BIOL 435 Ch. 8 p.2 (T-Cell Development)

Question 1

mTEC

Answer 1

• medullary thymic epithelial cells
• strong=apoptosis
• strong to intermediate=T regulatory cell (T reg)
• weak=conventional T cell

Question 2

MHC restriction

Answer 2

-ensured by positive selection
-TCR bind MHC=DP to SP
>if MHC1=CD8
>if MHC2=CD4

Question 3

self tolerance

Answer 3

• ensured by negative selection (central tolerance)

- clonal deletion

Question 4

clonal deletion

Answer 4

• induction of apoptosis in cells with too strong anti-self signalling/binding
• remains best proven and common method of tolerance induction in the thymus

Question 5

do we delete all thymocytes reactive to tissue-specific Ag?

Answer 5

• no
• not all tissue types are in the thymus
• have the AIRE

Question 6

AIRE

Answer 6

• autoimmune regulator protein
• induces expression of many specific-tissue proteins in medullary TECT
• binds epigenetic marks on histones to recruit TFs
• new T-cells can be screened against these Ag safely in the thymus

Question 7

other methods of self-tolerance

Answer 7

1. Clonal arrest
2. Clonal anergy
3. Clonal editing

Question 8

clonal arrest

Answer 8

-autoreactive T-cells are prevented from maturing further

Question 9

clonal anergy

Answer 9

-autoreactive T-cells are inactivated, but not deleted

Question 10

clonal editing

Answer 10

-second or third chances at rearranging a non-self reactive TCR alpha-gene

Question 11

instructive model

Answer 11

• TCR/CD4 and TCR/CD8 coengagement generate unique signals

- signals generated ‘instruct’ the T-cells which lineage to fullly commit to

Question 12

stochastic model

Answer 12

• positively selected thymocytes randomly downregulated CD4 or CD8
• only cells with ‘correct’ co-receptor receive signals to continue development
• strength of signal and duration of signal from TCR/coreceptor

Question 13

kinetic signalling model

Answer 13

-cells commit to CD4 lineage if they receive a continuous signal
-cells commit to CD8 lineage if stimulation signal is interupted
>IL-7 promotes CD8 differentiation

Question 14

DP thymocytes commit to other lymphocytes

Answer 14

1. NKT cells
2. Intraepithelial lymphocytes (IELs)
3. Regulatory T cells
   * signal cues are unclear

Question 15

NKT cells

Answer 15

• express a TCR with an invariant TCR alpha chain
• interact with CD1 molecules presenting lipid Ags
• bridge between innate and adaptive

Question 16

IELs

Answer 16

• intraepithelial lymphocytes
• usually CD8+
• also have features of innate immune cells

Question 17

regulatory T cells

Answer 17

-CD4+ subset
-helps to quench adaptive immunity
-less than 1%
>5-10% of CD4+ thymocytes

Question 18

final maturation

Answer 18

• controlled by a cascade of events

- upregulation of Foxo1 TF

Question 19

Foxo1 TF upregulates

Answer 19

• molecules required to help T-cells leave the thymus
• molecules giving survival signals
• a chemokine (sphinoshine 1-phosphate) receptor that helps cells exit and move to lymph nodes

Question 20

recent thymic emmigrants (RTEs)

Answer 20

• T cells that have just exited the thymus

- not functionally mature yet

Question 21

T regulatory negatively regulate immune responses

Answer 21

• belong to subset of CD4 T-cells
• expression of FoxP3 TF
• developmental cues are unclear

Question 22

T-cells function to

Answer 22

1. Deplete local area of stimulating cytokines
2. Produce inhibitory cytokines
3. Inhibit APC activity
4. Directly kill T-cells (cytotoxicity)

Question 23

B and T cell development similarities

Answer 23

• rearrangement of gene segments
• screening process to avoid self-reactivity
• production of small subsets with discrete function
• production of larger general purpose subsets

Question 24

B and T cell development differences

Answer 24

-location of maturation and screening
-screen process used
>+ and - for T cells
>- for B cells
-specific arrangements and identities of gene segment recombination (ex. Ds)
-eventual outcomes of Ag receptor stimulatino

Question 25

outcomes of receptor stimulation

Answer 25

• T-cells: require presentation and differentiate into helper or killer subsets
• B-cells: require T-cell help and secret Ab