III - B cells Flashcards

1
Q

what occurs to an activated B cell

A

becomes either a memory or plasma cell

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2
Q

feature of a memory cell

A

has a long lifespan
has the same BCR as parent cell

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3
Q

feature of plasma cell

A

live for only a few days
secrete 2000 antibodies per/s

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4
Q

what is hyper IgM syndrome

A

primary immunodeficiency in which patients patients only express the 1st antibody type -
IgM

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5
Q

what is the BCR

A

a membrane bound antibody

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6
Q

what is the structure of an antibody

A

2 light chains - 25kDa
2 heavy chains - 50kDa
variable region
constant region

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7
Q

where does the antigen bind to an antibody

A

the variable region

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8
Q

what does the constant region possess

A

the effector function activity

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9
Q

how is the isotype of an antibody determined

A

the carboxy terminus of the heavy chain

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10
Q

what is a CDR

A

a complimentary determining region

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11
Q

where are CDR1/2

A

they are where the V gene segments are located

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12
Q

what is the unique feature of CDR3

A

it is the most variable - formed by the heavy chain

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13
Q

what does the periphery regard to

A

outside the lymphoid organs

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14
Q

what is the earliest class of antibody and what is expressed next

A

IgM
IgD

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15
Q

what antibodies are made in response to challenges in the periphery

A

IgA
IgG
IgE

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16
Q

where are early B-cells located

A

in bone marrow

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17
Q

where is IgM expressed in the B-cell in bone marrow

A

on the cell surface

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18
Q

how are B-cell receptors rearranged

A

as in T-cells

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19
Q

where do cells move in the B-cell maturation process

A

to the spleen

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20
Q

where is IgD expressed after B-cells move to the spleen what is it independent of

A

on the cell surface
independent of antigens

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21
Q

how does maturation begin

A

in an antigen-dependent manner

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22
Q

what are essential to the survival of early B-cells in bone marrow

A

stromal cells in the bone

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23
Q

what is the function of VCAM-1 on stromal cells and what does it convert an early lymphoid cell into

A

binds VLA-4 on the B-cell
early pro-B-cell

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24
Q

function of SCF from the stromal cells and what does it convert an early pro-B-cell into

A

binds cKit on the B-cell
late pro-B-cell

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25
Q

function of IL-7 on the stromal cells
and what does it convert a late pro-B-cell into

A

binds IL-7 receptors on B-cells
an immature B-cell

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26
Q

in VJD recombination - heavy chain, what is the purpose of the leader sequence

A

takes the protein into the cells secretory pathway to be cleaved

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27
Q

what is the 1st rearrangement that occurs in the heavy chain

A

Dh region joins with the Jh region
DJh region

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28
Q

what is the 2nd rearrangement in the heavy chain

A

Vh rearranged to DJh
makes the complete Vh region exon

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29
Q

what happens when the complete Vh region exon is created

A

transcription occurs

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30
Q

in the heavy chain what undergoes RNA splicing in heavy chain recombination

A

joins the assembles V region exon to the C region exon

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31
Q

how many segments are there actually in the heavy chain

A

V - 65
D - 27
J - 6

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32
Q

where does recombination occur at

A

recombination signal sequence

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33
Q

structure of RSS’s

A

made up of a heptamer 12 or 23 base pairs
nonamer 9 base pairs

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34
Q

what are the 23/12 base pairs brought together by

A

proteins which binds spacer length

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35
Q

what is the side-effect of imprecise joining in VDJ recombination

A

creates lots of diversity

36
Q

what occurs if the V and the J segments have the same orientation

A

the intervening DNA is cut out into a circle

37
Q

what is occurs if the V and the J segments are in initially opposite directions

A

complex looping of the DNA is required

38
Q

what is the difference between the light and heavy chain in terms of VDJ recombination

A

light chain contains only one C region and no D regions

39
Q

what is the 1st rearrangement that occurs in the light chain during VDJ recombination

A

Vl and Jl rearrangement
forms VJl
then transcribed

40
Q

what is the 2nd rearrangement in the light chain

A

brings the V region exon next to the C region exon

41
Q

what are the actual amount of segments in the light chain

A

V - 30-40
J - 4-5

42
Q

how are immunoglobulin genes organised

A

3 clusters, each on a separate chromosome
2 light chain loci, each slightly different

43
Q

what does the recombination machinery bind to

A

both the light chain loci
preferentially targets K
therefore more K antibodies than L

44
Q

what is combinational diversity

A

from the different combination of gene segements

45
Q

what is junctional diversity

A

from the addition of nucleotides when recombination occurs

46
Q

outline how junctional diversity is achieved

A

RSS sequences are brought together
RAG complex nicks and opens DNA
palindromic nucleotides are added
N nucleotides are added TdT
unpaired nucleotides are excised and DNA is repaired

