Micro I-11: Development Of T Cells

Front 1

Where do T cells develop?

Back 1

- in the thymus

Front 2

What are the two structural components that make up the thymus?
What cells populate this organ?

Back 2

- outer cortex and inner medulla
- cells of bone marrow origin (Lymphocytes (thymocytes), Dendritic cells, Macrophages)

Front 3

What cells does the cortex of thymus contain?
medulla?
Func of macrophages in both cortex and medulla?
Where is Hassall’s corpuscles located?
function?

Back 3

- immature thymocytes, branched cortical epithelial cells, and a few macrophages
- mature thymocytes, medullary epithelial cells, dendritic cells and macrophages.
- remove many thymocytes that fail to mature properly
- medulla of thymus
- site of cell destruction

Front 4

MOA of thymic involution?
How does involution affect T cell –mediated immunity?

Back 4

- Human thymus fully developed at birth -> Increases in size until puberty -> begins to atrophy -> Atrophy complete by 30 y/o
- Does not impair it -> Once established, T cell repertoire is long-lived and/or self-renewing

Front 5

Diff of life of T cell vs. B cell?

Back 5

- T cells are long-lived, B cells are short lived

Front 6

What are the five phases of T cell development?

Back 6

Phase 1: Arrival in the thymus and initial development
Phase 2: Positive selection
Phase 3: Negative selection
Phase 4: Entry to the peripheral T cell pool
Phase 5: Terminal antigen-stimulated differentiation into effector and memory cells

Front 7

Once arriving in thymus, what initial development occurs in T cells?

Back 7

- Expression of antigen receptor: (TCR) and co-receptors (CD4, CD8)

Front 8

What is the way for a ptn to be recognized by a T cell receptor?

Back 8

- ptn denatured and proteolytically degraded -> processed into peptide antigens -> peptide antigens bound to MHC molecules -> presented by T cell

Front 9

What are the components of T cell receptor complex?

Back 9

- TCR, CD3, epsilon chain

Front 10

How do the CD4 and CD8 glycoptns differ in structure?

Back 10

- CD4 has four extracellular Ig-like domains (D1-4) with hinge btwn D2 and D3. CD8 has an alpha and beta chain, connected at the stalk

Front 11

MOA of somatic recombination of TCR a loci?
b loci?

Back 11

- Va gene segment rearranges to Ja gene seg -> functional exon encoding Va domain
- rearrangement of Vb, Db, Jb gene seg -> functional V-domain exon.

Front 12

MOA of somatic recombination of TCR loci?

Back 12

- RAG complex and other DNA-modifying enzymes -> Recombinase recognizes recombination signal sequences (RSSs) that flank gene segments -> Junctional diversity generated at joints between gene segments

Front 13

MOA of development of ab (alpha-beta) T cells?

Back 13

- double neg T cells rearrange their g, d, and b genes -> signals thru pre-TCR switch off the g- and d-chain genes and commit the cell to a:b lineage -> rearrangement of TCRa chain creates mature a:b TCR receptor

Front 14

MOA of development of gd (gamma-delta) T cells?

Back 14

- double neg T cells rearrange their g, d, and b genes -> signals thru g:d TCR switch off the b–chain gene and commit the cell to the g:d lineage -> g:d T cell matures and migrates to periphery

Front 15

MOA of TCR co-receptor expression?

Back 15

- Vb-DJb rearrangement in frame -> beta-chain ptn produced -> surface expression of b chain with surrogate alpha chain -> b rearangement stops -> cell proliferates -> CD4/CD8 induction -> alpha transcription starts -> Va-Ja rearrangement surface expression of a:b:CD3 selective events begin

Front 16

What MHC molecules does the CD8 co-receptor bind to?
structure of MHC molecule? 
CD4 coreceptor? 
structure?

Back 16

- alpha3 domain of MHC class I
- a heavy membrane-bound heavy (or alpha) chain and noncovalently bonded Beta2-microglobulin
- beta2 domain of MHC class II molecules
- two membrane-bound chains, an alpha and beta chain

Front 17

What determines whether the T cell will become a CD4 or CD8 T cell?

Back 17

- Interaction of a double-positive T cell with a self-peptide:self-MHC complex (I or II) during positive selection in thymic cortex

Front 18

What happens when there is failure to recognize peptide-MHC complex on thymic epithelial cell by double positive thymocyte?

Back 18

- apoptotic cell death

Front 19

What happens in negative selection?
What is this process mediated by?
Where does this process occur?

Back 19

- Eliminates thymocytes that bind TOO STRONGLY to self-peptide:MHC by apoptotic death
- mostly by bone marrow-derived dendritic cells and macrophages
- mostly at cortico-medullary junction

Front 20

What is central tolerance?
What happens if there is a failure of central tolerance?

Back 20

- when only T cells that are tolerant of self antigens survive and are released to the mature T cell pool
- can lead to autoimmune disease

Front 21

What happens when thymocytes survive both positive and negative selection?

Back 21

- leave thymus in blood as mature single-positive CD4 or CD8 T cells and enter the circulation

Front 22

What do B and T cell neoplasias result in?

Back 22

- lymphomas and leukemias

Front 23

Wherer din the normal cell development stage does pre-B cell leukemia occur?
Location?
Status of Ig V genes?

Back 23

- Pre-B cell receptor
- Bone marrow and blood
- unmutated

Front 24

Where in the normal cell developmental stage does multiple myeloma occur?
Location?
Status of Ig V genes?
Lab?

Back 24

- Plasma cell; various isotypes
- Bone marrow
- mutated, no variability within clone
- monoclonal gammopathy