11 - Lymphocyte Development

Question 1

Immature T-cells entering the thymus are __________ to becoming __________ and _______________.

Answer 1

are not yet committed to becoming a lymphocyte and express no antigen specific receptors and co-receptors

Question 2

T-cells leaving the thymus are _____ T-cells and _______.

Answer 2

mature and functional T-cells and express unique & specific antigen-specific T-cell receptors and co-receptors

Question 3

What are the 2 requirements of T-cell receptors?

Answer 3

self-tolerant | restricted to self-MHC

Question 4

What does self-tolerant mean?

Answer 4

doesn’t react with self-peptide

Question 5

Where does T-cell development occur in?

Answer 5

thymus

Question 6

Where does early T-cell precursor development occur in?

Answer 6

bone marrow

Question 7

What is the double negative stage of T-cell development?

Answer 7

thymocyte is not expressing both T-cell receptor and co-receptor

Question 8

What are thymocytes?

Answer 8

T-cells that have not been differentiated and committed yet to T-cell development

Question 9

What is the positive stage of T-cell development?

Answer 9

thymocyte expresses BOTH T-cell receptor and BOTH CD4 and CD8 co-receptors

Question 10

What is the single positive stage of T-cell development?

Answer 10

T-cell will be single positive and be committed to specific subset either CD4 or CD8, not both

Question 11

Which stage does TCR gene segment recombination happen?

Answer 11

double-negative stage

Question 12

What are mature naive T-cells?

Answer 12

T-cells that are committed to either CD4 or CD8 but have not came across antigen and have not been activated

Question 13

What are the 2 main stages in which T-cell development occurs in?

Answer 13

early thymocyte development | T-cell maturation

Question 14

What are the 3 events that happen during early thymocyte development?

Answer 14

hematopoietic precursors commit to T-cell lineage | TCR gene recombination | expansion of thymocyte post-recombination

Question 15

What are the 3 events that happen during T-cell maturation?

Answer 15

positive selection | negative selection | lineage committment

Question 16

What is positive selection?

Answer 16

choose T-cells that can recognize self-MHC and binds to it with low affinity

Question 17

What is negative selection?

Answer 17

remove T-cells recognizing self-protein or have a high affinity to self-MHC

Question 18

What is lineage commitment?

Answer 18

T-cells commit to either CD4 or CD8 and become effector cells

Question 19

What commits hematopoietic stem cells to the T-cell lineage?

Answer 19

the Notch receptor

Question 20

What is the beta selection step in the negative stage during early thymocyte development?

Answer 20

tests the pre-TCR to see if it is signaling correctly == full functioning receptor&raquo_space;> cell will undergo proliferation

Question 21

What is the receptor for IL2?

Answer 21

CD25 and IL2R

Question 22

Which step during T-cell maturation ensures that the T-cell is restricted to self-MHC?

Answer 22

positive selection

Question 23

Which step during T-cell maturation ensures that the T-cell is self-tolerant?

Answer 23

negative selection

Question 24

At what “form” are the T-cells entering T-cell maturation?

Answer 24

double-positive form expressing both CD4+ and CD8+

Question 25

What are cortical thymic epithelial cells (cTEC)?

Answer 25

cells expressing high levels of MHC classes I and II

Question 26

What are the 3 outcomes when T-cells encounter self-peptide/MHCs? What are the percentages for each outcome?

Answer 26

can't bind (90-96%) | bind too strongly (2-5%) | bind just right (2-5%)

Question 27

What happens to the T-cell if it cannot bind to any MHC?

Answer 27

no interaction stimulating these receptors to stay alive = deleted by neglect

Question 28

What happens to the T-cell if it binds too strongly to MHC/self-peptide?

Answer 28

suggests it will be self-reactive = will be negatively selected against = cell dies via apoptosis

Question 29

What happens to the T-cell if it binds just right to MHC?

Answer 29

kept and move onto lineage commitment step

Question 30

Why will lineage commitment happen during positive selection? What is it testing?

Answer 30

testing whether TCRs are binding to MHC | the MHC T-cells bind to the best = suggests the co-receptor it is expressing that is stabilizing the interaction | this can shift the T-cell from DP to SP

Question 31

What is central tolerance? Where does it happen?

Answer 31

negative selection = establishing self-tolerance in T-cells | thymus and primary lymphoid organs

Question 32

How do we get all of the self-protein to be expressed and presented to TCRs to make sure it doesn't react with other organs?

Answer 32

AIRE protein

Question 33

What is the AIRE (autoimmune regulator) protein?

Answer 33

turns on transcription factors of all of our genes | expressed in the mTEC

Question 34

What is mTEC?

Answer 34

expresses AIRE protein and ensures that all of the proteins in our bodies are expressed

Question 35

How are T-cells that are binding to MHC on mTEC deleted?

Answer 35

clonal deletion via apoptosis

Question 36

What is peripheral tolerance?

Answer 36

self-tolerance that can happen outside of the primary lymphoid organ

Question 37

How does T-reg keep T-cells in check?

Answer 37

by suppressing or putting a break on immune responses

Question 38

What are the 4 ways T-reg cells negatively regulate immune responses?

Answer 38

deplete cytokines stimulating cells (via IL2R or CD25) | produce inhibiting cytokines (IL10) | inhibit APC activity | directly kill T-cells

Question 39

What are 3 peripheral mechanisms of tolerance that protect against autoreactive thymocytes?

Answer 39

"hidden" self-antigens are due to APCs lacking correct co-stimulatory molecule needed to initiate immune response | self-antigens presented by non-APCs = prevents initiation of autoimmunity | T-cells become anergic due to absence of co-stimulation

Question 40

What are the 7 defining characteristics of T-cell selection/development?

Answer 40

negative selection | positive selection | lineage commitment | T-cell commitment = Notch | TCR gene recombination | thymus | different subsets

Question 41

Each B-cell circulating in the boy express a ____.

Answer 41

novel and unique antigen receptor

Question 42

What are stromal cells?

Answer 42

microenvironment that helps B-cells develop | in the bone marrow

Question 43

What is B220+?

Answer 43

marker for pre-pro B-cells (they develop this signal)

Question 44

What antibody is first expressed on every B-cell post-genetic recombination?

Answer 44

IgM

Question 45

How are B-cells selected?

Answer 45

negative selection ONLY against self-protein = clonal deletion stage | (no positive selection because no MHC molecule interaction needed)

Question 46

What is receptor editing in immature B-cell development?

Answer 46

if receptor is reacting a little bit with self-protein = light chain of receptor will be edited

Question 47

Where does central tolerance for B-cells occur in?

Answer 47

bone marrow (clonal deletion and receptor editing)

Question 48

What is the PALS area in lymphoid tissue?

Answer 48

the T-cell zone in the lymphoid tissue where B-cells interact with T-helper cells that will help finish its maturation stage