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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
Q

in addition to affinity maturation, what happens to Ig?

A

also undergo class-switching

26
Q

key role of germinal center

A

memory

27
Q

why is it important that we increase Ig affinity?

A

so Ab can respond to any antigen with sufficient affinity

28
Q

where and how do B cells first increase diversity?

A

in BM

there is random VDJ recombination in pre/pro/immature B cells before antigen is seen –> creates primary repertoire

29
Q

where and how (2) do B cells increase diversity after BM?

A

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
Q

what enzyme allows for affinity maturation in secondary lymphoid organs

A

Activation Induced Cytidine Deaminase (ACID)

31
Q

Why is there B cell negative selection?

A

B cells always re-testing ability of Ig to recognize antigen

32
Q

what happens if the affinity of Ig to antigen is NOT strong enough?

A

B cells will be deleted

33
Q

what happens if the affinity of Ig to antigen IS strong enough?

A

T cells will activate B cells and instruct them to enter germinal cell for further maturation

34
Q

what happens if there is a defect or deficiency in genes involved in B cell development and function?

A

can lead to severe primay immunodeficiency and inability to mount proper response

35
Q

what happens if a gene deficiency makes you unable to class switch?

A

cannot make specific Ab and only make IgM –> develop hyper-IgM syndrome and cannot fight infection

36
Q

does the gut have T-independent or T-dependent pathways

A

both

37
Q

why does the gut have immune response?

A

requires epithelium to prevent microbes from entering and must regulate microbiota

38
Q

what is the most important mechanism of immune defense in the gut?

A

IgA

39
Q

How does IgA allow for immune defense in the gut?

A

IgA forms dimer that can cross epithelium barrier and trigger immune exclusion

40
Q

what is immune exclusion?

A

IgA binds microbes and prevents them from penetrating and entering lamina propria

41
Q

what determines whether there is a T-dependent or T-independent response in the gut?

A

location!

42
Q

where does the T-dependent response occur in the gut?

A

in Peyer’s Patch

43
Q

what is a Peyer’s Patch?

A

secondary lymphoid organ located right below epithelium

44
Q

what occurs in Peyer’s Patch?

A

has germinal center and generation of Ab in T-dependent manner

45
Q

where does the T-independent response in the gut occur?

A

in lamina propria

46
Q

describe the T-independent response in the gut

A

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
Q

what is a good way of determining whether a pathogen triggers T-dependent or T-independent response?

A

give pathogen to control mice and mice without T cells –> compare the production of Ab in absence and presence of T cells

48
Q

which 2 pathogens allowed for production of Ab only when T cells are present?

A
  1. Mucispirillum
  2. SFB
49
Q

How can you determine if there are germinal center reactions occuring?

A

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
Q

what determines the B cell response in COVID?

A

the severity of the infection

51
Q

describe the production of B cells with SEVERE COVID

A

Impaired germinal center reaction –> plasma and memory B cells are made outside of the germinal center in the extra-follicular space

52
Q

describe the Ab with SEVERE COVID

A

Since B cells not produced in germinal center, they are lower affinity Ab

53
Q

describe the production of B cells with MILD COVID

A

Make germinal and non-germinal center plasma and memory cells

54
Q

when are B cells APC?

A

In germinal center to present antigen to Tfh

55
Q

3 main functions of B cells

A
  1. Ab production
  2. Ag presentation
  3. Cytokine production
56
Q

2 treatments for MS

A
  1. Anti-CD20
  2. TACI-Ig
57
Q

what does anti-CD20 do?

A

deplete B cells to prevent them from reaching the brain and creating inflammatory lesions –> helps disease!

58
Q

what does TACI-Ig do?

A

acts on plasma cells to reduce serum Ab titers (only affects circulating B cells) –> does NOT help disease!

59
Q

in general, why do anti-CD20 and TACI-Ig have different effects on disease severity

A

B cells have diff roles in diff contexts

60
Q

why does anti-CD20 treatment work?

A

Anti-CD20 removes B cells that make pro-inflammatory cytokine IL6 –> treatment prevents inflammation via blocking this cytokine

61
Q

why does TACI-Ig not work?

A

plasma cells produce inflammatory cytokines that are actually beneficial –> treatments prevents this benefit

MIMM 314 (23 decks)

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