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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
B cells do not need to recognise self (MHC) like T cells do; however B cells must
ignore (tolerate) self (MHC)
26
Negative selection processes ensure that
B cells ignore self
27
B cells that interact with multivalent cell surface self (MHC): cross linking of BCRs (high avidity) causes immature B cell to
die (apoptosis)
28
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
receptor rearrangement stage before death is a 2nd chance to produce a non-self reactive BCR.
29
BCR that react with soluble self Ag (low valence) down regulate
its IgM, so has IgD is alone. Now its anergic (non-reactive).
30
Remember, cell surface receptors are the
sensory components of the immune cell
31
13
32
BCR-Ag interaction activates...
... LYN which phosphorylates Igβ (CD79b) and CD19of the (CD19/CD21/CD81complex)
33
A cascade of phosphorylation events occur culminating in
RAS / PI3-kinase activation - triggering proliferation of the cell.
34
LYN is a
proto-onco gene
35
15
36
InsP3 causes
Ca2+ spikes
37
Differential InsP3 mediated Ca2+ spikes and (or) oscillation(s) mediate ...
... the activation of NF-κB and (or) NFAT transcription factors
38
what is NF- κB ?
nuclear factor kappa-light-chain-enhancer of activated B cells
39
what is NFAT ?
nuclear factor of activated T cells
40
NFAT supports
proliferation
41
CD22and FcγRIIB1 are
negative co-receptors
42
As with T cells there are
various B cell subsets
43
the most abundant b cell cubset
B-2 B cells
44
what are the different subsets of b cells?
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
Two principle methods for B cell activation are
1) T-Dependent (TD) 2) T-Independent (TI)
46
The TD response is mediated by
B-2 B cells interacting with TD antigens
47
describe the TD response ?
(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
For TI responses, there are two mechanisms whch are
1) TI-1 2) TI-2
49
What happens in TI-1 ?
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
what happens in TI-2 ?
TI-2 antigens are often bound to complement protein C3d, which crosslinks BCR (12 – 16 crosslinks required) with co-stimulation from CD21.
51
Forgoing T cell involvement speeds up the...
... B cell (humoral) response, however cytokines (secreted by TH cells) are missed
52
Forgoing T cell involvement speeds up the B cell (humoral) response, however cytokines (secreted by TH cells) are missed, thus...
... Ig class switching fails to take place
53
B cells enter lymph node via ...
the high endothelial venules into the ‘T cell zone’ where Ag challenged B cell interact with TH cells.
54
TD activated B cells migrate to
germinal centre -> clonal proliferation in dark zone
55
Clones with high Ag affinity are selected in
basal light zone (differentiate)
56
Plasma cells / memory precursors proliferate in
apical light zone
57
TH2 cells are central to...
... B cell TD activation, proliferation and Ig class switching
58
IL-4 (interleukin 4), IL-5 and IL-6 plus CD40 ligation mediate ...
... clonal proliferation and differentiation to IgM secreting plasma cells
59
21
60
Class switching requires
cross-talk between CD40 and IL-4
61
CD40 activation is required for
NF-κB activation (nuclear localisation)
62
IL-4 is required for
STAT6 activation
63
IL-4 is required for STAT6 activation, which binds
upstream of Sε IgE constant chain gene segment
64
IL-4 is required for STAT6 activation, which binds upstream of Sε IgE constant chain gene segment > promoting ...
... AID (activation induced deaminase) binding and subsequent genomic splicing
65
B cells are also important in ...
... viral infections
66
B cell receptor binds
viral coat protein
67
B cell receptor binds viral coat protein Viral coat protein is ...
... processed and presented on MHC-II
68
- B cell receptor binds viral coat protein - Viral coat protein is processed and presented on MHC-II - B cells ...
... differentiate and plasma cells secrete viral protein specific Ab - opsonising - neutralising
69
NK cells account for
10% of all lymphocytes
70
NK cells differentiate early from
the T cell lineage
71
NK cells do not express
T or B cell markers (CD3, CD4, CD8 or CD19)
72
NK cells are
innate (not adaptive) in function
73
NK cells are innate (not adaptive) in function & are believed to be...
... more primitive in evolutionary terms
74
General NK immunophenotype is:
CD3- CD19- CD56+
75
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Clinical Immunology (9 decks)

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