B & I - Adaptive Immunity Flashcards
does adaptive immunity have memory
yes
the _____ response is stronger and more rapid than the _____ response
secondary, primary
the affinity of B cells towards antigen (increases/decreases? how/when)
increases with time and persistence of antigen
you are born with a massive repertoire of?
B and T lymphocytes
what does each lymphocyte represent
a different antigen specificity randomly produced by rearrangement of the genes coding for the antigen receptors
what was adaptive immunity first observed in
jawless fish
adaptive immunity relies on?
the phenomenon of gene rearrangment or recombination - the only genetic locus capable of this
what is the transposase
the enzyme that operates on the transposon
the ancient transposases in your genome are called?
RAG1 and RAG2 (Recombination Activation Genes)
what does RS stand for
Recognition sequences (RS)
where are RS located
at the ends of all the Ig and TcR gene segments
what is RS the substrate for
RAG1 and RAG2 directed recombination
what is identical in all species that possess adaptive immunity
the recognition sequences and RAG1 and RAG2
what does adaptive immunity entail
recognition of traits specific to particular pathogens, using a vast array of receptors
what is included in the humoral response of adaptive immunity
antibodies defend against infection in body fluids
is adaptive immunity rapid or slow response
slow response
what is included in the cell-mediated response of adaptive immunity
cytotoxic cells defend against infection in body cells
what are antibodies made of
repeated Ig domains
where are Ig domains found
in hundreds of different proteins
the Ig protein domain fold is called a
B-barrel (of ~110 amino acids)
what are two anti-parallel B-pleated sheets joined in the middle by
disulphide bond
the loops at the ends of the strands are not constrained - what does this mean
they can vary their amino acid sequences without affecting the stability of the fold
what does the 1st immunisation with antigen result in
a rise in antigen specific low affinity IgM in blood
what are the 2nd and 3rd immunisations called
boosts
what do 2nd and 3rd immunisations (boosts) do
generate a rapid and intense burst of antigen specific high affinity IgG in blood
what are the best vaccines
inactive variants of bacteria toxins that rapidly produce high affinity neutralising IgG that binds to the toxin before it binds to their target receptor
where do B cells begin
in the bone marrow
where do B cells mature
in secondary lymphatic organs such as the spleen and lymph nodes
what do B cells produce and what do they form
antibodies and form the humoral (soluble) arm of the adaptive response
what is the B cell antigen receptor
a membrane bound IgM molecule
what is the B cell receptor associated with
associated with intracellular molecules that transmit an activation signal via phosphorylation
what do T lymphocytes begin as and where do they mature (and what do they mature into) and what do they provide
immature lymphocytes that home the Thymus, where they mature into functional T cells and provide cellular adaptive immunity
what is the antigen receptor on T lymphocytes called
the T cell receptor (TcR)
what is TcR
an immunoglobulin like surface molecule coded for by a separate gene locus
what is TcR associated with and give examples of the two most important ones and what do they do
a number of surface molecules and two important ones are CD4 and CD8 that distinguish two functionally different types of T lymphocytes
what does the antibody molecule consist of
4 protein chains that are all made up of repeating Ig domains
What are they different types of chains and how many domains are there in each
two domains in light chains and 4-5 domains in heavy chains
1H chain is disulphide linked to?
1 L chain
2H chains are ?
disulphide linked
the Y shaped antibody has two flexible arms - what is located at the top of the two arms and where are these formed
antigen binding sites which are formed from the N terminal domains of the L and H chains
the effector region is _________ (invariant/variant) and is bound by __________ and __________
invariant, Fc receptors, complement component C1
what two parts is the antibody split into
antigen binding and effector
What is the default antibody made by all immature B cells
IgM
When B cell encounters antigen and activates, it switches to use the ___ _____ to produce an ___ molecule
Y gene, IgG
what is the rarest class of Ig
IgE
what does IgE cause
atopic allergy
what forms does IgM come in
membrane bound (monomer) and soluble (pentamer) form
what is the membrane form
the B-cell receptor
how many antigen binding sites does the soluble form have
10 antigen binding sites
IgM reacts strongly to surfaces such as microbes through ___________
avidity binding
IgM is good at fixing complement with…
complement with 5 Fc regions that bind complement component C1
when is there affinity
when the sum of the attractive molecular forces at two surfaces exceeds the repulsive forces, there is affinity
(attractive > repulsive)
the higher the affinity… (relative to association and dissociation)
the fewer molecules it takes per unit volume to associate and to dissociate slowly
what does avidity result from
multiple affinity contacts
in avidity, the strength of binding.. (relative to affinity)
can be orders of magnitude higher than the individual affinities
antibodies have two identical antigen binding sites so they are
bivalent
when they bind to a surface using both arms, the binding is governed by
avidity - this is much stronger than the affinity of each individual arm
soluble IgM molecules are pentameric (5 molecules chained together) and thus
exhibit high avidity binding (about 7 orders of magnitude higher than the individual affinity reactions of each site)
IgM is ___ affinity, ___ avidity molecules.
