B cell activation and antibody production (part II)

Question 1

B cells must etner ____ to become mature

Answer 1

spleen

Question 2

precursor B cells – ________ –> immature B cell

Answer 2

VDJ recombination

Question 3

membrane BCR vs Soluble BCR:

difference are in ____ region due to ____ ____

Answer 3

tail alternative splicing

Question 4

____ and ____ are co-expressed on naive B cells through the mechanism of alternative splicing of the primary mRNA transcript of the Ig heavy chain locus

Answer 4

IgM and IgD

Question 5

expression of AID (activation-induced [cytosine] deaminiase) requires ____ - ____interaction

Answer 5

CD40 - CD40L

Question 6

CD40L is on T helper cells, so AID is only present in ____ responses (protein Ag only)

Answer 6

thymus (T-cell) dependent

Question 7

in the GCs, B cells express activation induced deaminase (AID) which initiates somatic ____ and affinity ____

Answer 7

hypermutation

affinity

Question 8

affinity maturation is observed only in Ab responses to ____ Ags

Answer 8

thymus-dependent (TD)

Question 9

affinity maturation occurs within the ____ , where somatically mutated BCRs undergo selection on antigen retained on ____

Answer 9

GCs

FDCs (follicular dendritic cells)

Question 10

Ag retained on FDCs are retained in the form of ____ complexes and involves the interaction of both ____ receptors and FcgammaRIIB with these immune complexes on FDCs

Answer 10

immune

complement

Question 11

mechanism of affinity maturation:

1. Dark Zone:
   
   1. AID creates ____ mutations in ____ regions (also called somatic hypermutation)
2. light zone processes:
   
   1. changed BCR is exposed to Ag on ____
   2. increased affinity receptors receive stimulus to ____ , decreased affinity receptors do not
   3. process repeats so further ____ increases can occurs

Answer 11

1. Dark Zone:
   
   1. point V
2. light zone processes:
   
   1. FDC
   2. live
   3. affinity

Question 12

B cell proliferation takes places in the ____ zone of the GC

Answer 12

dark

Question 13

dark zone:

1. cognate contact between T_FH cell recognizing the Ag presented by B cells ____ B cell
2. the T cell-derived cytokines stimulate proliferation and ____ of B cell clone
3. the ____-____ interaction activates somatic hypermutation in proliferating B cells leading to diversification of BCR
4. T cell-derived cytokines also stimulate ____ switch of Abs produced by activated B cell

Answer 13

1. activates
2. expansion
3. CD40-CD40L
4. class

Question 14

affinity maturation results from repeated ____

Answer 14

mutations

Question 15

light zone:

1. B cell with mutated BCR performs ____ scanning and if BCR affinity is increased then B cell proceeds to start proliferation process over again
2. if the mutated BCR has low affinity then this B cell undergoes ____

Answer 15

1. FDC
2. apoptosis

Question 16

how increased affinity is determined:

1. mutations correlate with increasing ____ of the Abs for the Ag that induced the response
2. Ag recognition promotes expression of ____
3. Ag recognition stimulates production of ____ inhibitor

Answer 16

1. affinities
2. anti-apoptotic Bcl-2
3. Fas

Question 17

stronger ____ → more stimulation → more Bcl-2 → stronger T cell interations (CD40-CD40L) → more Fas inhibitor

Answer 17

affinity

Question 18

many tumors of B cells, B cell lymphomas develop from B cells in ____

its caused by chromsomal ____ of various oncogenes into Ig gene loci

the DNA breaks associated with somatic hypermutation and isotype switching facilitate incorporation of ____

Answer 18

GCs

translocations

oncogenes

Question 19

____ can contribute to the pathogenesis of autoimmunity

Answer 19

GCs

Question 20

Ig isotype switching:

1. isotype switching primarily occurs in the ____ and is driven by ____ cells
2. some isotype switching may occur in B cells in ____ foci and driven by extrafollicular Th cells
3. class-switching occurs in resonse to changing the ____ regions of the heavy chain
4. Abs specificity which is determined by the ____ regions in the class-switched Abs remains unaltered

Answer 20

1. GCs T_FH
2. extrafollicular
3. constant
4. variable

Question 21

intracellular pathogens → increased ____ differentiation → increases ____ → ____ isotype switching

Answer 21

Th1

IFN-gamma

IgG

Question 22

helminth infections → increased ____ differentiation → increased ____ → ____ isotype switching

Answer 22

Th2

IL-4

IgE

Question 23

mucosal tissues produce ____ and ____ → increased IgA isotype switching

Answer 23

TFG-beta and BAFF

Question 24

B cells in different anatomic sites switch to different Ab isotypes, this is controlled by local cytokine ____

