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IHO Week 4 - WLB > B-cell and T-cell Maturation - Diebel > Flashcards

B-cell and T-cell Maturation - Diebel Flashcards

1
Q

What two phenotypic markers are expressed in the stem cell stage of B-cell development?

A
  • CD34
  • c-kit
    • binds to stem-cell factor expressed on bone marrow stromal cells
    • induces the pro-B cells to proliferate and differentiate into precursor B cells (pre-B cells)
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2
Q

What is a stem cell B-cell doing in the bone marrow as it is developing into an immature transitional B-cell?

A
  • rearrange the genes for their heavy and light chains
  • synthesize cell surface IgM
    • acts as initial antigen receptor (BCR)
      • membrane-bound immunoglobulin (mIgM)
      • signaling chains CD79a & CD79b
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3
Q

When does a B-cell begin to express TdT?

A
  • Progenitor B-cell stage (pro-B cell)
    • earliest stage of antigen-independent B-cell development
      • early pro-B cells express TdT alone (somatic mutation)
      • late pro-B cells have downregulated TdT
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4
Q

When does a B-cell begin to express CD45R?

A
  • Progenitor B-cell stage (pro-B cell)
    • earliest stage of antigen-independent B-cell development
      • early pro-B cells express TdT alone (somatic mutation)
      • intermediate pro-B cells express both TdT and CD45R
      • late pro-B cells express CD45R and have downregulated TdT
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5
Q

How long do B-cells express CD45R?

A
  • pro-B cell development → throughout the remainder of B-cell ontogeny
    • CD45R = receptor for cell growth and differentiation
    • expressed on cell surface
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6
Q

Besides TdT and CD45R, what four other phenotypic markers are present during the pro-B cell stage?

A
  • Early
    • CD43 (leukosialin)
    • RAG-1 (recombination-activating gene)
    • RAG-2 (recombination-activating gene)
  • Late:
    • CD43 (leukosialin)
    • CD19 (BCR co-receptor)
    • CD40
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7
Q

What four phenotypic markers are downregulated as the late pro-B cells pass into the pre-B cell stage?

A
  • TdT
  • RAG-1
  • RAG-2
  • CD43
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8
Q

What are the two stages of a pre-B cell?

A
  • large mitotically active pre-B cells
    • successfully rearranged their Ig heavy chain genes
  • small non-dividing pre-B cells
    • begin to rearrange their Ig light chain genes
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9
Q

What cytokine do pre-B cells produce to stimulate division and differentiation?

A

IL-7

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10
Q

What two phenotypic markers are upregulated during the small pre-B cell phase as cells being to rearrange their Ig light chain genes?

A
  • RAG-1
  • RAG-2
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11
Q

What phenotypic marker becomes expressed during the large pre-B cell stage and is present throughout the remainder of B-cell ontogeny?

A

CD20

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12
Q

What is the final stage of B-cell development in the bone marrow?

A

immature B-cell

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13
Q

What do immature B-cells express?

A
  • Immature B-cells have successfully rearranged their light chain genes
    • express IgM
    • down regulate RAG-1 and RAG-2
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14
Q

What do immature B-cells begin to express as they develop into a mature B-cell and exit the bone marrow?

A

both IgM and IgD on their surface

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15
Q

What are the major cytokines required for B cell development?

A
  • IL-7
    • promotes B-cell lineage development
  • Blys (B-lymphocyte stimulator)
    • signaling through its receptor BR3
    • important for the survival of pre-immune B-cell stages from transition stage onwards
  • IL-4 + IL-3 + L-BCGF (low-molecular-weight B cell growth factor)
    • important in initiating the process of B-cell differentiation
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16
Q

What are TI-1 type antigens?

A
  • predominantly bacterial cell wall components
    • prototypical: lipopolysaccharide (LPS)
      • component of the cell wall of Gram-negative bacteria
17
Q

What are TI-2 type antigens?

A
  • predominantly large polysaccharide molecules with repeating antigenic determinants
    • e.g. Ficoll, dextran, polymeric bacterial flagellin, and poliomyelitis virus
18
Q

How does T-independent B cell activation occur with TI-1 type antigens?

A
  • B cell binds to LPS through either:
    • TLR4 = nonspecific (polyclonal activation)
    • BCR = specific (clonal activation)
  • Type 1 TI antigens can stimulate both immature and mature B cells through the use of TLR4.
19
Q

How does T-independent B cell activation occur with TI-2 type antigens?

A
  • B1 B-cells bind to Type TI antigens through the cross-linking of the BCR
    • BCR = specific (clonal activation)
  • Type 2 TI antigens can only stimulate mature B-cells through the use of the BCR
20
Q

What is the outcome of T-independent B cell activation with TI-1 type antigens?

A

ONLY IgM is produced in response to the stimulation.

21
Q

What is the outcome of T-independent B cell activation with TI-2 type antigens?

A

Mostly IgM is produced in response to this stimulation.

22
Q

What is the difference between polyclonal and clonal expansion?

