EXAM 2 T Cells: Development

Question 1

T cell progenitors develop in the ___ and migrate to the ___

Answer 1

bone marrow, thymus

Question 2

positive and negative selection occurs in the ___

Answer 2

thymus

Question 3

mature T cells migrate to the ___

Answer 3

peripheral lymphoid organs

Question 4

activated T cells migrate to ___

Answer 4

sites of infection

Question 5

T-cell precursors rearrange their T cell receptor genes in the ___

Answer 5

thymus

Question 6

immature T cells that recognize ___ receive signals for survival. those that interact ___ with self antigen are removed from the repertoir.

Answer 6

self MHC, strongly

Question 7

mature T cells encounter ___ in the peripheral lymphoid organs and are ___

Answer 7

foreign antigens, activated

Question 8

___ are developing T cells within the thymus

Answer 8

thymocytes

Question 9

describe gamma delta T cells

Answer 9

• maintain tissue integrity
• do not express CD4 or CD8 co-receptors
• interact with non classical receptors

Question 10

describe CD4 T cells

Answer 10

• helper T cells
• several subtypes: Th1, Th2, Th17, Tfh, and Treg
• regulate adaptive and innate immune function
• interact with MHC class II

Question 11

describe CD8 T cells

Answer 11

• cytotoxic T cells
• direct effector function
• interact with MHC class I

Question 12

the ___ is the site of all T cell development

Answer 12

thymus

Question 13

TCR development occurs within the ___ of the thymus

Answer 13

cortex

Question 14

positive and negative selection occurs as thymocytes move from ___ to ___

Answer 14

cortex to medulla

Question 15

what happens to the thymus as you age?

Answer 15

it involutes

Question 16

what are the half lives of CD4 and CD8 T cells?

Answer 16

• CD4 T cells - 4.2 years
• CD8 T cells - 6.5 years

Question 17

the thymus involutes with age, resulting in reduced T cell production, but T cell-mediate immunity is not grossly affected. why?

Answer 17

the long life span of individual T cells and diversity of TCRs is sufficient to provide immunity even after the loss of T cell production as the thymus involutes with age

Question 18

T cell progenitors don’t commit until they reach the ___

Answer 18

thymus

Question 19

give an overview of T cell development, including check points

Answer 19

Question 20

thymic location influences ___

Answer 20

T cell development

Question 21

describe how thymic location influences T cell development

Answer 21

Question 22

describe how gene rearrangement dictates T cell lineage

Answer 22

• beta, gamma, and delta genes rearrange 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

Question 23

___ formation initiates the ___ lineage

Answer 23

• beta chain
• alpha:beta

Question 24

describe how beta chain formation initiates the alpha:beta lineage

Answer 24

Question 25

beta chain rearrangement forms the \_\_\_

Answer 25

pre-TCR

Question 26

describe beta chain rearrangement

Answer 26

* occurs first * four attempts * two attempts per locus * two genes * the beta chain locus is organized differently than immunoglobulin chains 1. Vbeta - Dbeta - Jbeta → Vbeta - DJbeta 2. Vbeta - DJbeta → VDJbeta

Question 27

describe how beta chain rearrangement forms pre-T cells receptors

Answer 27

* first checkpoint * beta chain binds a surrogate alpha chain analogue (pTalpha) * assembles CD3 complex * signaling drives further development * RAG function halts * proliferation

Question 28

alpha chain rearrangement occurs in \_\_\_

Answer 28

pre-T cells

Question 29

the alpha chain locus can sustain many attempts at a \_\_\_

Answer 29

functional rearrangement

Question 30

describe alpha chain rearrangement

Answer 30

* occurs in pre-T cells * follows proliferation and CD4/8 expression * may still develop into gamma:delta T cells * alpha chain rearrangement excludes gamma:delta T cells * rearrangement of an alpha chain gene always eliminates the linked delta chain locus

Question 31

which thymocyte has no CD4 or CD8?

Answer 31

double negative thymocytes

Question 32

which thymocytes have both CD4 and CD8?

Answer 32

double positive thymocyte

Question 33

\_\_\_ and ___ matures thymocytes

Answer 33

positive and negative selection

Question 34

what do positive selection and negative selection do?

Answer 34

* positive selection - functional TCR * negative selection - no self-antigen binding

Question 35

describe positive and negative selection that matures thymocytes

Answer 35

Question 36

\_\_\_ selection ensures MHC is bound

Answer 36

positive

Question 37

during positive selection, ___ cells present MHC I/II: self-peptide complexes. ___ must bind MHC within 3-4 days (alpha chain rearrangement can occur, and binding turns off RAG1/2 complex). weak or no binding of TCR to MHC results in \_\_\_, whereas moderate or strong binding results in \_\_\_. this is the ___ checkpoint.

Answer 37

* epithelial * TCR * apoptosis * survival * second

Question 38

\_\_\_ selection determines CD4 or CD8 expression

Answer 38

positive

Question 39

\_\_\_ selection prevents self-antigen binding

Answer 39

negative

Question 40

during negative selection, ___ and ___ present self peptides. moderate binding allows the T cell to \_\_\_. excessive binding induces \_\_\_.

Answer 40

* dendritic cells and macrophages * live * apoptosis

Question 41

following selection, T cells are considered \_\_\_. at this point, they can still undergo \_\_\_

Answer 41

* naive and mature * differentiation

Question 42

mature, naive T cells enter the \_\_\_

Answer 42

blood stream they enter a draining lympho node by two routes: in the blood or in the afferent lymph coming from an upstream lymph node

Question 43

\_\_\_ is the signaling component of the TCR

Answer 43

CD3

Question 44

cortical epithelial cells in the thymus release \_\_\_, which is a signaling molecule that tells T cells that they are in the right spot and induces responsivity to \_\_\_. these signals allow a ___ to become a \_\_\_.

Answer 44

* notch1 - T cell transcription factor complex * IL-7 * these signals allow an uncommitted T cell progenitor to become a double negative thymocyte committed to the T-cell lineage

Question 45

during beta rearrangement, what happens if delta:gamma rearrangement happens before beta rearrangement?

Answer 45

the T cell will become a delta:gamma T cell the same is true for alpha rearrangement - if delta:gamma rearrangement occurs before alpha rearrangement, it will be come a delta:gamma T cell delta:gamma T cells are not as common as alpha:beta

Question 46

during beta chain rearrangement, which protein is turned off to allow for proliferation?

Answer 46

RAG it is then turned back on after proliferation