III - B cells Flashcards
what occurs to an activated B cell
becomes either a memory or plasma cell
feature of a memory cell
has a long lifespan
has the same BCR as parent cell
feature of plasma cell
live for only a few days
secrete 2000 antibodies per/s
what is hyper IgM syndrome
primary immunodeficiency in which patients patients only express the 1st antibody type -
IgM
what is the BCR
a membrane bound antibody
what is the structure of an antibody
2 light chains - 25kDa
2 heavy chains - 50kDa
variable region
constant region
where does the antigen bind to an antibody
the variable region
what does the constant region possess
the effector function activity
how is the isotype of an antibody determined
the carboxy terminus of the heavy chain
what is a CDR
a complimentary determining region
where are CDR1/2
they are where the V gene segments are located
what is the unique feature of CDR3
it is the most variable - formed by the heavy chain
what does the periphery regard to
outside the lymphoid organs
what is the earliest class of antibody and what is expressed next
IgM
IgD
what antibodies are made in response to challenges in the periphery
IgA
IgG
IgE
where are early B-cells located
in bone marrow
where is IgM expressed in the B-cell in bone marrow
on the cell surface
how are B-cell receptors rearranged
as in T-cells
where do cells move in the B-cell maturation process
to the spleen
where is IgD expressed after B-cells move to the spleen what is it independent of
on the cell surface
independent of antigens
how does maturation begin
in an antigen-dependent manner
what are essential to the survival of early B-cells in bone marrow
stromal cells in the bone
what is the function of VCAM-1 on stromal cells and what does it convert an early lymphoid cell into
binds VLA-4 on the B-cell
early pro-B-cell
function of SCF from the stromal cells and what does it convert an early pro-B-cell into
binds cKit on the B-cell
late pro-B-cell
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
in VJD recombination - heavy chain, what is the purpose of the leader sequence
takes the protein into the cells secretory pathway to be cleaved
what is the 1st rearrangement that occurs in the heavy chain
Dh region joins with the Jh region
DJh region
what is the 2nd rearrangement in the heavy chain
Vh rearranged to DJh
makes the complete Vh region exon
what happens when the complete Vh region exon is created
transcription occurs
in the heavy chain what undergoes RNA splicing in heavy chain recombination
joins the assembles V region exon to the C region exon
how many segments are there actually in the heavy chain
V - 65
D - 27
J - 6
where does recombination occur at
recombination signal sequence
structure of RSS’s
made up of a heptamer 12 or 23 base pairs
nonamer 9 base pairs
what are the 23/12 base pairs brought together by
proteins which binds spacer length
what is the side-effect of imprecise joining in VDJ recombination
creates lots of diversity
what occurs if the V and the J segments have the same orientation
the intervening DNA is cut out into a circle
what is occurs if the V and the J segments are in initially opposite directions
complex looping of the DNA is required
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
what is the 1st rearrangement that occurs in the light chain during VDJ recombination
Vl and Jl rearrangement
forms VJl
then transcribed
what is the 2nd rearrangement in the light chain
brings the V region exon next to the C region exon
what are the actual amount of segments in the light chain
V - 30-40
J - 4-5
how are immunoglobulin genes organised
3 clusters, each on a separate chromosome
2 light chain loci, each slightly different
what does the recombination machinery bind to
both the light chain loci
preferentially targets K
therefore more K antibodies than L
what is combinational diversity
from the different combination of gene segements
what is junctional diversity
from the addition of nucleotides when recombination occurs
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
where is CDR3 located
falls at the V/D/ J segments
what happens if an immature B-cell recognises a self-antigen and what does this lead to
its surface IgM will cross link
apoptosis
epitopes are usually what
long polysaccharides with repeating sugar sequences
what do epitopes bind and what does it lead to
IgM and IgD
a strong activation signal is generated
B-cells release IgM
what is linked recognition
antigen-dependent maturation
requires T-cell help which recognises the same antigen
like 2FA for B-cells
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
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
what expresses CD40L and what is its function
T-helper cells
stimulates B cells to proliferate and become plasma cells
function of IL4/5/6
IL4 - drives proliferation
IL5/6 - drive plasma cells
where are B cells temporarily trapped and why
in the T cell zone
to come into contact antigen and T helper cells
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
what is the mantle zone made up of
resting B cells displaced by activated B cells
what do B cells undergo in the germinal centre
somatic hypermutation
affinity maturation
class switching
as B cells multiply, what happens at the V regions of both chains
point mutations occur - on purpose
leads to CDR’s
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
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
what is AID
cytidine deaminase that introduces nicks in the DNA that are ‘repaired’
cause of the point mutations
what is class switching
changes to the IgG, IgA, or IgE during the immune response after T cell help
what is the purpose of class switching
allows a different C region to be used in antibody with a specific antigen binding region
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
when is IgM expressed
before somatic hypermutation
features of IgD
expressed upon cell activation
is a cell-surface antigen receptor
features of IgG
opsonises pathogens for phagocytosis
most abundant
can cross the placenta
monomeric
features of IgA
functions on epithelial surfaces - neutralisation
mucosal antibody
function of IgE
localises to mast cells on the mucosa
what antibodies are secreted in neutralisation
IgM - +
IgG - ++
IgA - ++
what antibodies are secreted for opsonisation
IgM - +
IgG - ++
IgA ++
what antibodies are secreted for sensitisation for killing by NK cells
IgG
what antibodies are released for sensitisation to mast cells
IgG - +
IgE - +++
what antibodies activate the complement system
IgM - +++
IgG - ++
IgA - +
which antibodies are transported across the epithelium
IgM - +
IgA +++
which antibodies diffuse into extravascular sites
IgG - +++
IgA - ++
which antibodies are released in response to a viruses and extra-cellular bacteria (in general)
IgM
IgG
IgA
what is released in response to intracellular bacteria
only T-cells
what antibody is released in response to fungi and protozoa
IgG
what antibody is released in response to worms
IgE
what does Fc bind to
Fc receptors
how do phagocytic cells internalise antigens
through Fc receptor binding
natural killer cells kill target cells through what
antibody dependent cell mediated cytotoxicity
(ADCC)
what phagocytic cells do not produce cytokines
naive B cells
what do B cells generally produce instead of cytokines and for what
chemokines
induce migration of T cells - assist with T cell help
