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IHL Exam 2 > B cell activation (bowden 9/5) > Flashcards

B cell activation (bowden 9/5) Flashcards

1
Q

Clonal selection

A

The process of gene rearrangement of the heavy and light chains and the combinatorial association of these chains occurs during B cell development and is independent of antigen.

antigen simply selects those clones which have the appropriate receptor

the selected clones are then activated, proliferate, and differentiate into antibody secreting plasma cells

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2
Q

IL-3

A

acts on immature progenitors

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3
Q

CD20 and CD19

A

on surface of mature B cell

these are pan B cell markers

if you do an analysis of someones lymphocytes in their blood, use antibodies against CD20 or CD19 to look for those

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4
Q

Mature naive B cells exit marrow and enter what?

A

secondary lymphoid organs…

Lymph nodes and spleen

enter via HEV

if not activated by antigen they die

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5
Q

what do B cells that develop from fetal liver-derived stem cells differentiate into?

A

B-1 cells

these response to non-protein Ag in the mucosa

found in GALT/MALT/BALT

have an extra marker on their surface (CD5+)

make predominantly shortlived IgM responses

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6
Q

what do B cells that develop from BM progenitors after birth differentiate into?

A

B-2

Two subsets of B-2 include:
Follicular B cells
Marginal B cells

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7
Q

Follicular B cells

A

of the B-2 subset

re-circulating B cells (Majority)

give rise to long-lived plasma cells (IgG, IgE, IgA)

see protein antigens and require helper T cells

spleen and other lymphoid organs

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8
Q

Marginal B cells

A

of the B-2 subset

reside in the spleen DON”T recirculate

respond to blood-borne polysaccharide antigens

make predominantly IgM

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9
Q

Membrane bound Ig does not have…

A

cytoplasmic tail… so it cannot signal

all of signalling from binding of mIg comes from the Ig-alpha and Ig-beta and B cell co-receptors.

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10
Q

Antigen dependent phase

A

Response initiated by recognition of antigen (its epitope) by B cell specific for that antigen (idiotope)

Antigens binds to membrane Ig on naive cells and activates these cells

activation can be T dependent or T independent

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11
Q

T cell dependent

A

some T cells stimulate, or help, B lymphocytes to produce antibodies

In the absence of T cell help, protein antigens elicit weak or no antibody responses

Protein antigens are processed in antigen-presenting cells (APCs) and recognized by helper T lymphocytes, which play an important role in B cell activation and induce heavy-chain isotype switching and affinity maturation.

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12
Q

T independent

A

Polysaccharides, lipids, and other nonprotein antigens stimulate antibody production without the involvement of helper T cells

The antibodies produced in response to T-independent antigens show relatively little heavy-chain isotype switching and affinity maturation.

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13
Q

Naive B cells in circulation

A

Travel through secondary lymphoid tissue

enter from blood if going to spleen

in lymph if going into nodes

migrate to primary lymphoid follicles which contain FDC’s

enter through HEV

if they don’t encounter antigen they migrate to primary follicle

receive signal to survive from FDC’s

exit through efferent lymphatic vessels

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14
Q

competition of B cells for survival signals

A

too many B cells, not enough FDC’s to provide signals for survival

naive b cells die within weeks in absence of antigen

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15
Q

L selectin

A

expressed on naive b cells

binds to peripheral node addresin (PNAd)

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16
Q

what does CCR7 bind and where is it expressed

A

expressed on Naive B cells

binds to CXCL19 or CXCL21 on lymph node HEV’s

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17
Q

What do naive b cells express

A

L selectin

CCR7

LFA1

CXCR4

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18
Q

what does LFA1 bind?

A

ICAM-1 on lymph node HEV’s

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19
Q

what does CXCR4 bind to ?

A

CXC12 on lymph node HEV’s

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20
Q

B cell homing

A

Cytokines produced by HEV and stromal cells activates integrins

B cell migrates to follicular zone by CXCL13

Dendritic cells migrate in from periphery and bring in antigen (attracted to CCL21)

Dendritc cells secrete CCL18 and CCL19 which attract T cells to the lymph node

B cells respond to CXCL19 and once in the lymph node they migrate to where the FDC’s are secreting CXCL13

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21
Q

CXCL13

A

Mediates follicle migration

is secreted by Follicular dendritic cells (FDC’s) in the lymph node which attracts more B cells

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22
Q

B cell activation first signal (one type)

A

Ag recognition by membrane bound Ig’s

Must crosslink 2 or more BCR

Signaling occurs through Igalpha and Igbeta cytoplasmic tails

prepares cell for interaction with 2nd signal

at this point it is minimally activated

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23
Q

B cell activation first signal (with complement)

