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Immunology > B and T cell Development > Flashcards

B and T cell Development Flashcards

1
Q

What CD marks the first stage of B cell development? What is this cell?

A

CD34+ (pluripotent hematopoeitic stem cell)

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2
Q

What are the 2 main role of the one marrow stroma in the development of B cells?

A

Make contact with B cells via adhesin: ligand interactions; Produce growth factors for attached B cells

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3
Q

What is the earliest distinguishable B cell in the B lineage?

A

Pro-B cell

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4
Q

In what stage of B cell development does the first VDJ recombination take place? What Ig is produced?

A

Pro-B cell; Surface IgM

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5
Q

How does the principle of allelic exclusion apply to the development of B cells? Why is this necessary?

A

When pro-B cells undergo the first round of VDJ recombination to produce IgM, if the rearrangement is successful then the rearrangement on the second chromosome is stopped; If this process did not occur then a B cell could make and express 3 different Ig such that it couldn’t bind efficiently to multivalent antigens?

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6
Q

What is the first checkpoint of B cell development?

A

Once the mu H chain has been successfully produced, its ability to bind to light chain is tested through binding to a pre-B cell receptor/ surrogate receptor. If there is successful assembly then intracellular signaling is triggered and development continues- otherwise apoptosis

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7
Q

What forms the pre-B cell receptor?

A

VpreB and Lambda5

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8
Q

What event marks the transition of pro-B cell to pre-B cell?

A

If the mu H chains assemble with surrogate receptor successfully

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9
Q

What cellular events occur upon successful assembly of the mu H chain with the pre-B cell receptor?

A

Transcription of RAG genes stops, H cain rearrangement is shut off, and the pre-B cells go through several rounds of division

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10
Q

What is the order of Light chain rearrangement in the Pre-B cell?

A

Kappa first, then lambda

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11
Q

What is the second check point of B cell development?

A

The successful rearrangement of light chains and assembly with mu H chains to form an IgM surface receptor

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12
Q

What stage of B cell development follows the pre-B cell?

A

Immature B cells

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13
Q

What CD is specifically expressed by B-1 cells?

A

CD5

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14
Q

What is the predominant type of Ig produced by B-1 cells?

A

Low-affinity, polyspecific antibodies

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15
Q

Approximately what percent of immature B cells are reactive to self antigen?

A

~75%

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16
Q

What is receptor editing?

A

If an immature B cell binds to a multivalent self antigen it undergoes further light chain rearrangement for a 2nd chance at recognizing non-self antigen

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17
Q

Following receptor editing, if an immature B cell is still self-reactive, what happens?

A

The cell will continue rearranging until it can no longer and then it gives up and dies– clonal deletion

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18
Q

What is the dominant method for establishing B cell self-tolerance?

A

Clonal deletion

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19
Q

What is anergy? When does it occur with B cells?

A

When self-reactive B cells bind to monovalent antigens they do not undergo further light chain rearrangement or apoptosis, are signaled to express mostly IgD or non-functional IgM, and is unresponsive to antigen

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20
Q

What is central tolerance?

A

The outcome of loss of self-reactive B cells in the bone marrow

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21
Q

Only what kind of B cells can leave the bone marrow?

A

Non-self reactive or anergic

22
Q

How is peripheral tolerance established?

A

Once immature B cells leave the bone marrow, those that recognize self-antigen will undergo apoptosis or become anergic

23
Q

At the point when immature B cells enter circulation, what Ig molecules are expressed on the surface and what is the relative levels of expression of each?

A

High IgM and low IgD

24
Q

What happens if an immature B cell cannot enter 2ndary lymphoid tissue?

A

It dies

25
Q

At what point do immature B cells become mature B cells?

A

Entry into secondary lymphoid tissue

26
Q

Through what molecules do B cells home to HEV via a gradient of chemokines?

A

CCL21 and CCL19 chemokines which binds to CCR7 receptor on B cells

27
Q

Once in the secondary lymphoid tissue, to what specific area do B cells migrate? What stimulates this movement?

A

B cells further home to primary lymphoid follicles where follicular dendritic cells secrete CXCL13 chemokine

28
Q

Once within a primary lymphoid follicle, what happens if a mature B cell does not see antigen?

