12. B cell activation and antibody production Flashcards
(73 cards)
1
Q
What activates B cells?
A
- BCR recognizing specific antigens
2. T helper cell sttimulate activation
2
Q
What are the effects of activating B cells?
A
- clones produce IgM or other isotypes
2. affinity maturation or memory cell formation
3
Q
What must an antigen bind to on Naive B cells in order to activate them?
A
- membrane IgM and IgD
4
Q
True/ False
B cell gives rise to as many as 5,000 antibody secreting cells per week.
A
True
5
Q
How many Abs are produced per day, at the peak of humoral response?
A
10^12
6
Q
When are IgM produced more frequently than IgG?
A
primary humoral response
7
Q
When will IgG, IgA, and IgE be produced in significantly higher amounts of in response to Ag?
A
secondary response
8
Q
What is able to induce primary humoral response?
A
all immunogens
9
Q
What produces a secondary humoral response?
A
mostly protein antigens
10
Q
Which humoral response has a higher affinity for Ab-Ag binding?
A
secondary, but is less variable
11
Q
What allows for a must faster and larger quantity of Abs to be produced?
A
- secondary response activates memory cells.
2. less time, and higher Abs secreted
12
Q
When will isotype switching be more common?
A
secondary response
13
Q
What has to happen for Ab to be able to initiate a response?
A
- Ag must be capture and transported to the B cell areas in lymphoid organs
14
Q
The majority of follicular B cells are what type of cells?
A
- naive B lymphocytes
2. AKA: recirculating B cells or B-2 cells
15
Q
Where do B-2 cells circulate to?
A
among secondary lymph organs. Spleen, and lymph nodes
16
Q
Where will follicular cells circulate to?
A
secondary lymph organs; spleen and LN
17
Q
Where will recirculating cells circulate to?
A
secondary lymph organs; spleen and LN
18
Q
Follicles are located in secondary lymph organs and are made of what?
A
follicular B cells that are attracted to CXCL13
19
Q
What do follicular dendritic cells secrete in order to migrate follicular B cells into follicles in the lymph nodes?
A
- CXCL13, which binds CXCR5(b cells)
20
Q
How does the Ag, that is presented to B cells, generally look at presentation?
A
- intact
- native conformation
- not processed by APC
21
Q
How are a majority of Ag transported to LN, especially if they are less than 70kDa?
A
- via afferent lymph vessels that drain into subcapsular sinus
22
Q
How are microbes and Ag-Ab complexes transported to the LN?
A
- undergo capture by subcapsular sinus macrophages
2. deliver Ag to follicles
23
Q
How are soluble Ags presented to the LN?
A
- they enter through afferent lymph vessels
2. migrate to B cell zone and interact directly with Ag-specific B cells
24
Q
How are large Ags transported to the LN?
A
- captured by resident DC.
- transported to follicles
- activate B cells
25
Ags that are in immune complexes, especially in the blood, migrate where?
1. migrate to spleen
| 2. interact with CR2 receptors of marginal zone B cells
26
What do marginal zone B cells that interact with complement coated Ags do with the immune complex after it binds to the B cell?
1. transfer the complex to follicular B cells
27
Blood-borne pathogens are captured by what cell, that transports them to marginal zone B cells?
plasmacytoid DC
28
What role do plasmacytoid DC have with immune response?
1. capture blood-borne pathogens and transport the pathogen to marginal zone B cells
29
What cells and where are polysaccharide Ags captured?
1. captured by tissue macrophages in the marginal zone of splenic lymphoid follicles
2. transferred to B cells in local area
30
How is a T-dependent Ab response generated?
1. follicular DC respond to protein Ags
31
How is a T-independent Ab response generated?
1. multivalent Ags activate marginal zone B cells in spleen and/or B-1 cells in mucous sites
32
Where are B-2 cells found and what are some features?
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
Where are B-1 cells mostly found?
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
What cells facilitate the formation of germinal centers?
follicular T helper cell
35
What occurs in the germinal centers?
B cell porliferation/differentiation
36
What are multivalent non-protein Ag, and what response is generated?
