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MIMM 314 > Abadie lecture 1 > Flashcards

Abadie lecture 1 Flashcards

1
Q

what are the 2 ways to classify b cells

A

-state of differentiation
-location between different secondary organs
this depends on b cell development

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2
Q

how long does it take for a b cell to develop from hematopoietic stem cells

A

a few weeks

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3
Q

where does the antigen independent phase happen in B cell dev

A

in the bone marrow

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4
Q

antigen independent phase for b cell dev

A

-it is the vdj recombination

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5
Q

what does vdj do?

A

-genetic recombination in heavy and light chains
-this changes the structure of variable regions in heavy and light chains causing a change in the affinity of variable region of an antibody

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6
Q

where is the pro b cell

A

in the bone marrow

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7
Q

The pro b cell starts with a…

A

pro bcr made of calnexin, igalpha and igbeta

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8
Q

true or false: bcrs have a lot of similarities with tcrs

A

true

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9
Q

how can bcr become antibodies

A

we cleave them

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10
Q

the pre b cell has a pre bcr with….

A

VpreB and Vdelta5 (surrogate light chains) and Igu

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11
Q

how can we know if a B cell is mature

A

it has a mature BCR

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12
Q

where does the antigen dependent phage happens in b cell dev

A

in secondary lymphoid organs

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13
Q

T1 B cell

A

tested for auto reactivity and eliminated by apoptosis

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14
Q

what is a T2B cell

A

gives rise to mature B cells

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15
Q

what is a T3 B cell

A

-develops from T2 B cells and mature B cells
-they express B220+, CD93+, IgMlow and CD23+

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16
Q

true or false: preplasma secrete antibodies

A

false: pre-plasma and plasma cells secrete antibodies

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17
Q

which cells have the ability to come back in the event of a second infection

A

memory B cells

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18
Q

what are the 2 b lymphocytes subsets aka mature B cells

A

B1 and B2 (follicular)

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19
Q

what are follicular B cells

A

-B2 cells
-t cell dependant B cell response
-most common B cell subset (90%)
-involved principally against protein antigens
-follicular comes from their location
-these are from precursors in the bone marrow

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20
Q

follecular B cells; come from their location: where?

A

-they locate into B cell follicle in spleen or other secondary lymphoid organs

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21
Q

what are B1 B cells

A

-t cell independant B cell response
-do not arise from the bone marrow
-first line of defense
-found in the gut , peritoneal and pleural cavities
-they have rapid productions of antibody such as Igm

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22
Q

where do B1 B cells arise

A

-fetal liver

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23
Q

marginal zome B cells

A

-t cell independant B cell response
-these are also classical B cells
-they are found in the marginal zone in the spleen which is the closest to the blood stream
-they represent a first line of defense against antigens in blood since they can respond rapidly
-long lived b cells and may be self renewing

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24
Q

why are marginal zone B cells T cell independent

A

they use DC and respond to the environment

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25
Q

what is marginal zone B cells role

A

caoture and respond to bloodborne antigens

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26
Q

B cell activation ; T dependant responses

A

-includes thymus dependent antigens such as proteins (this makes the B cells dependent upon helper T cells to induce antibody production)
-leads to B2 B cells

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27
Q

how does the B2 B cell induction signals work?

A

there are two signals

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28
Q

what is the first signal for B2 B cell induction

A

-the myltivalent protein antigen binds and crosslinks membrane ig receptor
-b cell receptor delivers the first signal to the B cell

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29
Q

what is the second signal for B2 B cell induction

A

-recognition of protein fragments by activated helper T cells
-activated T cell binds B cells through antigen receptor and via cd40L(T)/CD40(B) INTERACTION
-cytokines will also be delivered from the T cells in the form of IL-21
-b cell is then activated to divide and differentiate

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30
Q

in thje absence if T cells, antigen activated B cells are….

A

deleted or anergized

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31
Q

T cell drives B cell////

A

expansion, SHM, affinity maturation , isotope switching and memory

32
Q

Prevnar vaccine; is for?

A

kids who don’t mount response to s.pneumonia

33
Q

how does the prevnar vaccine work

A

-it promotes a t cell dependant response
-conjugated antigen of interest (polyribosyl ribitol phosphate) to a carrier that goes through the T cell dependant pathway (diphtheria toxiod)
-the B cell can then produce an antibody against the poly saccharide antigen on the surface of the bacterium

34
Q

where do the T and B cells meet?

A

-in secondary lymphoid organs
-naive B cell will search for specific antigens displayed by follicular dendritic cells in the primary follicle
-antigen activated T cells proliferate and differentiate and antigen activated B cells move to the boundary region
-antigen activated B cells present antigen to effector T follicular helper cells which form cognate interactions and cognate pairs

35
Q

true or false: follicular dcs can bind lots of antigens

A

true

36
Q

how do antigen activated T ceks proliferate and differentiate and antigen activated B cells move through the boundary region

A

they move closer ti each other through chemokine gradients

37
Q

what is the TF of follicular helper T cells

A

BCL6

38
Q

what are the cytokines that Tfh secrete

A

IL-21 and IL-4

39
Q

which cytokine is important for the differentiation and activation of Tfh

A

IL-6 is important for their differentiation and activation

40
Q

which ligand is also important for Tfh cells differentiation

A

ICOS

41
Q

after the first wave of differentiation, B and T cell will….

