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MIMM 314 > Lecture 14 (pt 2) > Flashcards

Lecture 14 (pt 2) Flashcards

1
Q

where do antigen-specific T and B cells meet?

A

in secondary lymphoid organs

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2
Q

where do naive B cells search for antigen?

A

in primary follicle

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3
Q

describe naive B cells searching for antigen

A

naive B cells in the primary follicle capture antigen displayed on follicular DC that displays a lot of antigens

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4
Q

how do B cells enter the secondary lymphoid organs?

A

via HEV

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5
Q

how do naive B cells capture antigen that directly enter the secondary lymphoid organs?

A

ex. viruses

pathogen enters in capsule and are captured by macrophages to be presented to B cells

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6
Q

what happens once B cells meet their antigen in the follicles?

A

B cells express CCR7 which lets them migrate to boundary region

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7
Q

what happens at the boundary region?

A

B cells meet T cells which have been activated by the same antigen –> B cells activate and make the FIRST WAVE of B cells that produce Ab

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8
Q

which B cells go thru the germinal center?

A

the FIRST WAVE of Ab-producing B cells don’t go thru the germinal center

then other cells go thru germinal center to make higher affinity Ab

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9
Q

where do T cells meet their antigen in the secondary lymphoid organ?

A

T cell zone

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10
Q

where are Tfh cells located?

A

in LN, spleen

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11
Q

what are Tfh required for?

A

Tfh are required for the germinal center reaction

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12
Q

what causes T cells to differentiate into Tfh?

A

lineage-determining TF called BCL6

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13
Q

Describe the activity of Tfh

A
  1. T cell meets antigen from DC
  2. T cell has BCL6 to make Tfh
  3. Tfh meets B cell
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14
Q

2 outcomes of Tfh interacting with B cell

A
  1. B cells that receive help from T cell and become Ab-producing cell
  2. B cells that migrate to germinal center
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15
Q

what ligand is important in the interaction btwn Tfh and B cell?

A

ICOS

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16
Q

What are 2 cytokines that are important for activating B cells?

A
  1. IL21
  2. IL4
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17
Q

What are the 2 waves of B cells?

A
  1. B cells that are short-lived and rapidly producing Ab
  2. B cells that migrate to germinal center with higher affinity and memory
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18
Q

what is the germinal center?

A

aggregation of T and B cells

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19
Q

where is the germinal center?

A

B cell follicle

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20
Q

2 zones of germinal center?

A

LIGHT

DARK

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21
Q

what happens in the light zone of the germinal center?

A

B cells capture antigen and interact with Tfh

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22
Q

what happens in the dark zone of the germinal center?

A

B cells leave the light zone and go to the dark zone –> B cells proliferate and increase Ig affinity

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23
Q

why is the dark zone called the dark zone?

A

very cell dense since B cells are proliferating

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24
Q

how does Ig increase its affinity

A

affinity maturation

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25
in addition to affinity maturation, what happens to Ig?
also undergo class-switching
26
key role of germinal center
memory
27
why is it important that we increase Ig affinity?
so Ab can respond to any antigen with sufficient affinity
28
where and how do B cells first increase diversity?
in BM there is random VDJ recombination in pre/pro/immature B cells before antigen is seen --> creates primary repertoire
29
where and how (2) do B cells increase diversity after BM?
in secondary lymphoid organs 1) SOMATIC HYPERMUTATION - mutations in variable region of Ig to increase binding affinity 2) CLASS SWITCH RECOMBINATION - diff genes for diff isotypes with switch regions to allow certain constant region
30
what enzyme allows for affinity maturation in secondary lymphoid organs
Activation Induced Cytidine Deaminase (ACID)
31
Why is there B cell negative selection?
B cells always re-testing ability of Ig to recognize antigen
32
what happens if the affinity of Ig to antigen is NOT strong enough?
B cells will be deleted
33
what happens if the affinity of Ig to antigen IS strong enough?
T cells will activate B cells and instruct them to enter germinal cell for further maturation
34
what happens if there is a defect or deficiency in genes involved in B cell development and function?
can lead to severe primay immunodeficiency and inability to mount proper response
35
what happens if a gene deficiency makes you unable to class switch?
cannot make specific Ab and only make IgM --> develop hyper-IgM syndrome and cannot fight infection
36
does the gut have T-independent or T-dependent pathways
both
37
why does the gut have immune response?
requires epithelium to prevent microbes from entering and must regulate microbiota
38
what is the most important mechanism of immune defense in the gut?
IgA
39
How does IgA allow for immune defense in the gut?
IgA forms dimer that can cross epithelium barrier and trigger immune exclusion
40
what is immune exclusion?
IgA binds microbes and prevents them from penetrating and entering lamina propria
41
what determines whether there is a T-dependent or T-independent response in the gut?
location!
42
where does the T-dependent response occur in the gut?
in Peyer's Patch
43
what is a Peyer's Patch?
secondary lymphoid organ located right below epithelium
44
what occurs in Peyer's Patch?
has germinal center and generation of Ab in T-dependent manner
45
where does the T-independent response in the gut occur?
in lamina propria
46
describe the T-independent response in the gut
DCs produce mediators like BAFF and APRIL that are recognized by the TACI receptor on B cell this signal is sufficient to promote differentiation of IgA-producing plasma cells in the gut
47
what is a good way of determining whether a pathogen triggers T-dependent or T-independent response?
give pathogen to control mice and mice without T cells --> compare the production of Ab in absence and presence of T cells
48
which 2 pathogens allowed for production of Ab only when T cells are present?
1. Mucispirillum 2. SFB
49
How can you determine if there are germinal center reactions occuring?
Day 0 - cells have fluorescence of 1 colour Day 7 - lots of colours with differentiation Day 14 - just 1 colour proliferates via clonal expansion
50
what determines the B cell response in COVID?
the severity of the infection
51
describe the production of B cells with SEVERE COVID
Impaired germinal center reaction --> plasma and memory B cells are made outside of the germinal center in the extra-follicular space
52
describe the Ab with SEVERE COVID
Since B cells not produced in germinal center, they are lower affinity Ab
53
describe the production of B cells with MILD COVID
Make germinal and non-germinal center plasma and memory cells
54
when are B cells APC?
In germinal center to present antigen to Tfh
55
3 main functions of B cells
1. Ab production 2. Ag presentation 3. Cytokine production
56
2 treatments for MS
1. Anti-CD20 2. TACI-Ig
57
what does anti-CD20 do?
deplete B cells to prevent them from reaching the brain and creating inflammatory lesions --> helps disease!
58
what does TACI-Ig do?
acts on plasma cells to reduce serum Ab titers (only affects circulating B cells) --> does NOT help disease!
59
in general, why do anti-CD20 and TACI-Ig have different effects on disease severity
B cells have diff roles in diff contexts
60
why does anti-CD20 treatment work?
Anti-CD20 removes B cells that make pro-inflammatory cytokine IL6 --> treatment prevents inflammation via blocking this cytokine
61
why does TACI-Ig not work?
plasma cells produce inflammatory cytokines that are actually beneficial --> treatments prevents this benefit

MIMM 314 (23 decks)

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