61-Mature B Cell Responses Flashcards Preview

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Flashcards in 61-Mature B Cell Responses Deck (30)
1

basic signals required for b cell activation

recognition and binding of Ag
BCR clustering
signal
1-BCR signaling cascade, activation
signal
2-co stimulation, survival
signal
3-cytokine stimuli, expansion and differentiation

2

BCR structure

BCR-Ag binding site, transmembrane, no signaling ability

3

CD79 a/b

adapter molecules
connect surface Ig to intracellular signaling pathway

4

ITAM

tyrosine target that gets phosphorylated to attract signal transduction

5

CD19, CD21, CD81

coreceptor molecules, amplify CD79a/b

6

binding and clustering

Ag binds to BCR, BCR clusters which leads to activation of signal transduction cascade initiated by tyrosine motifs

7

TI Ags

display epitopes recognized by BCR
composed of lipid or carb
activate innate immunity (pattern recognition receptors, complement)
activate B cells

8

TD Ags

display epitopes recognized by BCR
composed of protein
DO NOT activate innate immunity
requires CD4 T helper to provide signals 2 and 3

9

Activation of B cells by TI

signal 1- binding, clustering, signal transduction
signal 2- costimulation from innate signals (TLR, PAMPs, complement)
signal 3- cytokines for expansion and differentiation from innate or T cells (DC, macrophages, neutrophils, NK cells)

10

Marginal zone B cells

TI antigens
epitopes are lipid or carb
rapid BCR and TLR response
does not use CD4 T helper cells

11

Key features of TI B cell response

rapid- do not need CD4T help
Major Ab is IgM
no germinal center-plasma cells short lived, no memory b cells, TI Ab response low affinity

12

Activation of B cells by T cell after infection

signal 1-peptides presented in MHC class II
signal 2- follicular helper cells express CD 154 which bind CD40
signal 3- cytokines to direct CD4 to expansion and differentiation
**use t follicular helper cells for B cell

13

T follicular helper cell

ability to enter B cell follicles and provide signals 2 and 3 to b cells

14

CD 154

expressed by activated T helper cells, ligand for CD 40

15

function of dendritic cells in B cell activation

bring Ag into B cell follicles
epitopes recognized by B cells
Ags bound by BCR-signal cascade initiated by crosslinking and CD79
Ag processed and presented in MHC

16

CD40

constitutive expression on surface of B cells

17

movement of T and B cells to border

after activation the cells coexpress CCR7 and CXCR5 to force movement to border

18

differentiation at T cell zone

1 subset quickly differentiates into antibody secreting cells (plasma cells), short lived, quick response
1 subset migrates back to follicle to seed germinal center response (lose CCR7 and keep CXCR5)

19

cognate interaction

cell driven activation of B cells

20

Germinal center

proliferation and differentiation of activated Ag specific B cells

21

cells in germinal center

Ag specific B cells activated by T follicular helper cells
cells that have lost CCR7 and kept CXCR5
follicular dendritic cells
macrophages to digest apoptotic B cells

22

processes in germinal center

proliferation-mitotic expansion
isotype switching- change heavy chain, requires continued signals 2 and 3
affinity maturation- BCR for Ag becomes higher affinity, requires signals 2 and 3
terminal differentiation- plasma or memory cells

23

isotype switching

in germinal center, change heavy region
selected switch regions brought into close proximity forming a loops
DNA excised and discarded
broken strands ligated
VDJ now proximal to new constant region

24

somatic hypermutaion

B cells given signals by T follicular helper cells to start mutation process
nucleic acid interchanges, mutations can be progressive and accumulate
lead to altered amino acid sequence at Ag binding site

25

affinity selection

limited amounts of original Ag
B cells must compete for this Ag to survive
grab with BCR, ingest, process, and present peptides to provide survival signals
without this they die
mutations with higher affinity=advantage and become plasma or memory cells

26

terminal differentiation

plasma cells or memory B cells

27

plasma cells

secrete antibodies
initially found in lymphoid organs, then move to bone marrow where they survive for years

28

memory b cells

isotype switched
high affinity
long lived
recirculate through SLO
facilitate secondary response when same Ag enters

29

secondary response

same Ag enters, quicker activation with T helper cells, produce high affinity Abs, destroy pathogens before infection

30

vaccination

TD antigens induce B cell activation
germinal center reactions
high affinity, switched Abs
plasma cells
memory b cells