A

Ag bound with C3d

C3d binds CR2 (the BCR co-receptor complex)

signaling occurs through the Igalpha and Igbeta, CR2 and CD19 cytoplasmic tails

prepares cell for second signal

you do not need cross linking for signaling of two or more Ig’s if CD3 is involved ***

100 fold more immunogenic

24
Q

what is the BCR co-receptor complex

A

CR2 and CD19

25
after B cells are activated they upregulate and downregulate what?
upregulate CCR7 | downregulate CXCR5
26
after T cells are activated they upregulate and downregulate what?
downregulate CCR7 upregulate CXCR5 done in order to migrate to
27
CCL21
secreted by HEV and stromal cells
28
what expresses a receptor for CCL21
Dendritic cells when it binds to CCL21 it migrates into the lymph node
29
CCL18 and CCL19
secreted by Dendritic cells attracts T and B cells to developing lymph node
30
Second signal
Stimulation of b cells by antigen induces expression of B7 this allows for interaction with CD28 on Th cells Th cells are now activated and can perform effector function of providing cytokine help to B cells T activation causes expression of CD40L that interacts with CD40 on B cells The interaction of CD40 with ligand on the T cell is the second signal that causes activation and B cell differentiation
31
what is B7 expressed on and what does it bind?
B cells binds CD28
32
what is CD28 expressed on?
T cells constitutively expressed
33
CD40L
expressed on T cells after T cells are activated due to the interaction of CD28/B7
34
How does activation of B and T cells maintain specificity of the immune response?
B/c the expression of B7 and CD40L are dependent on antigen stimulation, only lymphocytes specifically interacting with antigen (lymphocytes specific for that antigen epitope) are activated
35
CD40
constitutively active on B cells
36
Function of cytokines released by Th cells
Class switching Augment B cells differentiation and proliferation (Clonal expansion)
37
IL-4
promotes class switching to IgE
38
IFN-gamma
induces switch to IgG2a
39
TGF-beta and IL-5
lead to switch to IgA
40
Switch recombination in cross switching
occurs in germinal center CD40/CD40L and cytokines trigger isotype switching Rearranged VDJ gene segment on heavy chain recombines with a downstream C region gene (not being used) Class switching does not change the specificity of an antibody molecule, only its isotope and therefore potentially its biological function
41
AID
activation-induced deaminase key enzyme in class switching expressed by CD40 signals
42
Somatic Hypermutation: Affinity Maturation
Introduction of point mutations in the Variable regions of Ig genes, resulting in an expansion of the antibody repertoire to generate high-affinity antigen-specifc antibodies =hypermutation AID converts Cs to Us after somatic hypermutation occurs B cells still have to be selected by FDC's takes place in the germinal center often occurs simultaneously with class switching
43
after somatic hypermutation, what is the fate of B cells...
only B cells with high affinity antigen receptors encounter antigen on the FDC's and present antigen to T fh cells these are the B cells that survive
44
Plasma cells
Terminally differentiated Ab secreting B cell surface markers CD27 loses CD19 and CD20 surface markers
45
Memory cells
survive for long periods of time without additional Ag stimulation capable of mounting a rapid response to subsequent exposure responsible for secondary immune response
46
why don't IgM's undergo affinity maturation...
b/c you always are expressing IgM and if you don't have the CD40 L CD40 interaction you don't get class switching and you also don't get somatic hypermutaiton of IgM no signals from helper T cells --> no switching CD40: CD40L required for isotype switching: T dependent antigen only
47
Memory cells are only induced by...
protein antigens b/c in order to go through isotype switching and somatic hypermuation you need T cell help, which t-dependent antigens require... so.... no memory cells are created for t-independent antigens b/c they don't lead to these final steps
48
Primary response is induced by?
all immunogens
49
Secondary response is induced by
only protein antigens
50
T-dependent antigens
soluble proteins can do isotype switching can do affinity maturation (somatic hypermutation) can have immunological memory No polyclonal activation
51
T independent antigens
Chemical nature: - bacterial cell-wall components (LPS) - capsular polysaccharides - polymeric protein antigens usually no isotype switching no affinity maturation no immunologic memory no polyclonal activation
52
Control mechanism/Antibody feedback
secreted antibody binds to antigen, forms Ag/Ig complex Antigen/antibody complex binds to B cell IgG and Fc receptor causes a block in b cell receptor signaling
53
Natural antibodies
IgM only Produced by B-1 (sit in the mucosa) and mariginal zone b cells specific for bacteria in the area cross react with blood anlloantigens
54
Primary response
time lag after immunization/infection 5-10 days smaller antibody production antibody istotype IgM>IgG Antibody affinity is lower, more variable relatively high doses of antigens for required immunizations
55
Secondary response
time lag after immunization/infection 1-3 days larger peak response (antibody production) relative increase in IgG and IgA or IgE higher average affinity only induced by protein antigens required immunization: low doses of antigens

IHL Exam 2 (14 decks)

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