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��Bone Marrow
T cell progenitor cells leave before gene rearrangement can occur
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Thymus
positive and negative selection
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Peripheral lymphoid orgasns
encounter foreign antigens and are activated
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Migration to active sites
activated t cells migrate to site of infection to activate macrophages or kill host cells or b cell area
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Path of t cells
Born in bone marrow, travel to thymus to develop, once matured they circulate the secondary lymphoid tissues
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Why is the thymus a primary lymphoid tissue?
it is only involved in development, not directly fighting infection
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What does the thymus contain?
Thymocytes (immature T cells) and t cells, macrophages, dendritic cells, and thymic stroma (epithelial cell)
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Digeorge syndrome
thymic epithelium does not develop so there is no thymus
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Thymus cortex
Outer, close packed and consists of ECTOdermal cells; contain thymocytes and macrophages
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Thymus medulla
Inner, less dense consists of endodermal cells; contains theymocytes, dendritic cells, and macrophages
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Thymic anlage (early thymus)
the combination of the ectodermal cells early in development that is later colonized by progenitor cells from the bone marrow
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Involution
replacement of thymus tissue with fat tissue after puberty
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What occurs in the early stage of development?
- progenitor stem cells enter the thymus but do not have t cell markers
- stem cells persist in the thymus and start to aquire the correct receptors, adhesion molecules and signaling molecules (IL-7 is secreted by thymic stromal cells and helps develop t cells)
- begin to rearrange TCR genes
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DN thymocytes
have t cell characteristics but no CD4, CD8, CD3, or TCR
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IL-7
secreted by thymic stromal cells and binds to IL-7 receptor on CD34+ cells
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Notch 1 receptor
on thymocytes; binds to ligands on thymic epithelial cells
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What signals do IL-7 and notch 1 initiate?
they result in the removal of repressive transcription factors
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What occurs in the middle stage?
TCR gene rearrangement starts for DN thymocyte;Becomes a DP thymocyte when CD4 and CD8 are expressed due to beta rearrangement.
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pre-TCR
pTalpha holds the beta chain in place
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What composes the pre-TCR
pTalpha and beta
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What does the pre-TCR signal
the termination of arrangement
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What is the first checkpoint?
to determine if the beta chain has the potential to bind to alpha chains
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What happens if the pre-TCR passes the checkpoint?
it becomes a pre-T cell
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beta chain has how many chances to rearrange
4
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What happens with successful beta rearrangment?
pre-TCR formation and RAG shut down
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What segments does the alpha chain have?
V and J; has many j segments so successful rearrangment is likely
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what is excised during alpha rearrangment?
delta loccus
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What happens when the alpha chain is successfully rearranged?
it pairs with the beta chain and shuts down RAG
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Positive selection
Developing T cells that recognize self will be positively selected
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Negative selection
developing t cells that bind too tightly to self will be negatively selected
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What is the end result of positive and negative selection?
t cells will bind to self moderately well
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Single positive thymocyte
positive selection determines if a T cell will become CD4 or CD8 depending on which MHC it binds
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Regulatory T cells
CD4 t cell that binds self antigens and suppresses other CD4 T cells that can bind to the same APC
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Are there more CD4 or CD8 cells?
twice as many CD4
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Bone marrow transplant
GHD occurs when mature t cells from the donor attack the host
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Organ rejection
Host immune system attacks transplanted organ if rejected
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Immunotherapy
Tumor therapy- select, enrich and amplify TILs
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