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51 Cards in this Set

  • Front
  • Back
Identify and characterize the structure of the thymus and its cellular components
1) Capsule
2) Subscapular region
3) cortex
4) medulla
List the factors that convert stem cells into thymocytes commited to the T cell lineage?
1) something with a 7
2) other things
3) thats all
Describe the sequence of events that lead to expression of an alpha beta T cell receptor
1) gene expression
2) gene rearrangements
3) double selection
4) self and non self
Distinguish the process of positive and negative selection of T cells in the thymus?
positively select those t cells with the right receptors
negatively select those that respond to self
Name the 7 structures of the thymus
1) capsule
2) trabeculae
3)subscapular epithelium
4) cortex
5) medulla
6) corticomedullary junction
7) Hassall's corpuscle
Name the cells of the thymus?
1) cortical epithelial cell - thymus
2) thymocyte (bone marrow
3) medullary epithelial cell from thymus
4) dendritic cell in medulla from bone marrow
4)macrophage in medulla from bone marrow
What is the critical signaling molecule for commitment to the T cell lineage?
notch 1 (first step, notch 1)
What are the phenotypic markers of the uncommited vs commited to T cell lineage?
CD 23 = uncommitted and germline TCR Genes
CD2, IL7 = committed and rearranging has begun
What are the 4 types of cells that thymocytes can develop into?
-gamma delta T cells
-alpha beta T cells (includes CD4/8)
-regulatory T cells
-NK t cells
Please describe the 10 steps of T cell development in the thymus?
1) progentor cells arrive in thymus via HEV in medulla (from bone marrow)
2) cell proliferation at corticomedullary junction
3) double negative T cells commit to T lineage in cortex
4) rearrange B genes
5) check point for pre TCR
6) proliferating double negative pre-T cells
7) immature double positive T cells away from dendritic cell
8) rearrange alpha genes
9) check point for TCR
10) mature into double positive cells at corticomedullary junction
What is the 7 step overview of T cell development in thymus?
1) commitment to T cell lineage
2) proliferation and differentiation into double positive CD 3+ thymocytes in subscapular region
3) Generation of TCR
4) Commitment to alphabeta or delta gamma lineage
5) positive selection of alpha beta TCR in cortex
6) Negative selection of alpha beta TCR at corticomedullary junction
7) export to peripheral secondary lymphoid tissues leave thymus via HEV
What are the two types of T cell receptor?
1) alpha:beta
2) gamma: delta
What are the steps and marking of the decision of the T cell to become either gamma delta?
1) CD34 uncommitted progenitor
2) CD2 commited double negative T cell progenitor
3) gamma and delta chains rearrange and recieves signal to stop rearrangement
4) make gamma delta TCR
What are the steps to become alpha:beta T cell?
1) CD 34 uncommited progenitor
2) CD 2 committed double negative progenitor
3) double negative T cells rearrange beta, gamma and delta loci
3) beta chain rearranges
4) pre TCR assembles
5) expression of CD 8 and CD 4
6) uncommitted double positive thymocyte with a b chain on the surfaec
What stage does the T cell make the decision to become a gamma delta or alpha beta t cell?
DN stage
What protein promotes recominbation of TCR genes?
How many attempts and chances are there to achieve a productive rearrangement of the loci of the T cell?
2 attempts
four chances
After gene rearrangement occurs what happens?
a productive beta chain pairs with a surrogate alpha chain
When do you get the transition of double negative to double positive?
when you are rearranging the alpha beta and gamma genes
What does recombination of the alpha locus always do to the possibility of becoming a gamma delta T cell?
rearrangement of alpha chain gene always eliminates the linked delta chain locus
What are the four steps of becoming alpha beta?
1) gene rearragenment at beta locus
2) expression of Beta
3) joining with surrogate alpha
4) alpha recombination deletes delta and you are committed to alpha beta
What happens during the positive seelction of alpha beta cells in the thymus?
1) weak or no binding to MHC - cell dies
2) strong or moderate binding cell lives
How dou you get from a double positive T lymphocyte to a single positive T lymphocyte?
binding of MHC, the MHC class you bind determines what kind of T lymphocyte you will be
What happens when you have a transgenic receptor restricted to MHCa and your stroma expresses MHCa?
single positive CD8 T cells
Where does negative selection take place?
near the corticomedullary junction
What happens with negative selection?
too tight binding - die
moderate binding - cells live
What drives negative selection?
What drives positive selection?
What is AIRE?
causes expression of several hundred tissue specific geens to be transcribed in subpopulation of epithelial cells of thymus. they can be bound during negative selection and thus help with autoimmunity
What is FoxP3 T-Reg cells and what do they do?
FoxP3 T-Reg cells help body with supressing response of self reactive CD 4 T cells
How do FoxP3 T reg cells help with self tolerance?
they interact with the same APC as the CD4 self reactive cell and supress it via cytokines
What are the characteristics of T cells that leave the thymus?
self restricted
self tolerant
single positive CD4 or CD8
Where do T cells go after they are done developing in the thymus?
secondary lymphoid tissue via HEV
What are the disorders of T cell development? (5)
1) DiGeorge syndrome
5) Common gamma chain deficiency
What is DiGeorge Syndrome and its cause?
thymus fails to develop
T cells are absent but B cells are made
What causes IPEX?
Immune dysregulation polyendocrinopathy, enteropathy, X linked Syndrome
-Caused by deficiency in FOXP3
-Mostly affects boys
-autoimmunity towards tissue esp gut, skin,, thyroid
What is APECED and what are its causes?
Autoimmune polyglandular syndrome type I
-AIRE gene deficient
-no autoimmunity
What is SCID and what causes it?
SCID is caused by problem with RAG and is caused by T cell deficiency
What is common gamma chain deficiency and what is its cause?
Common gamma chain receptor for cytokines Il2, IL4, IL7, IL9 is mutated
How does TCR undergo recombination?
using RSS sequence
What is an important difference between B cell and T cell diversity?
after T cell is stimulated with antigen there is no further rearrangements to it
What is the difference between binding sites for antigen between B cell and T cells?
1)T cells have single binding site for antigen
2) T cell also binds MHC
How many types of constant reginos are there in the T cell?
1 C alpha
2 C beta
What are the alpha and beta chain variable regions?
Beta has D and J and V
Alpha only has V and J
Are there more J loci on the alpha or beta locus?
alpha locus
What does a TCR need to be coexpressed with?
Which cells have more junctional diversity B or T?
Which cells have more total diversity B or T?
What are the 2 things a TCR must recognize?
Where does CD8 bind on MHC?
alpha 3
Where does CD4 bind on MHC?