module 03 section 05 (T-cell maturation)

Question 1

define “stem cell”

Answer 1

undifferentiated, self-renewing, pluripotent cell that undergoes mitotic division to generate a stem cell and a progenitor cell

Question 2

define “progenitor cell”

Answer 2

gives rise to several but not all hematopoietic lineages where it loses the ability of self-renewal (commited to the generation of a cell lineage)

Question 3

define “precursor”

Answer 3

cell that is restricted to a single lineage (e.g. T-cell or B-cell lineage)

Question 4

which type of cells are progenitor T-cells derived from?

Answer 4

bone marrow stem cells

Question 5

where to progenitor T-cells migrate for maturation?

describe this

Answer 5

thymus (midline of the body above the heart, made up of lobules)

Question 6

the lack of a thymus in humans clinically manifests as what disease?

Answer 6

DiGeorge’s syndrome

Question 7

how are individuals of DiGeorge’s syndrome characterized?

Answer 7

by birth defects including cleft palate, no philtrum (vertical groove in the middle upper lip), and wide-set eyes

Question 8

what happens to the thymus with age? during pregnancy?

Answer 8

shrinks (reverts back after pregnancy)

Question 9

what is contained by each lobule of the thymus?

Answer 9

discrete cortical and medullary regions

Question 10

where do progenitor T-cells enter the thymus?

Answer 10

at the cortical region

Question 11

where do the final steps of progenitor T-cell maturation occur (what part of the thymus)?

Answer 11

move from the cortical region to the medullary region to mature

Question 12

the coritcal region of the thymus is comprised of a large number of:

Answer 12

thymocytes: immature T-cells located in the thymus

Question 13

what, in terms of T-cell maturation, occurs in the cortical region?

Answer 13

gene rearrangement and the first step of double selection

Question 14

what is the corticomedullary junction?

Answer 14

border btwn the cortical and medullary regions

Question 15

what, in terms of T-cell maturation, occurs in the corticomedullary junction?

Answer 15

second step of the double selection process

Question 16

is there a high or low population density of thymocytes in the medullary region?

Answer 16

low

Question 17

what, in terms of T-cell maturation, occurs in the medullary region?

Answer 17

thymocyte maturation, which eventually results in mature single positive (CD4 or CD8) T-cells

Question 18

how many steps are involved in the differentiation and proliferatoin of progenitor cells into mature T-cells?

Answer 18

5

Question 19

what is step 1 of differentiation and proliferatoin of progenitor cells into mature T-cells?

what are cells at this stage called? why?

do cells at this stage express CD3 molecules or TCR on their surface?

Answer 19

• progenitor T-cells migrate to the thymus
• double negative, because they dont express CD4 or CD8
• no

Question 20

commited progenitor T-cells are characterized by several surface markers, what are they? (3)

Answer 20

Thy-1low (thymus)
Lin+ (lineage)
Sca-1+ (stem cell antigen-1)

Question 21

what is step 2 of differentiation and proliferatoin of progenitor cells into mature T-cells?

what is expressed at this step?

what are thymocytes at this stage called? why?

Answer 21

• progenitor T-cells undergo TCR gene rearrangement that leads to the formation of an immature αβ or γδ T-cell
• at this step thymocytes express a functional TCR-CD3 complex
• cells at this stage are called double positive, as they express both CD4 and CD8

Question 22

what are the first type of T-cells to arise during embryonic development?

Answer 22

cells expressing particular γδ genes (intraepithelial lymphocytes)

Question 23

there are 3 waves of embryonic TCR-γδ T-cells during fetal development, explain the 1st

Answer 23

the first wave of TCR-γδ T-cells produced in the fetus migrate to the epidermis

Question 24

there are 3 waves of embryonic TCR-γδ T-cells during fetal development, explain the 2nd

Answer 24

the second wave of TCR-γδ T-cells produced in the newborn migrate to the reproductive epithelium

Question 25

there are 3 waves of embryonic TCR-γδ T-cells during fetal development, explain the 3rd

Answer 25

the third wave of TCR-γδ T-cells produced in adults results in their migration to the intestinal epithelium, skin, airway tract and uterus

Question 26

what is step 3 of differentiation and proliferatoin of progenitor cells into mature T-cells?

Answer 26

- pos selection is the first mechanism of double selection - thymocytes interact with APCs in the cortical region - they then commit to CD8 or CD4 depending on if they interact with MHC class I or MHC class II complex of cortical epithelial cells, respecitvely - if the thymocytes don't interact with cortical epitelial cells - they die by apoptosis

Question 27

what is step 4 of differentiation and proliferatoin of progenitor cells into mature T-cells?

Answer 27

- neg selection is the second mechanism of double selection - the newly committed T-cells have migrated to the corticomedullary region and may recognize APCs expressing MHC-self-antigen complexes - if the T-cell interacts with these it dies by apoptosis - if it doesn't, it migrates to medullary region for final step of maturation

Question 28

what is step 5 of differentiation and proliferatoin of progenitor cells into mature T-cells?

Answer 28

- TCR-αβ CD3(high) on the T-cell engages with antigen peptide MHC class I or II to become fully committed to single positive CD4 or CD8 T-cell lineage - after completion of maturation, the single positive cell migrates to the periphery

Question 29

CD4+ T-cells are the: | what type of T-cell

Answer 29

helper T-cells

Question 30

CD8+ T-cells are the: | what type of T-cell

Answer 30

cytotoxic T-cells