B cell activation and antibody production (part II) Flashcards

1
Q

B cells must etner ____ to become mature

A

spleen

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2
Q

precursor B cells – ________ –> immature B cell

A

VDJ recombination

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3
Q

membrane BCR vs Soluble BCR:

difference are in ____ region due to ____ ____

A

tail alternative splicing

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4
Q

____ 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

A

IgM and IgD

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5
Q

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

A

CD40 - CD40L

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6
Q

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

A

thymus (T-cell) dependent

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7
Q

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

A

hypermutation

affinity

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8
Q

affinity maturation is observed only in Ab responses to ____ Ags

A

thymus-dependent (TD)

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9
Q

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

A

GCs

FDCs (follicular dendritic cells)

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10
Q

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

A

immune

complement

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11
Q

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
A
  1. Dark Zone:
    1. point V
  2. light zone processes:
    1. FDC
    2. live
    3. affinity
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12
Q

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

A

dark

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13
Q

dark zone:

  1. cognate contact between TFH 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
A
  1. activates
  2. expansion
  3. CD40-CD40L
  4. class
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14
Q

affinity maturation results from repeated ____

A

mutations

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15
Q

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 ____
A
  1. FDC
  2. apoptosis
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16
Q

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
A
  1. affinities
  2. anti-apoptotic Bcl-2
  3. Fas
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17
Q

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

A

affinity

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18
Q

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 ____

A

GCs

translocations

oncogenes

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19
Q

____ can contribute to the pathogenesis of autoimmunity

A

GCs

20
Q

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
A
  1. GCs TFH
  2. extrafollicular
  3. constant
  4. variable
21
Q

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

A

Th1

IFN-gamma

IgG

22
Q

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

A

Th2

IL-4

IgE

23
Q

mucosal tissues produce ____ and ____ → increased IgA isotype switching

A

TFG-beta and BAFF

24
Q

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

A

milieu

25
Q

both isotype switching and affintiy maturation depend on ____

A

AID (activation-induced deaminase

26
Q

CD40 engagesment induces ____

A

AID

27
Q

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

A

Variable

28
Q

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

A

FDCs

29
Q

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

A

light

30
Q

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
A
  1. Bcl-2
  2. TFH
  3. Fas
31
Q

long-lived plasma cells:

  1. generated in T-____ responses to protein Ag in GC
  2. ____ cytokine from TFH cells stimulate differentiation
  3. ____ provides survival signals
A
  1. T-dependent
  2. IL-21
  3. BAFF
32
Q

short-lived plasma cells:

are generated in ____ compartments during T-____ responses

A

extrafollicular T-independent

33
Q

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

A

bone marrow

34
Q

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

A

BAFF

35
Q

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 ____
A
  1. dependent
  2. Ag
  3. affinity
  4. Bcl-2
  5. secondary lymphoid organs and in circulation
36
Q

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
A
  1. multivalent , nonprotein MHC
  2. IgM
37
Q

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
A
  1. repeated epitopes
  2. cross-linking without
38
Q

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

A

polysaccharides

39
Q

what B cells respond primarily to TI Ags

A

MZ B cells

B-1 cells

40
Q

the most important TI Ags are

A

polysaccharides, glycolipids, and nucleic acids

41
Q

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

A

alternative

42
Q

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

A

T helper cells

43
Q

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 ____ ____
A
  1. non-protein
  2. hapten-carrier conjugate
44
Q

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
A
  1. protein
  2. TCR
  3. CD40-CD40L
45
Q

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