BIOL 435 Ch. 11 p.1 (B-Cell Activation, etc.)

Question 1

clonal selection hypothesis

Answer 1

• each B-cell bears a single type of Ig receptor

- on stimulation, each cell will create a clone of cells bearing the same Ag receptor as the original

Question 2

2 B-cell responses elicited by distinct Ag types

Answer 2

• T-dependent (TD) responses

- T-independent (TI) responses

Question 3

TD responses

Answer 3

• require help from T-cells

- are typically generated upon recognition of protein Ag

Question 4

TI responses

Answer 4

• do not require T-cell help

- generated upon exposure to multivalent/polymerized Ag

Question 5

TI-1 Ag

Answer 5

-binds to B-cell through PRRs and mIgs

Question 6

TI-2 Ag

Answer 6

-cross-link large numbers of BCRs

Question 7

TD B-cell response

Answer 7

• B-cells bind Ag via BCR
• induces initial activation and proliferation events
• some Ag is internalized, processed, and presented with MHC II
• TH cells provide conditions for differentiation and memory cell production

Question 8

proliferation

Answer 8

-induces formation of germinal centres in lymph nodes/spleen

Question 9

B-cells differentiate into 3 pathways

Answer 9

1. Form a primary focus of Ab-secreting plasma cells
2. IgM-bearning memory cell
3. Enter germinal centre-differentiate

Question 10

small soluble Ag

Answer 10

-acquired from lymphatic circulation by follicular B-cells

Question 11

larger Ag

Answer 11

• captured by subscapsular sinus macrophages

- handed off to B-cells in the follicles

Question 12

FDCs

Answer 12

• follicular dendritic cells

- serve as Ag concentration site for future selection and differentiation

Question 13

BCRs cluster upon Ag binding

Answer 13

• molecules move into lipid rafts
• allows association of BCR ITAM signalling molecules triggering B-cell sigalling
• involves a series of SMAC-integrin-actin interactions

Question 14

SMAC

Answer 14

-supramolecular activation cluster

Question 15

B-cell signal transduction cascade

Answer 15

-due to Ag binding to BCR
-signalsome formation and ITAM phosphorylation
-3 co-receptors propagate Ag-BCR signals
>CD19, CD21, CD81
*leads to survial, proliferation and differentiation of the B-cell

Question 16

CD21

Answer 16

-binds to complement fragment C3d enhancing Ag signalling

Question 17

Ag can be endocytosed

Answer 17

• once bound to BCR
  1. Ag cleaved from surface of APC by B-cell derived lysosomal proteases
  2. Ag then processed via the exogenous presentation pathway and presented in MHC II

Question 18

actomyosin fibers of B-cell

Answer 18

-exert a pulling force on BCR that pulls Ag from APC

Question 19

Ab-forming cells in primary foci

Answer 19

• no somatic hypermutation
• provide high quantities of specific Abs early (5-6days) in immune response
• secretede IgM and IgG reduce microbial numbers

Question 20

initiate germinal centre

Answer 20

• require CD40/CD40L interactions between B/T cells

- consist of dividing B-cells, FDC, TFH cells and macrophages: forming dark and light zones

Question 21

dark zone

Answer 21

• densely packed with proliferating B-cells

- location of somatic hypermutation

Question 22

light zone

Answer 22

• B cells interact with TFH cells and FDCs

- B-cells bearing high-affinity, mutated BCR are selected

Question 23

what occurs in germinal centre?

Answer 23

-B-cell proliferate
-somatic hypermutation
>Ig variable regions undergo extremely high rates of mutation (1/1000bp/generation)
-new BCRs are tested

Question 24

BCRs tested

Answer 24

• BCRs with higher affinity are selected for=proliferate

- BCRS with lower affinity or none=die by apoptosis

Question 25

somatic hypermutation (SHM)

Answer 25

-produces individual point mutations in Ig H- and L- chain rearrangements
>mutations increase over time and with repeated exposures
>followed by affinity selection result in increased infinity for Ag over time

Question 26

activated-induced deaminase (AID)

Answer 26

-mediated SHM
-enzyme expressed with DNA pol
-breaks DNA, making it need to be repaired
>not repaired well
-also class switch recombination

Question 27

mutational apparatus targetting

Answer 27

• mutational hot spots are sequence motifs far more likely to be targeted
• mutations are prevented in non-Ig areas