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Clinical Immunology > B cells and Natural Killer (NK) cells > Flashcards

B cells and Natural Killer (NK) cells Flashcards

1
Q

what do b cells arise from?

A

Like T cells, B cells arise
from a common lymphoid
progenitor

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2
Q

Unlike T cells, which
migrate to the thymus, B
cells are selected in the

A

bone marrow (BM)

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3
Q

Like T cells, B cells re

A

recirculate

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4
Q

Like T cells, B cells recirculate; …

A

… tissues & lymphatics until they are challenged by
antigen

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5
Q

Unlike T cells, B cells DO NOT…

A

…require Ag presented on MHC
for activation

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6
Q

Unlike T cells, B cells DO NOT require Ag presented on MHC
for activation and can…

A

…interact directly with soluble Ag, moreover B cells present Ag on MHC-II to T cells.

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7
Q

B cells (B lymphocytes) are so called because it was established that in
birds B cells develop in the…

A

… bursa Fabricus of the cloaca

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8
Q

Early experiments illustrated that removal of hatchling bursa prevented

A

antibody production (humoral response)

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9
Q

Discovery of the thymus came shortly after
and was noted for

A

its role in cellular immunity

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10
Q

Remember, in adults haematopoiesis takes place in the…

A

… bone marrow (BM) of
the long bones, pelvis and sternum

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11
Q

B cells develop and mature in the

A

BM

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12
Q

B cells develop and mature in the BM through …

A

… pro-B > precursor B > B cell

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13
Q

Undergo Ig gene arrangement to

A

reach maturity

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14
Q

10% B cells mature and exit

A

BM

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15
Q

10% B cells mature and exit BM but

A

are naive until Ag is encountered

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16
Q

Die in periphery after a few days if

A

Ag is not encountered

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17
Q

how many checkpoints in B cell development?

A

3 check-points

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18
Q

what are the 3 check-points in B cell development?

A

1) (CD79a) and (CD79b) expression on late pro-B cells;
CD79 molecules are important for signal transduction during B cell maturation.
2) Successful recombination of H-chain locus.
3) Successful recombination of L-chain locus .

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19
Q

what do mature B cells express?

A

surface IgD > IgM (IgM following BCR activation).

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20
Q

B cell self tolerance initiates when…

A

… IgM expression begins
(IgM is the first BCR to appear on immature B cell surface)

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21
Q

slide 10

development of B cells (lineage)?

A
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22
Q

where does the two check points occur in b cells?

A
  • Check point at late pro-B cell stage establishes functional H-chain
  • Check point at pre-B cell stage establishes functional L-chain
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23
Q

go learn slide 11

A
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24
Q

B cells do not need to recognise

A

self (MHC) like T cells do

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25
Q

B cells do not need to recognise self (MHC) like T cells do; however B
cells must

A

ignore (tolerate) self (MHC)

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26
Q

Negative selection processes ensure that

A

B cells ignore self

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27
Q

B cells that interact with multivalent cell surface self (MHC): cross linking of BCRs (high avidity) causes immature B cell to

A

die (apoptosis)

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28
Q

B cells that interact with multivalent cell surface self (MHC): cross
linking of BCRs (high avidity) causes immature B cell to die (apoptosis)

But a

A

receptor rearrangement stage before death is a 2nd chance to produce a non-self reactive BCR.

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29
Q

BCR that react with soluble self Ag (low valence) down regulate

A

its IgM, so has IgD is alone.

Now its anergic (non-reactive).

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30
Q

Remember, cell surface
receptors are the

A

sensory components of the immune cell

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32
Q

BCR-Ag interaction activates…

A

… LYN which phosphorylates Igβ (CD79b) and CD19of the (CD19/CD21/CD81complex)

33
Q

A cascade of phosphorylation events occur
culminating in

A

RAS / PI3-kinase activation - triggering proliferation of the cell.

34
Q

LYN is a

A

proto-onco gene

36
Q

InsP3 causes

A

Ca2+ spikes

37
Q

Differential InsP3 mediated Ca2+ spikes and (or) oscillation(s) mediate …

A

… the activation of NF-κB and (or) NFAT transcription factors

38
Q

what is NF- κB ?