A
  • Clonal
    • group of identical cells that share a common ancestry, meaning they are derived from the same cell.
  • Polyclonal
    • derived from many clones
23
Q

How does T-dependent B-cell activation occur?

A
  • Antigen recognized by BCR in the lymph node
    • endocytosis
    • presentation on MHC Class II peptide
  • Helper T-cell TCR recognizes antigen on B-cell MHC Class II peptide
    • CD40 on B-cell binds CD40L on T-cell
  • Helper T-cell releases cytokines - IL-2/IL-4/IL-5
    • recognized by B-cell Interleukin Receptor
    • push B-cell proliferation and differentiation
24
Q

What type of B cell is activated in T-dependent B-cell activation?

A

Follicular (B-2) B cells

25
Q

What is the outcome of T-dependent activation of B-cells?

A
  • B-cell class switching
  • Memory B-cell
  • Plasma Cell
    • IgM production
    • IgG production
26
Q

What are the steps of T-cell development in the bone marrow and thymus?

A
  • Marrow
    • Hematopoietic stem cell (HSC) → Hematopoietic precursor
      • migrates to thymic cortex
  • Thymic cortex
    • Early thymocyte development (CD4-CD8-)
      • T-cell precursor → DN1 (TCRß locus rearrangement, proliferation)
      • DN1 → DN2 (T-cell commitment)
      • DN2 → DN3 (ß-selection, proliferation)
      • DN3 → DN4 (TCR α locus rearrangement)
    • Positive selection
      • Double positive (DP) (CD4+CD8+) → one of the following:
        • CD8+ (single positive)
        • CD4+ (single positive)
        • Death by neglect
  • Thymic medulla
    • Negative selection
    • migration to blood
27
Q

At what stage in T cell development are c-kit (CD117), CD44, and CD25 expressed?

A
  • Stem cell
    • c-kit (CD117)+
  • Lymphoid progenitor
    • c-kit (CD117)+
  • DN1
    • c-kit (CD117)++, CD44+, CD25-
    • migrates from bone marrow → thymus
  • DN2​
    • c-kit (CD117)+++, CD44+, CD25+
    • subcapsular cortex
    • T-cell lineage commitment, ß chain rearrangement
  • DN3
    • c-kit(CD117)+, CD44-, CD25+, CD3
    • subcapsular cortex
    • expression of pre-TCR, ß selection
  • DN4
    • c-kit(CD117)low/-, CD44-, CD25-, CD3
    • subcapsular cortex → cortex
    • allelic exclusion of ß-chain
    • α-chain locus rearrangement begins
    • becomes DP thymocyte
28
Q

How does a double positive (DP) T-cell decide to become CD4+ or CD8+??

A
  • interacts with thymic epithelial cells
    • helps it decide (instructive model)
      • CD8 engagement signal
      • CD4 engagement signal
29
Q

What is the process of postive and negative selection of T-cells in the thymus?

A
  • DP thymocyte interacts with cortical thymic epithelial cells
  • Postive selection for DP Class I and/or Class II MHC molecules
    • 2-5% with low-intermediate affinity interaction are selected
  • Positively selected CD4+ and CD8+ cells migrate to medulla
  • Negative selection occurs
    • deletion of T-cells that have high affinity to self MHC or self antigen (autoreactive receptors)
30
Q

What is the process of activation of naïve CD4+ T cells into effector T cells?

A
  • Antigen recognition
    • NaÏve CD4+ T-cell binds APC via TCR signaling
  • Activation
    • co-stimulatory interaction between APC’s CD 80/86 and T-cells’ CD28
    • cytokine signaling: APC releases paracrine IL-2
  • Clonal Expansion
    • CD4+ IL-2R (CD25) binds IL-2
    • cell proliferates
    • CD4+ releases autocrine IL-2
  • Differentiation
    • Effector CD4+ T-cells produced
    • Memory CD4+ T-cells produced
31
Q

What is the process of activation of naïve CD8+ T cells into effector T cells?

A
  • Antigen recognition
    • NaÏve CD8+ T-cell binds APC via TCR signaling
  • Activation
    • co-stimulatory interaction between APC’s CD 80/86 and T-cells’ CD28
    • cytokine signaling: APC releases paracrine IL-2
  • Clonal Expansion
    • CD4+ IL-2R binds IL-2
    • cell proliferates
    • CD4+ releases autocrine IL-2
  • Differentiation
    • Effector CD8+ T-cells produced
    • Memory CD8+ T-cells produced
32
Q

What are the polarizing cytokines for Th1 differentiation?

A
  • IL-12
  • IL-18
  • IFN-gamma
33
Q

What are the polarizing cytokines for Th17 differentiation?

A
  • IL-1
  • IL-6
  • IL-23
  • TGF-beta
34
Q

What are the polarizing cytokines for Th2 differentiation?

A
  • IL-4
35
Q

What are the polarizing cytokines for Treg differentiation?

A
  • IL-2
  • TGF-beta
36
Q

What are the polarizing cytokines for Tfh differentiation?

A
  • IL-6
  • IL-21

IHO Week 4 - WLB (13 decks)

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