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Zach- Immunology > 12. B cell activation and antibody production > Flashcards

12. B cell activation and antibody production Flashcards

1
Q

What activates B cells?

A
  1. BCR recognizing specific antigens

2. T helper cell sttimulate activation

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2
Q

What are the effects of activating B cells?

A
  1. clones produce IgM or other isotypes

2. affinity maturation or memory cell formation

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3
Q

What must an antigen bind to on Naive B cells in order to activate them?

A
  1. membrane IgM and IgD
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4
Q

True/ False

B cell gives rise to as many as 5,000 antibody secreting cells per week.

A

True

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5
Q

How many Abs are produced per day, at the peak of humoral response?

A

10^12

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6
Q

When are IgM produced more frequently than IgG?

A

primary humoral response

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7
Q

When will IgG, IgA, and IgE be produced in significantly higher amounts of in response to Ag?

A

secondary response

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8
Q

What is able to induce primary humoral response?

A

all immunogens

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9
Q

What produces a secondary humoral response?

A

mostly protein antigens

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10
Q

Which humoral response has a higher affinity for Ab-Ag binding?

A

secondary, but is less variable

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11
Q

What allows for a must faster and larger quantity of Abs to be produced?

A
  1. secondary response activates memory cells.

2. less time, and higher Abs secreted

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12
Q

When will isotype switching be more common?

A

secondary response

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13
Q

What has to happen for Ab to be able to initiate a response?

A
  1. Ag must be capture and transported to the B cell areas in lymphoid organs
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14
Q

The majority of follicular B cells are what type of cells?

A
  1. naive B lymphocytes

2. AKA: recirculating B cells or B-2 cells

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15
Q

Where do B-2 cells circulate to?

A

among secondary lymph organs. Spleen, and lymph nodes

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16
Q

Where will follicular cells circulate to?

A

secondary lymph organs; spleen and LN

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17
Q

Where will recirculating cells circulate to?

A

secondary lymph organs; spleen and LN

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18
Q

Follicles are located in secondary lymph organs and are made of what?

A

follicular B cells that are attracted to CXCL13

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19
Q

What do follicular dendritic cells secrete in order to migrate follicular B cells into follicles in the lymph nodes?

A
  1. CXCL13, which binds CXCR5(b cells)
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20
Q

How does the Ag, that is presented to B cells, generally look at presentation?

A
  1. intact
  2. native conformation
  3. not processed by APC
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21
Q

How are a majority of Ag transported to LN, especially if they are less than 70kDa?

A
  1. via afferent lymph vessels that drain into subcapsular sinus
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22
Q

How are microbes and Ag-Ab complexes transported to the LN?

A
  1. undergo capture by subcapsular sinus macrophages

2. deliver Ag to follicles

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23
Q

How are soluble Ags presented to the LN?

A
  1. they enter through afferent lymph vessels

2. migrate to B cell zone and interact directly with Ag-specific B cells

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24
Q

How are large Ags transported to the LN?

A
  1. captured by resident DC.
  2. transported to follicles
  3. activate B cells
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25
Q

Ags that are in immune complexes, especially in the blood, migrate where?

A
  1. migrate to spleen

2. interact with CR2 receptors of marginal zone B cells

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26
Q

What do marginal zone B cells that interact with complement coated Ags do with the immune complex after it binds to the B cell?

A
  1. transfer the complex to follicular B cells
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27
Q

Blood-borne pathogens are captured by what cell, that transports them to marginal zone B cells?

A

plasmacytoid DC

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28
Q

What role do plasmacytoid DC have with immune response?

A
  1. capture blood-borne pathogens and transport the pathogen to marginal zone B cells
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29
Q

What cells and where are polysaccharide Ags captured?

A
  1. captured by tissue macrophages in the marginal zone of splenic lymphoid follicles
  2. transferred to B cells in local area
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30
Q

How is a T-dependent Ab response generated?

A
  1. follicular DC respond to protein Ags
31
Q

How is a T-independent Ab response generated?

A
  1. multivalent Ags activate marginal zone B cells in spleen and/or B-1 cells in mucous sites
32
Q

Where are B-2 cells found and what are some features?

A
  1. widespread
  2. high diversity
  3. memory
  4. target proteins
  5. normal isotype swithing
  6. always require T cell help
  7. continuously replaced
  8. IgD>IgM
33
Q

Where are B-1 cells mostly found?

A
  1. respiratory/GI tract
  2. low diversity
  3. low memory
  4. target carbohydrates
  5. IgM>IgD
  6. limited isotype switching
  7. rarely need T cell help
  8. self-renewing periphery
34
Q

What cells facilitate the formation of germinal centers?

A

follicular T helper cell

35
Q

What occurs in the germinal centers?

A

B cell porliferation/differentiation

36
Q

What are multivalent non-protein Ag, and what response is generated?

A
  1. repeating epitopes (polysaccharides, lipids, nucleic acids)
  2. T-independent response generated
37
Q

What response is activated by BCR activity along with other costimulators as well?

A

T-independent response

38
Q

The BCR and BAFF receptors produce what for B cells?

A
  1. survival signals for follicular B cells
39
Q

What is BAFF?

A
  1. cytokine produced by myeloid cells in lymph and bone marrow
  2. produces maturation/survival signal via BAFF receptor
40
Q

What happens to protein Ags that are recognized by membrane Ig?

