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Immunology > 11 - Lymphocyte Development > Flashcards

11 - Lymphocyte Development Flashcards

1
Q

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

A

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

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2
Q

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

A

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

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3
Q

What are the 2 requirements of T-cell receptors?

A

self-tolerant | restricted to self-MHC

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4
Q

What does self-tolerant mean?

A

doesn’t react with self-peptide

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5
Q

Where does T-cell development occur in?

A

thymus

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6
Q

Where does early T-cell precursor development occur in?

A

bone marrow

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7
Q

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

A

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

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8
Q

What are thymocytes?

A

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

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9
Q

What is the positive stage of T-cell development?

A

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

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10
Q

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

A

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

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11
Q

Which stage does TCR gene segment recombination happen?

A

double-negative stage

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12
Q

What are mature naive T-cells?

A

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

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13
Q

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

A

early thymocyte development | T-cell maturation

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14
Q

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

A

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

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15
Q

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

A

positive selection | negative selection | lineage committment

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16
Q

What is positive selection?

A

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

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17
Q

What is negative selection?

A

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

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18
Q

What is lineage commitment?

A

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

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19
Q

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

A

the Notch receptor

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20
Q

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

A

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

21
Q

What is the receptor for IL2?

A

CD25 and IL2R

22
Q

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

A

positive selection

23
Q

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

A

negative selection

24
Q

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

A

double-positive form expressing both CD4+ and CD8+

25
Q

What are cortical thymic epithelial cells (cTEC)?

A

cells expressing high levels of MHC classes I and II

26
Q

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

A

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

27
Q

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

A

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

28
Q

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

A

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

29
Q

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

A

kept and move onto lineage commitment step

30
Q

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

A

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

31
Q

What is central tolerance? Where does it happen?

A

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

32
Q

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?

A

AIRE protein

33
Q

What is the AIRE (autoimmune regulator) protein?

A

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

34
Q

What is mTEC?

A

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

35
Q

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

A

clonal deletion via apoptosis

36
Q

What is peripheral tolerance?

A

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

37
Q

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

A

by suppressing or putting a break on immune responses

38
Q

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

A

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

39
Q

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

A

“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

40
Q

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

A

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

41
Q

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

A

novel and unique antigen receptor

42
Q

What are stromal cells?

A

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

43
Q

What is B220+?

A

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

44
Q

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

A

IgM

45
Q

How are B-cells selected?

A

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

46
Q

What is receptor editing in immature B-cell development?

A

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

47
Q

Where does central tolerance for B-cells occur in?

A

bone marrow (clonal deletion and receptor editing)

48
Q

What is the PALS area in lymphoid tissue?

A

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

Immunology (15 decks)

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