A

it re-enters circulation as a naive B cell

29
Q

What is the ‘secret of life’ for naive B cells?

A

Regular passage through primary follicles in 2ndary lymphoid tissue

30
Q

What events are prompted by naive B cells encountering specific antigen in secondary lymphoid tissues?

A

B cells are detained in the T cell area and are signaled by T cells to differentiate immediately into IgM plasma cells and migrate to nearby primary follicles, which then become a secondary lymphoid follicle containing a germinal center

31
Q

What events occur within germinal centers?

A

Isotype switching and affinity maturation

32
Q

True or False: All cells within a B cell tumor will have identical Ig rearrangement.

A

True

33
Q

At what age does the thymus begin to degenerate?

A

1 year old

34
Q

What are the two lineages of T cells defined by TCR type?

A

Alpha-beta T cells and gamma:delta

35
Q

At the point when T cells begin to undergo gene rearrangement, what kind of T cell is it?

A

Double negative T cell

36
Q

What determines whether or not a cell becomes a alpha-beta or gamma-delta T cell?

A

The beta, gamma, and delta chain all start rearrangement simultaneously- if the gamma and delta chains successfully rearrange first, then the cell become gamma:delta cells. If the beta chain wins, then it will become an alpha-beta cell

37
Q

Why is T cell chain rearrangement biased toward success of beta chain rearrangement?

A

There is only 1 rearrangement necessary vs. 2; there are 4 possible beta chain rearrangements

38
Q

What is the first T cell developmental checkpoint?

A

The beta chain is tested for its ability to bind to a surrogate light chain (pTalpha)- if the cell is successful at assembling the pre-T cell receptor it continues differentiation- if not, development stops

39
Q

What molecules make up the pre-T cell receptor?

A

Beta chain, surrogate light chain, CD3 complex, and the zeta chain

40
Q

At what point does a Pre-T cell form?

A

If a pre-T cell receptor successfully assembles

41
Q

What cellular events are stimulated by the successful assembly of the pre-T cell receptor?

A

Ceased expression of RAG genes, a short bout of proliferation, and expression of both CD4 and CD8

42
Q

What are double positive thymocytes?

A

Developing T cells within the thymus that express both CD4 and CD8 on their surface

43
Q

What is checkpoint 2 in T cell development?

A

If the alpha chain successfully rearranges before both gamma and delta, the alpha chain is tested for its ability to assemble with the beta chain and if it doesn’t- apoptosis

44
Q

What is positive selection of T cells?

A

Double positive cells are tested for their ability to recognize self-peptides: MHC on cortical epithelial cells- if binding occurs, a positive signal is sent to the thymocyte and continues maturation

45
Q

What happens if a TcR doesn’t bind to a peptide:MHC?

A

The alpha chain undergoes receptor editing

46
Q

What stimulates a double positive T cell to become either CD4+ or CD*+ T cells?

A

If the cell binds to self MHC I:self peptide, it will become CD8+; If it binds to MHC II:self-peptide, it will become CD4+

47
Q

What is negative selection of T cells?

A

Autoreactive, single-positive T cells are removed from circulation by binding self-antigens: MHC complexes on thymal dendritic cells in the medulla

48
Q

What does AIRE stand for? Where is it expressed? What is its importance?

A

Autoimmune Regulator Gene; Expressed in thymal medullar epithelial cells; It is a transcriptional activator that induces low-level expression of thousands of tissue specific antigen genes

49
Q

What results from absence/ nonfunctional AIRE?

A

Self-reactive T cells enter the periphery and attack cells in various tissues causing autoimmune polyendocrinopathy candidiasis

50
Q

How is central tolerance established in T cells?

A

T cells reactive with thymic antigens and those antigens induced by AIRE are eliminated.

51
Q

How is peripheral tolerance established in T cells?

A

T cells enter the periphery, and if it recognizes self-antigen will undergo anergy or activation-induced cell death

52
Q

What is the typical, healthy ratio of CD4+ : CD8+ T cells?

A

2:1

Immunology (13 decks)

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