Answer 24

milieu

Question 25

both isotype switching and affintiy maturation depend on \_\_\_\_

Answer 25

AID (activation-induced deaminase

Question 26

CD40 engagesment induces \_\_\_\_

Answer 26

AID

Question 27

somatic mutation of ____ genes genreates Abs with different affinities for Ag

Answer 27

Variable

Question 28

binding of the B cells to Ag displayed on ____ is necessary to rescue the B cells from apoptosis

Answer 28

FDCs

Question 29

B cells that have undergone somatic mutation migrate into the FDC-rich ____ zone of the GC

Answer 29

light

Question 30

_survival of B cells with high-affinity BCRs_ 1. Ag recognition (presented by FDC) induces expression of anti-apoptotic proteins of the ____ family 2. high affinity B cells will preferentially endocytose and present the Ag for ____ cells in the GC which signal via CD40L to promote the survival of the B cells 3. expression of engogenous inhibitors of ____ in high-affinity B cells may be activatd when their BCRs recognize Ag and thus be protected from death

Answer 30

1. Bcl-2 2. T_FH 3. Fas

Question 31

_long-lived plasma cells:_ 1. generated in T-\_\_\_\_ responses to protein Ag in GC 2. ____ cytokine from T_FH cells stimulate differentiation 3. ____ provides survival signals

Answer 31

1. T-dependent 2. IL-21 3. BAFF

Question 32

_short-lived plasma cells:_ are generated in ____ compartments during T-\_\_\_\_ responses

Answer 32

extrafollicular T-independent

Question 33

plasmablasts are generated in GC and enter the circulation and home to the ____ \_\_\_\_ wher they differentiate into long-lived plasma cells

Answer 33

bone marrow

Question 34

long-lived plasma cells are maintained by ____ allowing the cells to survive for long periods often as long as the life span of the host

Answer 34

BAFF

Question 35

_memory B cells:_ 1. memory cells are generated mainly in the GCs for T-\_\_\_\_ protein Ags 2. acquire the ability to survice for long periods of time without continuing ____ stimulation 3. typically are higher ____ and isotyped switched 4. constitutively express ____ resulting in their long survival 5. can be found both in ____ and in \_\_\_\_

Answer 35

1. dependent 2. Ag 3. affinity 4. Bcl-2 5. secondary lymphoid organs and in circulation

Question 36

_TI Ab responses:_ 1. typically respond to \_\_\_\_, ____ Ags; these are not presented on ____ and don't activate T cells 2. typically no isotype switching, ____ predominants

Answer 36

1. multivalent , nonprotein MHC 2. IgM

Question 37

_most TI Ags are multivalent:_ 1. the majority of TI Ags are multivalent, being composed of ____ identical Ag \_\_\_\_ 2. such multivalent Ags may induce maximal \_\_\_\_of the BCR complex on specific B cells leading to activation ____ a requirement for cognate T cell help

Answer 37

1. repeated epitopes 2. cross-linking without

Question 38

MZ B cells are a distinct population of B cells in the spleen that mainly respond to

Answer 38

polysaccharides

Question 39

what B cells respond primarily to TI Ags

Answer 39

MZ B cells B-1 cells

Question 40

the most important TI Ags are

Answer 40

polysaccharides, glycolipids, and nucleic acids

Question 41

many polysaccharides activate the complement system by the ____ pathway, generating C3b which first binds to teh Ag and then processed into C3d recgonzied by CR2 on B cell

Answer 41

alternative

Question 42

memory occurs only if the vaccines are able to activate ____ , therefor effective vaccines must induce both affinty maturation and memory B cell formation

Answer 42

T helper cells

Question 43

_conjugate vaccines:_ 1. TI Ags cannot produce memory because they are ____ Ags 2. to resolve this, non-protein Ag (e.g. polysaccharide) is covalently linked to a foreign protein to form the equivalent of a ____ \_\_\_\_

Answer 43

1. non-protein 2. hapten-carrier conjugate

Question 44

_how are vaccines produced for TI Ags_ 1. attach the TI Ag to a ____ (called a carrier). 2. the protein is loaded onto MHC of APCs and the TI Ag is what's recognized by the \_\_\_\_ 3. this allows for presentation of non-protein Ags to T cells so ____ interaction can occur and generate long lived plasma cells and memory

Answer 44

1. protein 2. TCR 3. CD40-CD40L

Question 45

_Ab production feedback inhibition_ 1. ____ (CD32) is a low affinity receptor for IgG found on B cells 2. because it is low affinity, IgG will tend to form a complex with ____ first and then that complex sill bind with BCRs bringint IgG into proximity with FcgammaRIIB 3. when IgG binds FcgammaRIIB it inhibits signals generated by BCR complex recognition of \_\_\_\_ 4. this results in feedback ____ for production of IgG

Answer 45

1. FcgammaRIIB 2. Ag 3. Ag 4. inhibition