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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
what is marginal zone B cells role
caoture and respond to bloodborne antigens
26
B cell activation ; T dependant responses
-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
27
how does the B2 B cell induction signals work?
there are two signals
28
what is the first signal for B2 B cell induction
-the myltivalent protein antigen binds and crosslinks membrane ig receptor -b cell receptor delivers the first signal to the B cell
29
what is the second signal for B2 B cell induction
-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
30
in thje absence if T cells, antigen activated B cells are....
deleted or anergized
31
T cell drives B cell////
expansion, SHM, affinity maturation , isotope switching and memory
32
Prevnar vaccine; is for?
kids who don't mount response to s.pneumonia
33
how does the prevnar vaccine work
-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
where do the T and B cells meet?
-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
true or false: follicular dcs can bind lots of antigens
true
36
how do antigen activated T ceks proliferate and differentiate and antigen activated B cells move through the boundary region
they move closer ti each other through chemokine gradients
37
what is the TF of follicular helper T cells
BCL6
38
what are the cytokines that Tfh secrete
IL-21 and IL-4
39
which cytokine is important for the differentiation and activation of Tfh
IL-6 is important for their differentiation and activation
40
which ligand is also important for Tfh cells differentiation
ICOS
41
after the first wave of differentiation, B and T cell will....
migrate and form the germinal center
42
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
true
43
in the germinal center, B and T cells will go through ...
several rounds of activation
44
where will the B cells that were activated by the antigen in the light zone of the germinal center will go?
they will migrate top the dark zone and intensely proliferate
45
true or false: thhe dark zone is highly dense with t cells
false it is with B cells
46
after the B cells went to the dark zone, where will they go
to the light zone and test the B cell receptor by testing it with different antigens
47
why is the germinal center so important
it is the site of affinity maturation
48
in the dark zone, B cells undergo the process of....
somatic hypermutation
49
the first antibody diversification happens where?
in the bone marrow where the primary repertoire is generated due to VDJ recombination
50
when can the two further antibody diversification events happen
in the germinal center after antigen exposure
51
name the last twp antibody diversification events
-somatic hypermutation -classic switch recombination
52
what happens during somatic hypermutation
-induction of mutations in variable regions or rearranged Ig genes -this increases antibody affinity
53
what happens after B cells go through somatic hypermutation
The B cells exit and bind to an antigen on follicular analytic cells to test if the affinity of the receptor is good
54
what happens during class switch recombination
-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
what is dictated by the cytogenic environment
class switch recombination ex: strong TH1 response promotes switching to IgG
56
what happens if the immunoglobu;lin has low affinity with the antigen?
-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
what happens if the B cell is not properly selected
it will die of apoptosis
58
when does self reactivity happens
-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
if the immunoglobulin is high affinity then....
the B cell will receive help from the Tfh cell, it will survive and divide and differentiate into plasma cells
60
what is the difference between T cell dependant and independent affinity maturation
only with the T cell dependant you can get memory B cells
61
T cell independant responses: responds to thymus independent antigens; fall into 2 types:
-type 1 -type 2
62
type 1 t cell independant response; when type 1 antigens are at high concentration
-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
type 1 t cell independant response; when type 1 antigens are at low concentrations
-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
type 2 t cell independant response;
-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
what happens when you cross link Ig receptors to B cells
-this activates many B cell receptors and is sufficient for inducing activation of B cells
66
are the antibodies produced in type 2 independent response
no but they do their job but they are the first on the line and are short lived
67
why is T cell independant response kinda sucky
-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
how do t cell independant response leads to B1/MZ B cells?
-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
what are the defects in B cell genes can lead to major syndrome and pathologies
-cd40 -icos -aig enzyme -baffr -cvid -IgAD
70
what does the aig enzyme do
amylase enzyme involved is required for somatic hypermutation and class switching
71
what does Baffr do ?
involved in activation of T cell independant response
72
what happens if cvid and IgAD get fucked up
-can't class switch -more susceptible to disease and more chances of autoimmune disease
73
which deficience can augmentate your chances of getting celiacs disease and ibs
-IgA deficient T cell dependent or independent antibody responses in context of gut immunity at homeostasis
74
which deficience of antibodies in the gut
IgA deficient in independent t cell response
75
for which microbe, there needs to be a more specific response with t cells
SFB AND MUCISPIRILLUM
76
what did they find when they compared severe vs mild covid symptoms
-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
what would be the difference between antibodies made from cells in germinal center vs ones not made there
-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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