A

nuclear factor kappa-light-chain-enhancer of activated B cells

39
Q

what is NFAT ?

A

nuclear factor of activated T cells

40
Q

NFAT supports

A

proliferation

41
Q

CD22and FcγRIIB1 are

A

negative co-receptors

42
Q

As with T cells there are

A

various B cell subsets

43
Q

the most abundant b cell cubset

A

B-2 B cells

44
Q

what are the different subsets of b cells?

A

B-2 B cells (most abundant, generally named ‘B cell’), B-1 B cells, follicular B cells, marginal zone B cells, regulatory B cells and Plasma B cells

45
Q

Two principle methods for B cell activation are

A

1) T-Dependent (TD)
2) T-Independent (TI)

46
Q

The TD response is mediated by

A

B-2 B cells interacting with TD antigens

47
Q

describe the TD response ?

A

(1) TD antigen crosslinks BCR, some BCR TD antigen complex is internalised, processed and presented on MHC-II .
(2) TH cell engages with B cell via complementary TCR and co-stimulation to B cell via CD40 .

48
Q

For TI responses, there are two mechanisms whch are

A

1) TI-1
2) TI-2

49
Q

What happens in TI-1 ?

A

B cell binds antigen at BCR and
receives a co-stimulation via a ‘toll-like receptor’ (TLR)
from a super antigen such as LPS

50
Q

what happens in TI-2 ?

A

TI-2 antigens are often bound to complement protein C3d, which crosslinks BCR (12 – 16 crosslinks required) with co-stimulation from CD21.

51
Q

Forgoing T cell involvement speeds up the…

A

… B cell (humoral) response, however cytokines (secreted by TH cells) are missed

52
Q

Forgoing T cell involvement speeds up the B cell (humoral) response, however cytokines (secreted by TH cells) are missed, thus…

A

… Ig class switching fails to take place

53
Q

B cells enter lymph node via …

A

the high endothelial venules into the ‘T cell zone’ where Ag challenged B cell interact with TH cells.

54
Q

TD activated B cells migrate to

A

germinal centre -> clonal proliferation in dark zone

55
Q

Clones with high Ag affinity are selected in

A

basal light zone (differentiate)

56
Q

Plasma cells / memory precursors proliferate in

A

apical light zone

57
Q

TH2 cells are central to…

A

… B cell TD activation, proliferation and Ig class
switching

58
Q

IL-4 (interleukin 4), IL-5 and IL-6 plus CD40 ligation mediate …

A

… clonal proliferation and differentiation to IgM secreting plasma cells

60
Q

Class switching requires

A

cross-talk between CD40 and IL-4

61
Q

CD40 activation is required for

A

NF-κB activation (nuclear
localisation)

62
Q

IL-4 is required for

A

STAT6 activation

63
Q

IL-4 is required for
STAT6 activation, which
binds

A

upstream of Sε IgE constant chain gene segment

64
Q

IL-4 is required for
STAT6 activation, which
binds upstream of Sε
IgE constant chain gene
segment > promoting …

A

… AID (activation induced
deaminase) binding and
subsequent genomic splicing

65
Q

B cells are also important in …

A

… viral infections

66
Q

B cell receptor binds

A

viral coat protein

67
Q

B cell receptor binds
viral coat protein
Viral coat protein is …

A

… processed and presented on MHC-II

68
Q
  • B cell receptor binds
    viral coat protein
  • Viral coat protein is processed and presented on MHC-II
  • B cells …
A

… differentiate and plasma cells secrete viral protein specific Ab

  • opsonising
  • neutralising
69
Q

NK cells account for

A

10% of all lymphocytes

70
Q

NK cells differentiate early
from

A

the T cell lineage

71
Q

NK cells do not express

A

T or B cell markers (CD3,
CD4, CD8 or CD19)

72
Q

NK cells are

A

innate (not adaptive) in function

73
Q

NK cells are innate (not adaptive) in function &
are believed to be…

A

… more primitive in evolutionary terms

74
Q

General NK immunophenotype is:

A

CD3-
CD19-
CD56+

Clinical Immunology (8 decks)

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