearrange a TCr beta chain compared to 2 chances for B cell heavy chain loci

1. DN1 cells in thymus begin to proliferate and express CD25 (IL-2Ralpha chain)
2. during DN2 stage, the TCR beta, gamma, and delta chain genes begin to rearrange (cells that become gamma/delta cells diverge here
3. DN3 cells halt proliferation and express the TCR beta chain
4. DN3/DN4 cells express surface pre- cell receptor, TCR beta chain plus Pre-Talpha
5. pre-TCR singals for - proliferation and arrest of beta chain recombination (RAG1/2 are lowered); and then later the induced expression of both CD4 and CD*. this stage is called DP (double postiive) and comprises the majority of thymocytes
6. DN4>DP stage is a period of cell proliferation. eventually, proliferation ends, RAG1/2 protein increase again and TCRalpha chain is recombined

-selects thymocytes bearing receptors capable of binding self-MHc molecules, which results in MHC restriction
-TCR alpha chain is continually rearranged for the 3-4 days of cell lifespan until postive selection is completed (unlike BCR, TCR surface expression does not turn off gene recombination = no allelic exclusion)

-postive selection coordniates the expression of CD4 and CD8 with the specificty of the cell's TCR
-depends on strength of TCR signaling:
-if T cell is being selected by MHC class II, the re-expression of CD4 provides stronger/ssuttained signals (via Lck), induces exdpression of TF ThPOK
-if selected by MHC class I, re-expresssion of CD4 wil not enhance signaling; this weaker signal leads to CD8 commitment (without ThPOK, Runx3 is expressed leading to CD8 expression and developement

-selects against thymocytes bearing high-affinity receptors for self-MHC alone or self-MHc bound to self-peptide; this process results in self-tolerance

1. death by neglect: TCR does not recognize anything (apoptosis)
2. postive selection: TCR recognizes self-peptide/MHC at sufficient levels, but not too strongly
3. negative selection: TCR recognizes self-peptide/MHC too strongly (apoptosis)
-only about 2% of DP cells make it through selection process

-cortical epithelial cell mediates positive selestion
-dendritice cell mediates negative selection

-the strength (magnitude and duration) of TCR signaling