low, high
what do these form (primary surveillance..)
the primary surveillance antibody that initially detect infections
Ig molecules have different functions depending on the
H chain
Naive B cells used the __ gene first resulting in a ______ ______ ___ _________ - this is the B cell antigen receptor
1) u gene
2) membrane bound IgM molecule
after activation, what does the B cell switch to using?
a different heavy chain gene - typically Y which produced IgG
what is the most abundant antibody in serum
IgG
which of the Ig activate complement
IgG and IgM
which of the Ig is secreted at mucosal surfaces
IgA
which of the Ig is involved in Placental transfer - foetal immunity
IgG
which of the Ig has high affinity receptor on mast cells
IgE
which of the Ig have a membrane bound form
IgM and IgD
Ig in order from most abundant in serum to least abundant
IgG > IgA > IgM > IgD > IgE
why can an antibody form complementarity to virtually anything?
because the potential amino acid diversity at the antigen binding site is vast
what is complementarity
the measure of how well two molecules interact with each other
antibody forms complementarity with an antigen surface if?
the sum of the attractive forces exceeds the sum of the repulsive forces
(affinity)
what is the antigen binding site of Ig and TcR formed from
the 6 protein loop regions that connect the B strands in the Ig variable domain
The loop regions are called _________________ __________ ______ and contain massive amino acid diversity caused through the….
complementarity determining regions
rearrangement and imprecise joining of germline gene segments in the Ig and TcR locus
where is amino acid variation found
in CDR, specifically the 3 loops that connect the strands in the 1st domains of the H and L chains
3 loops from Vh and Vl juxtapose in the folded protein to form ?
a roughly rectangular surface
how many identical antigen binding sites are there
2
what are germ-line genes segmented into?
clusters called Variable, Diversity, Joining and Constant regions
which chain has no D segments
light chain
what are RAG1 and RAG2 responsible for and what are they active in
responsible for rearrangement and are only active in B and T lymphocytes
during recombination, what segments join to what and what happens to intervening DNA
D to J and then V to D. Intervening DNA is lost.
how does VDJ joining create variation
joining is very imprecise so base pairs are changed during repair, this leads to huge variation
what does the VDJ region code for
CDR3
the light chain also rearranges, but since there are no D segments, what segments join?
V joins to J
imprecise joining results in massive amino acid diversity in the
CDR3 loop on the antigen receptor
immune system doesn’t know what immune repertoire is required prior to birth, so person is born with millions of different B cell antigen specificities as a result of?
random rearrangement of the Ig locus before birth
when are individual B cell clones selected to mature
when they encounter antigen within germinal centres in lymph nodes
where does clonal selection take place
within a B cell follicles in your lymph nodes
one B cell =
one antigen specificity
a massive repertoire of naive B cells is generated…
stochastically before birth each with a unique B cell receptor
where do B cells encounter antigen
in lymph nodes
antigen expands a small number of B cell clones with ?
receptors that weakly bind the antigen
what does somatic hypermutation of the Ig gene result in
some clones with higher antigen receptor affinity
after successive rounds of this, what happens to the mature B cell
it becomes a plasma cell which secretes soluble Ig
some B cells reside in lymph nodes as long-term _______ ____.
memory cells
what is the fundamental mechanism behind vaccination
affinity maturation
MAIN POINT: you have a vast immune B cell repertoire that is
generated stochastically before birth
MAIN POINT: The Ig and TcR gene loci are segmented into
VDJ regions
MAIN POINT: what does genetic recombination and imprecise joining of gene segments results in
huge diversity in the regions that constitute the antigen binding surface of antibodies and T cell receptors
MAIN POINT: what does each naive B cell represent
a unique antigen specificity
MAIN POINT: antigen drives _______ _________ and ______ in the ____ ____ follicles.
clonal selection and expansion
lymph nodes
MAIN POINT: persistent antigen and somatic hypermutation results in
some B cells with increased affinity towards antigen
MAIN POINT: some become antibody secreting…
plasma cells
MAIN POINT: other cells become long-lived ______ cell that reside in ______ tissue ready to respond rapidly to re-challenge
memory
lymphoid
MAIN POINT: why does immunisation work
affinity maturation