1. repeating epitopes (polysaccharides, lipids, nucleic acids)
2. T-independent response generated
37
What response is activated by BCR activity along with other costimulators as well?
T-independent response
38
The BCR and BAFF receptors produce what for B cells?
1. survival signals for follicular B cells
39
What is BAFF?
1. cytokine produced by myeloid cells in lymph and bone marrow
2. produces maturation/survival signal via BAFF receptor
40
What happens to protein Ags that are recognized by membrane Ig?
1. endocytosis/ processing
2. peptide fragment displayed to MHC II molecules
3. Th cells recognize and stimulate Ag specific B cells
41
What happens to hapten-carrier conjugates in order to generate an immune response?
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
What components are required for a T helper cell to activate a B cell?
1. interaction of CD40(b cell)/ CD40L(T cell)
| 2. interaction causes cytokine release to improve activation of B cells
43
What are the steps of T cell-dependent immune Response?
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
What are the events that B cells undergo in the germinal center?
1. somatic mutation
2. affinity maturation
3. isotype switching
4. memory B cell generation
5. long-lived plasma cells
45
Which B cell transcription factor is secreted extrafollicularly?
Blimp-1
46
What B cell transcription factor is secreted in germinal center?
Bcl-6
47
Where is a high and low rate of somatic hypermutation?
1. high rate: germinal center
| 2. low rate: extrafollicular
48
Which B cells have high affinity for Ag?
germinal center after undergoing affinity maturation
49
Where are follicular or germinal centers located?
secondary follicles
50
Where do extrafollicular cells localize at?
medullary cord on LN and between T cell zone and red pulp of spleen
51
What is the life-span of short-lived plasma cells and where are they formed from?
1. from extrfollicular with 3 day span
52
What sequence of steps must occur in order to generate follicular T helper cells?
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
What is IL-21?
1. cytokine secreted by Tfh for germinal center development and plasma cell generation
54
What functions does IL-21 perform?
1. plasma cell formation
| 2. germinal center development
55
What cytokines do Tfh secrete?
1. IFN-gamma---> IgG
2. IL-4--> IgE
- both control isotype switching
56
When are Tfh cell induction?
1. 4-7 days after Ag presentation
| 2. activated T cells are selected for induction
57
What signaling molecules draws Tfh cells into the GC and help with formation and function?
1. CXCL13
58
Are Tfh cells uniqeuly different then Th1, Th2, Th17 cells?
yes
59
What are the receptors/ligands, CD40, ICOS, IL-21, used for?
activation and differentiation of B cells
60
What occurs in the extrafollicular site of teh germinal center?
1. B cell activation and migration to the GC
61
What processes occur in the dark zone of the GC?
1. proliferation
2. isotype switching
3. somatic hypermutation of Ig V genes
62
What processes occur in the light zone of the GC?
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
What processes occur after leaving the light zone of the GC?
1. long-lived plasma cells migrate to bone marrow
| 2. memory cells enter recirculating lymphocyte pool
64
The dark zone of a GC can be stained with what stain to appear red, showing cycling cells?
anti-Ki67 stain
65
The light zone can be stained with what stain with high affinity for follicular DC?
anti-CD23 (green)
66
What are the outcomes of activating B cells?
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
What will help lead to Tfh cell development, and will block the differentiation into Th1, Th2, Th17?
high level of Bcl-6 expression in combination with decreased IL-2R expression
68
Heavy chain isotype switching to IgA requires what signals?
TGF-beta
APRIL
BAFF
69
What is the final result of switch recombination?
The two switch regions deleted, rearranged V region adjacent to new constant region
70
What is the process of switch recombination?
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
How are antigens, bound with complement factors delivered to B cell?
binding at CR2 of marginal zone cells that are activated and then transfer the Ag to follicular B cells
72
What is Bcl-6 and how is it activated?
1. activated via CD40/CD40L
2. represses cell p53, preventing cell cycle arrest and apoptosis
- - repressor that promotes GC survival
73
What is Blimp-1?
1. transcription gene regulator
| 2. causes reduced maintenance of mature B cells, increasing the proliferation/differentiation of naive B cells
