B-Cell and T-Cell Maturation - Diebel Flashcards

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1
Q

Where does B-Cell development occur?

A

Bone Marrow, does not require antigen

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2
Q

What are the components of the BCR?

A

Membrane bound IgM

CD79a and CD79b

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3
Q

What do Early Pro-B-Cells express?

A

TdT and c-Kit

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4
Q

What do Intermediate Pro-B-Cells express?

A

TdT and CD45R

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5
Q

What do Late Pro-B-Cells express?

A

CD45R and downregulated TdT, CD43, and RAG

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6
Q

What is CD45R?

A

Receptor for cell growth and differentiation on B-cell for lyfe

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7
Q

What cytokine helps to promote B-Cell lineage?

A

IL-7

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8
Q

What do pre-B-Cells express in the cytoplasm?

A

Igu heavy chains

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9
Q

What Ig to Immature B-cells express?

A

IgM (successful rearrangement of light chain genes)

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10
Q

What Ig’s do Mature B-Cells express?

A

IgM and IgD on surface

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11
Q

What is important for the survival from transition stage onward for B-Cells?

A

Blys (B-lymphocyte stimulator) and its receptor BR3

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12
Q

What are the 3 signaling molecules required for initiating the B-Cell differentiation process?

A

IL-4
IL-3
L-BCGF (Low Molecular Weight B-Cell Growth Factor)

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13
Q

Describe the immunodeficiency XLA

A

Caused by a mutation in the gene for enzyme Bruton’s Tyrosine Kinase (Btk)
Very few circulating B-cells and Ig
A form of agammaglobulinemia

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14
Q

Describe common variable immunodeficiency (CVID)

A
Reduced serum Ig, memory B-cells, class switch recombination and B-cell activation
Mutations in CD40L on T-Cells, B-Cell CD19, activated T-Cell co-stimulatory molecule ICOS, and TACI
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15
Q

How do B-Cells undergo Negative Selection?

A

Immature B-Cells that express IgM recognizing self-antigen will undergo apoptosis or light chain editing

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16
Q

Describe Follicular (B-2) B-Cells

A
Found in secondary lymphoid organs
Highly diverse BCR
T-Dependent activation
IgM and IgD
CD19/21 and CD23
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17
Q

Describe B-1 B-Cells

A
Found in peritoneal and pleural cavities
Self-renewing without signaling
T-Independent
IgM and CD5
Innate functioning B-Cells
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18
Q

What are TI-1 Antigens?

A

Prototypical bacterial cell wall components and LPS that can independently activate immature or mature B-cells without T-cell help

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19
Q

What are TI-2 Antigens?

A

Large polysaccharide molecules with repeating antigenic determinants that can independently activate mature B-cells without T-cell help

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20
Q

What do TI antigens, primarily PAMPs that can be recognized by TLRs, activate?

A

B-1 B-Cells

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21
Q

How do B-1 B-Cells bind LPS?

A

TLR4 through non-specific polyclonal activation

BCR through specific clonal activation

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22
Q

What is produced in response to B-1 B-Cells binding TI-1 antigen?

A

IgM

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23
Q

How do B-1 B-Cells bind TI-2 antigen?

A

Cross-Linking BCR through specific clonal activation

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24
Q

What is produced in response to B-1 B-Cells binding TI-2 antigen?

A

IgM

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25
Q

What is released by Th2 T-Cells to drive B-Cell proliferation and differentiation?

A

IL-2
IL-4
IL-5

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26
Q

T-Cell CD28 binds to…

A

B-Cell CD80/CD86 to prevent anergy

27
Q

T-Cell CD40L binds to…

A

B-Cell CD40

28
Q

T-Cell CTLA-4 binds to…

A

B-Cell CD80/CD86 causing downregulation

29
Q

T-Cell LFA-1 binds to…

A

B-Cell
ICAM-1
ICAM-3

30
Q

What do thymic stromal cells produce that are essential to T-cell development?

A

Notch

31
Q

What is positive selection of T-cells?

A

T-cells must recognize MHC Class I or MHC Class II molecules (self-restriction) with intermediate affinity

32
Q

What is negative selection of T-cells?

