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
function of IL-7 on the stromal cells and what does it convert a late pro-B-cell into
binds IL-7 receptors on B-cells an immature B-cell
26
in VJD recombination - heavy chain, what is the purpose of the leader sequence
takes the protein into the cells secretory pathway to be cleaved
27
what is the 1st rearrangement that occurs in the heavy chain
Dh region joins with the Jh region DJh region
28
what is the 2nd rearrangement in the heavy chain
Vh rearranged to DJh makes the complete Vh region exon
29
what happens when the complete Vh region exon is created
transcription occurs
30
in the heavy chain what undergoes RNA splicing in heavy chain recombination
joins the assembles V region exon to the C region exon
31
how many segments are there actually in the heavy chain
V - 65 D - 27 J - 6
32
where does recombination occur at
recombination signal sequence
33
structure of RSS's
made up of a heptamer 12 or 23 base pairs nonamer 9 base pairs
34
what are the 23/12 base pairs brought together by
proteins which binds spacer length
35
what is the side-effect of imprecise joining in VDJ recombination
creates lots of diversity
36
what occurs if the V and the J segments have the same orientation
the intervening DNA is cut out into a circle
37
what is occurs if the V and the J segments are in initially opposite directions
complex looping of the DNA is required
38
what is the difference between the light and heavy chain in terms of VDJ recombination
light chain contains only one C region and no D regions
39
what is the 1st rearrangement that occurs in the light chain during VDJ recombination
Vl and Jl rearrangement forms VJl then transcribed
40
what is the 2nd rearrangement in the light chain
brings the V region exon next to the C region exon
41
what are the actual amount of segments in the light chain
V - 30-40 J - 4-5
42
how are immunoglobulin genes organised
3 clusters, each on a separate chromosome 2 light chain loci, each slightly different
43
what does the recombination machinery bind to
both the light chain loci preferentially targets K therefore more K antibodies than L
44
what is combinational diversity
from the different combination of gene segements
45
what is junctional diversity
from the addition of nucleotides when recombination occurs
46
outline how junctional diversity is achieved
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
where is CDR3 located
falls at the V/D/ J segments
48
what happens if an immature B-cell recognises a self-antigen and what does this lead to
its surface IgM will cross link apoptosis
49
epitopes are usually what
long polysaccharides with repeating sugar sequences
50
what do epitopes bind and what does it lead to
IgM and IgD a strong activation signal is generated B-cells release IgM
51
what is linked recognition
antigen-dependent maturation requires T-cell help which recognises the same antigen like 2FA for B-cells
52
outline steps 1/2 T-cell help in antigen dependent B-cell maturation
1 - BCR binds to an antigen 2 - antigen is internalised and presented on MHC class II molecules
53
outline steps 3/4 T-cell help in antigen dependent B-cell maturation
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
what expresses CD40L and what is its function
T-helper cells stimulates B cells to proliferate and become plasma cells
55
function of IL4/5/6
IL4 - drives proliferation IL5/6 - drive plasma cells
56
where are B cells temporarily trapped and why
in the T cell zone to come into contact antigen and T helper cells
57
what is the germinal centre and how long does it take to form
made up of proliferating B cells takes 7-10 days to form after infection
58
what is the mantle zone made up of
resting B cells displaced by activated B cells
59
what do B cells undergo in the germinal centre
somatic hypermutation affinity maturation class switching
60
as B cells multiply, what happens at the V regions of both chains
point mutations occur - on purpose leads to CDR's
61
what is the function of newly generated CDR's from point mutations
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
what is the function of affinity maturation
allows B cells to develop receptors with hugely increased ability to recognise antigens more B cells that are more antigen specific
63
what is AID
cytidine deaminase that introduces nicks in the DNA that are 'repaired' cause of the point mutations
64
what is class switching
changes to the IgG, IgA, or IgE during the immune response after T cell help
65
what is the purpose of class switching
allows a different C region to be used in antibody with a specific antigen binding region
66
what is changed in class switching and why
only the constant region changes - so binds to the same antigen but the outcome of binding is altered
67
when is IgM expressed
before somatic hypermutation
68
features of IgD
expressed upon cell activation is a cell-surface antigen receptor
69
features of IgG
opsonises pathogens for phagocytosis most abundant can cross the placenta monomeric
70
features of IgA
functions on epithelial surfaces - neutralisation mucosal antibody
71
function of IgE
localises to mast cells on the mucosa
72
what antibodies are secreted in neutralisation
IgM - + IgG - ++ IgA - ++
73
what antibodies are secreted for opsonisation
IgM - + IgG - ++ IgA ++
74
what antibodies are secreted for sensitisation for killing by NK cells
IgG
75
what antibodies are released for sensitisation to mast cells
IgG - + IgE - +++
76
what antibodies activate the complement system
IgM - +++ IgG - ++ IgA - +
77
which antibodies are transported across the epithelium
IgM - + IgA +++
78
which antibodies diffuse into extravascular sites
IgG - +++ IgA - ++
79
which antibodies are released in response to a viruses and extra-cellular bacteria (in general)
IgM IgG IgA
80
what is released in response to intracellular bacteria
only T-cells
81
what antibody is released in response to fungi and protozoa
IgG
82
what antibody is released in response to worms
IgE
83
what does Fc bind to
Fc receptors
84
how do phagocytic cells internalise antigens
through Fc receptor binding
85
natural killer cells kill target cells through what
antibody dependent cell mediated cytotoxicity (ADCC)
86
what phagocytic cells do not produce cytokines
naive B cells
87
what do B cells generally produce instead of cytokines and for what
chemokines induce migration of T cells - assist with T cell help