A
  1. endocytosis/ processing
  2. peptide fragment displayed to MHC II molecules
  3. Th cells recognize and stimulate Ag specific B cells
41
Q

What happens to hapten-carrier conjugates in order to generate an immune response?

A
  1. hapten recognized by B cell
  2. conjugate is endocytosed
  3. carrier protein is processed in B cell; peptides are presented to Th cell
42
Q

What components are required for a T helper cell to activate a B cell?

A
  1. interaction of CD40(b cell)/ CD40L(T cell)

2. interaction causes cytokine release to improve activation of B cells

43
Q

What are the steps of T cell-dependent immune Response?

A
  1. B cell and CD4+ cells recognize Ags
  2. activated lymph migrate to each other, and interact
  3. interaction proliferates/differentiates B cells
  4. isotype switching and short-lived plasma cell generation extrafollicularly
  5. induction of follicular T helper cell
  6. events of germinal center occur to B cell
44
Q

What are the events that B cells undergo in the germinal center?

A
  1. somatic mutation
  2. affinity maturation
  3. isotype switching
  4. memory B cell generation
  5. long-lived plasma cells
45
Q

Which B cell transcription factor is secreted extrafollicularly?

A

Blimp-1

46
Q

What B cell transcription factor is secreted in germinal center?

A

Bcl-6

47
Q

Where is a high and low rate of somatic hypermutation?

A
  1. high rate: germinal center

2. low rate: extrafollicular

48
Q

Which B cells have high affinity for Ag?

A

germinal center after undergoing affinity maturation

49
Q

Where are follicular or germinal centers located?

A

secondary follicles

50
Q

Where do extrafollicular cells localize at?

A

medullary cord on LN and between T cell zone and red pulp of spleen

51
Q

What is the life-span of short-lived plasma cells and where are they formed from?

A
  1. from extrfollicular with 3 day span
52
Q

What sequence of steps must occur in order to generate follicular T helper cells?

A
  1. dendritic cell must activate T cell
  2. T cell interact with B cell (activating T cell)
  3. follicular T helper cells formed
  4. Tfh migrates to GC and interact with follicular dendritic cell
53
Q

What is IL-21?

A
  1. cytokine secreted by Tfh for germinal center development and plasma cell generation
54
Q

What functions does IL-21 perform?

A
  1. plasma cell formation

2. germinal center development

55
Q

What cytokines do Tfh secrete?

A
  1. IFN-gamma—> IgG
  2. IL-4–> IgE
    - both control isotype switching
56
Q

When are Tfh cell induction?

A
  1. 4-7 days after Ag presentation

2. activated T cells are selected for induction

57
Q

What signaling molecules draws Tfh cells into the GC and help with formation and function?

A
  1. CXCL13
58
Q

Are Tfh cells uniqeuly different then Th1, Th2, Th17 cells?

A

yes

59
Q

What are the receptors/ligands, CD40, ICOS, IL-21, used for?

A

activation and differentiation of B cells

60
Q

What occurs in the extrafollicular site of teh germinal center?

A
  1. B cell activation and migration to the GC
61
Q

What processes occur in the dark zone of the GC?

A
  1. proliferation
  2. isotype switching
  3. somatic hypermutation of Ig V genes
62
Q

What processes occur in the light zone of the GC?

A
  1. interaction of follicular DC with Ag and Tfh cells
  2. positive selection of high-affinity Ig receptors
  3. differentiation to memory or Ab secreting cells
63
Q

What processes occur after leaving the light zone of the GC?

A
  1. long-lived plasma cells migrate to bone marrow

2. memory cells enter recirculating lymphocyte pool

64
Q

The dark zone of a GC can be stained with what stain to appear red, showing cycling cells?

A

anti-Ki67 stain

65
Q

The light zone can be stained with what stain with high affinity for follicular DC?

A

anti-CD23 (green)

66
Q

What are the outcomes of activating B cells?

A
  1. increase survival/proliferation
  2. increase interaction with Th cells
  3. increase responsiveness to cytokines
  4. express CCR7 to migrate from follicle area to T cell area.
67
Q

What will help lead to Tfh cell development, and will block the differentiation into Th1, Th2, Th17?

A

high level of Bcl-6 expression in combination with decreased IL-2R expression

68
Q

Heavy chain isotype switching to IgA requires what signals?

A

TGF-beta
APRIL
BAFF

69
Q

What is the final result of switch recombination?

A

The two switch regions deleted, rearranged V region adjacent to new constant region

70
Q

What is the process of switch recombination?

A
  1. Ig heavy chain recombined in VDJ exon for new sequence
  2. CD40 driven to change promoter switch regions
  3. Regions rich in GC sequence. Allows AID (activation-induced deaminase) to convert C to U. generates a loop to free a ssDNA. All C are converted to G, the U are removed, and double stranded nicks are placed to allow for switch regions removal
  4. Two switch regions deleted, rearranged V region adjacent to new constant region
71
Q

How are antigens, bound with complement factors delivered to B cell?

A

binding at CR2 of marginal zone cells that are activated and then transfer the Ag to follicular B cells

72
Q

What is Bcl-6 and how is it activated?

A
  1. activated via CD40/CD40L
  2. represses cell p53, preventing cell cycle arrest and apoptosis
    - - repressor that promotes GC survival
73
Q

What is Blimp-1?

A
  1. transcription gene regulator

2. causes reduced maintenance of mature B cells, increasing the proliferation/differentiation of naive B cells

Zach- Immunology (10 decks)

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