A

migrate and form the germinal center

42
Q

true or false: some B and T cells in the germinal center will leave and become short lived plasma cells to secrete antibodies for a short time

A

true

43
Q

in the germinal center, B and T cells will go through …

A

several rounds of activation

44
Q

where will the B cells that were activated by the antigen in the light zone of the germinal center will go?

A

they will migrate top the dark zone and intensely proliferate

45
Q

true or false: thhe dark zone is highly dense with t cells

A

false it is with B cells

46
Q

after the B cells went to the dark zone, where will they go

A

to the light zone and test the B cell receptor by testing it with different antigens

47
Q

why is the germinal center so important

A

it is the site of affinity maturation

48
Q

in the dark zone, B cells undergo the process of….

A

somatic hypermutation

49
Q

the first antibody diversification happens where?

A

in the bone marrow where the primary repertoire is generated due to VDJ recombination

50
Q

when can the two further antibody diversification events happen

A

in the germinal center after antigen exposure

51
Q

name the last twp antibody diversification events

A

-somatic hypermutation
-classic switch recombination

52
Q

what happens during somatic hypermutation

A

-induction of mutations in variable regions or rearranged Ig genes
-this increases antibody affinity

53
Q

what happens after B cells go through somatic hypermutation

A

The B cells exit and bind to an antigen on follicular analytic cells to test if the affinity of the receptor is good

54
Q

what happens during class switch recombination

A

-replacement of the constant region by another constant region aka gamma, epsilon or alpha
-switches the effector function of the antibody
-this happens at the level oof the switch regions : excision, recombination and replacement
-this leads to production of isotypes with the same antigenic specificity by different effector functions

55
Q

what is dictated by the cytogenic environment

A

class switch recombination
ex: strong TH1 response promotes switching to IgG

56
Q

what happens if the immunoglobu;lin has low affinity with the antigen?

A

-the B cell was not selected properly since the bcr is not cross linked and can’t properly resent its antigen to the Tfh cell

57
Q

what happens if the B cell is not properly selected

A

it will die of apoptosis

58
Q

when does self reactivity happens

A

-in the germinal center during affinity maturation
-it can accidently happen through the process and if the cells do not receive help from the Tfh cells, the self reactive cells will be eliminated

59
Q

if the immunoglobulin is high affinity then….

A

the B cell will receive help from the Tfh cell, it will survive and divide and differentiate into plasma cells

60
Q

what is the difference between T cell dependant and independent affinity maturation

A

only with the T cell dependant you can get memory B cells

61
Q

T cell independant responses: responds to thymus independent antigens; fall into 2 types:

A

-type 1
-type 2

62
Q

type 1 t cell independant response; when type 1 antigens are at high concentration

A

-this induces mitosis to most B cells because of binding to PRRs on B cell surfaces (mitogenic)
-this leads to polyclonal B cell activation and non-specific antibody response

63
Q

type 1 t cell independant response; when type 1 antigens are at low concentrations

A

-the antiogen only activates those B cells that bind the antigen through the Ig receptor
-since only a few B cells can bind, this leads to a more specific antibody response

64
Q

type 2 t cell independant response;

A

-highly repetitive surface structures such as flagelline or bacterial capsular polysaccharide; these antigens are more complex
-this is not mitogenic but can crosslink Ig receptors
-from this, there’s lots of IgM, no to little isotype switching no SHM and no memory

65
Q

what happens when you cross link Ig receptors to B cells

A

-this activates many B cell receptors and is sufficient for inducing activation of B cells

66
Q

are the antibodies produced in type 2 independent response

A

no but they do their job but they are the first on the line and are short lived

67
Q

why is T cell independant response kinda sucky

A

-when making vaccines for kids because they have many immature B and T cell independent response only happens in mature B cells
-especially for s pneumonia that has the pneumococcal capsular polysaccharide

68
Q

how do t cell independant response leads to B1/MZ B cells?

A

-b cells become activated after antigen binds to the bcr and the brc/antigen becomes internalized
-in the absence of the T cell, the second signal required for b cell activation is provided by the antigen itself that binds to innate immunity receptor like a tlr
-this allows the b cell to start proliferating

69
Q

what are the defects in B cell genes can lead to major syndrome and pathologies

A

-cd40
-icos
-aig enzyme
-baffr
-cvid
-IgAD

70
Q

what does the aig enzyme do

A

amylase enzyme involved is required for somatic hypermutation and class switching

71
Q

what does Baffr do ?

A

involved in activation of T cell independant response

72
Q

what happens if cvid and IgAD get fucked up

A

-can’t class switch
-more susceptible to disease and more chances of autoimmune disease

73
Q

which deficience can augmentate your chances of getting celiacs disease and ibs

A

-IgA deficient T cell dependent or independent antibody responses in context of gut immunity at homeostasis

74
Q

which deficience of antibodies in the gut

A

IgA deficient in independent t cell response

75
Q

for which microbe, there needs to be a more specific response with t cells

A

SFB AND MUCISPIRILLUM

76
Q

what did they find when they compared severe vs mild covid symptoms

A

-differences in the ways the B cell response is induced
-in severe infection, impared germinal center response
-in mild, there was a good germinal center response and a good extra follicular response

77
Q

what would be the difference between antibodies made from cells in germinal center vs ones not made there

A

-amount of hypersomatic hypermutation
-more of it if the cell spent more time in the germinal center

MIMM 314 (11 decks)

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