A

T-cells that recognize self-antigens bound to MHC II are killed (T-cells need to be tolerant to self-antigens)

33
Q

How else are T-Cells selected besides positive and negative selection?

A

Will only recognize your MHC complexes that are genetically identical to self.

34
Q

Double Negative Thymocytes

A

CD4-8-

35
Q

What is T-Cell CD44 required for?

A

Localization to Thymus

36
Q

What is T-Cell c-Kit required for?

A

Repliation

37
Q

What is T-Cell CD25 (IL-2R) required for?

A

IL-2 driven replication

38
Q

What is the function of Effector CD4+ T-cells?

A

Activation of Macrophages and B-Cells

39
Q

What is the function of CD8+ T-cells?

A

Killing of infected “target cells” and macrophage activation

40
Q

What is the Instructive Model for CD4+8+ selection for a single positive molecule?

A

CD8 Engagement Signal –> CD8+ or CD4 Engagement Signal –> CD4+

41
Q

What is the Stochastic Model for CD4+8+ selection for a single positive molecule?

A

Low CD4 in environment and able to bind MHC Class I –> CD8+ T-Cell
Low CD8 in environment and able to bind MHC Class II –> CD4+ T-Cell

42
Q

What is the Kinetic Signaling Model for CD4+8+ selection for a single positive molecule?

A

Low CD8 Engagement Signal

  • -> Continuous TCR signal –> CD4+ T-Cell OR
  • -> Disrupted TCR signal + IL-7 –> CD8+ T-Cell
43
Q

What 3 signals are required for activation of naive T-Cells?

A

TCR Signaling
Costimulatory Interactions
Cytokine Signaling (Autocrine IL-2 or Paracrine IL-12)

44
Q

Activation of many T-Cells through Superantigens binding to MCH II and TCRs creates over induction of what to cause toxic shock?

A

IFN-y

TNF-a

45
Q

Th1 CD4+ T-Cells are polarized by:

A

IL-12
IL-18
IFN-gamma

46
Q

Th1 CD4+ T-Cells effector cytokines produced:

A

IGN-gamma (pro-inflammatory & chemotactic for monocytes/macrophages)
TNF

47
Q

What master transcription factor generates cytokines in Th1 T-cells?

A

T-Bet

48
Q

What is the main function of Th1 T-cells?

A

Recognize antigen and make lymphokines to attract M1 macrophages to attack a serious infection

49
Q

Th17 CD4+ T-Cells are polarized by:

A

TGF-Beta
IL-1
IL-6
IL-23

50
Q

Th17 CD4+ T-Cells effector cytokines produced:

A

IL-17

IL-22

51
Q

What master transcription factor generates cytokines in Th17 T-cells?

A

ROR-gamma-t

52
Q

What is the main function of Th17 T-cells?

A

Cause Inflammation; more powerful that Th1; cause severe autoimmunity through IL-17

53
Q

Th2 CD4+ T-Cells are polarized by:

A

IL-4

54
Q

Th2 CD4+ T-Cells effector cytokines produced:

A

IL-4
IL-5
IL-13

55
Q

What master transcription factor generates cytokines in Th2 T-cells?

A

GATA3

56
Q

What is the main function of Th2 T-cells?

A

Alternatively Activates M2 Macrophages to wall-off parasites/pathogens and promote healing; IL-4 attracts eosinophils

57
Q

Follicular Helper Tfh CD4+ T-Cells are polarized by:

A

IL-6

IL-21

58
Q

Follicular Helper Tfh CD4+ T-Cells effector cytokines produced:

A

IL-4

IL-21

59
Q

What master transcription factor generates cytokines in follicular helper Tfh T-cells?

A

Bcl-6

60
Q

What is the main function of the follicular helper Tfh T-cells?

A

Stimulated by antigen to migrate from T-cell areas of lymph nodes into the B-cell follicles, where B-cells are activated and undergo class switching

61
Q

Treg CD4+ T-Cells are polarized by:

A

IL-2

TGF-Beta

62
Q

Treg CD4+ T-Cells effector cytokines produced:

A

IL-10

TGF-Beta

63
Q

What master transcription factor generates cytokines in Treg T-cells?

A

FOXP3

64
Q

What is the main function of the Treg T-cells?

A

Suppress activation and function of all other T-cells; known as antihelpers