47
Q

where is CDR3 located

A

falls at the V/D/ J segments

48
Q

what happens if an immature B-cell recognises a self-antigen and what does this lead to

A

its surface IgM will cross link
apoptosis

49
Q

epitopes are usually what

A

long polysaccharides with repeating sugar sequences

50
Q

what do epitopes bind and what does it lead to

A

IgM and IgD
a strong activation signal is generated
B-cells release IgM

51
Q

what is linked recognition

A

antigen-dependent maturation
requires T-cell help which recognises the same antigen
like 2FA for B-cells

52
Q

outline steps 1/2 T-cell help in antigen dependent B-cell maturation

A

1 - BCR binds to an antigen
2 - antigen is internalised and presented on MHC class II molecules

53
Q

outline steps 3/4 T-cell help in antigen dependent B-cell maturation

A

3 - T-helper cells recognise MHC class II antigen through their TCR - release cytokine help for B-cells
4 - B-cells release antigen specific antibodies

54
Q

what expresses CD40L and what is its function

A

T-helper cells
stimulates B cells to proliferate and become plasma cells

55
Q

function of IL4/5/6

A

IL4 - drives proliferation
IL5/6 - drive plasma cells

56
Q

where are B cells temporarily trapped and why

A

in the T cell zone
to come into contact antigen and T helper cells

57
Q

what is the germinal centre and how long does it take to form

A

made up of proliferating B cells
takes 7-10 days to form after infection

58
Q

what is the mantle zone made up of

A

resting B cells displaced by activated B cells

59
Q

what do B cells undergo in the germinal centre

A

somatic hypermutation
affinity maturation
class switching

60
Q

as B cells multiply, what happens at the V regions of both chains

A

point mutations occur - on purpose
leads to CDR’s

61
Q

what is the function of newly generated CDR’s from point mutations

A

some new CDR’s can bind antigen better than the original
are then preferentially chosen to mature into plasma cells
process called affinity maturation

62
Q

what is the function of affinity maturation

A

allows B cells to develop receptors with hugely increased ability to recognise antigens
more B cells that are more antigen specific

63
Q

what is AID

A

cytidine deaminase that introduces nicks in the DNA that are ‘repaired’
cause of the point mutations

64
Q

what is class switching

A

changes to the IgG, IgA, or IgE during the immune response after T cell help

65
Q

what is the purpose of class switching

A

allows a different C region to be used in antibody with a specific antigen binding region

66
Q

what is changed in class switching and why

A

only the constant region changes - so binds to the same antigen
but the outcome of binding is altered

67
Q

when is IgM expressed

A

before somatic hypermutation

68
Q

features of IgD

A

expressed upon cell activation
is a cell-surface antigen receptor

69
Q

features of IgG

A

opsonises pathogens for phagocytosis
most abundant
can cross the placenta
monomeric

70
Q

features of IgA

A

functions on epithelial surfaces - neutralisation
mucosal antibody

71
Q

function of IgE

A

localises to mast cells on the mucosa

72
Q

what antibodies are secreted in neutralisation

A

IgM - +
IgG - ++
IgA - ++

73
Q

what antibodies are secreted for opsonisation

A

IgM - +
IgG - ++
IgA ++

74
Q

what antibodies are secreted for sensitisation for killing by NK cells

A

IgG

75
Q

what antibodies are released for sensitisation to mast cells

A

IgG - +
IgE - +++

76
Q

what antibodies activate the complement system

A

IgM - +++
IgG - ++
IgA - +

77
Q

which antibodies are transported across the epithelium

A

IgM - +
IgA +++

78
Q

which antibodies diffuse into extravascular sites

A

IgG - +++
IgA - ++

79
Q

which antibodies are released in response to a viruses and extra-cellular bacteria (in general)

A

IgM
IgG
IgA

80
Q

what is released in response to intracellular bacteria

A

only T-cells

81
Q

what antibody is released in response to fungi and protozoa

A

IgG

82
Q

what antibody is released in response to worms

A

IgE

83
Q

what does Fc bind to

A

Fc receptors

84
Q

how do phagocytic cells internalise antigens

A

through Fc receptor binding

85
Q

natural killer cells kill target cells through what

A

antibody dependent cell mediated cytotoxicity
(ADCC)

86
Q

what phagocytic cells do not produce cytokines

A

naive B cells

87
Q

what do B cells generally produce instead of cytokines and for what

A

chemokines
induce migration of T cells - assist with T cell help