Two of the five classes of antibody can
actually polymerize, form polymers.
Those two classes are IgA and IgM.
So you can find immunoglobulins as a single unit if
you like, what immunologists refer to as a monomer.
And IgG, IgD, IgE and IgM when it’s found on the cell
surface acting as the B-cell receptor of B-cells.
And IgA in the blood circulation.
These are all found in
this monomeric form.
However IgA is also very
dominant at mucosal surfaces.
And this so called secretory IgA is two individual units
of IgA linked together by a molecule called the J chain.
There’s also an additional molecule
called secretory component that is
associated with this dimeric secretory
IgA that is present at mucosal surfaces.
The IgM that is found in the circulation, in contrast to
that found acting as the B-cell receptor on the surface
of B-lymphocytes; when IgM is present in the circulation,
five units of IgM link together to form a pentamer.
And again, this J chain molecule, it’s nothing
to do with the J genes that you may have heard
about when we were talking about immunoglobulin
and T-cell receptor gene rearrangement.
This is a completely different thing, it’s a
separate, it’s a protein molecule called J chain.
It joins together individual units
of antibodies when they polymerize.
So for both secretory dimeric IgA and for circulating
pentameric IgM, J chain facilitates that polymerization.
The different antibodies are not all present
in the circulation at the same concentration.
In fact, far from it.
IgM is present in a concentration of around about 45
to 250 milligrams per deciliter (mg/dL) in the adult.
IgG is more dominant.
We have approximately
620 to 1400 mg/dL.
And in fact IgG is the most dominant
class of antibody in the circulation.
Followed by IgA, which is present
at around about 80 to 350 mg/dL.
And these three classes of antibody, the dominant
IgG, second most concentrated IgA and then IgM.
They constitute the vast majority
of antibody in the circulation.
Over 99% of your circulating
antibody is either IgG, IgA or IgM.
Because we have vanishingly small amounts of IgD in the
circulation, less than 8 mg/dL, and miniscule amounts of IgE.
When antibody binds to antigen, it
recognizes particular amino acid
sequences within the antigen, if
the antigen is a protein antigen.
And these areas that are recognized by antibodies on protein,
or indeed on other types of antigen, whether it’s a
nucleic acid antigen or a lipid antigen, the area that is
recognized by the antibody is referred to as the epitope.
And the larger the antigen, the
more epitopes will be present.
So this single antigen may have several different epitopes,
each one of which can be bound by a different antibody.
So let’s just for the sake of argument
say that this antigen is hen egg
lysozyme, an antigen that lots of
immunologists use in experiments.
So it may be that there’ll be one antibody against epitope 1
on the hen egg lysozyme, another against epitope 2 and so on.
So they’re all specific for the same antigen,
but they’re different antibodies and they’re
specific for different areas or different parts
of that antigen; the different epitopes.
The binding of antibody to antigen
involves non-covalent forces.
I’ve already mentioned that the two heavy
chains are linked together by disulfide
bonds, the light chains each one linked
to a heavy chain by disulfide bonds.
So these are covalent bonds,
However the binding of antibody
to antigen is a reversible process
because all of the bonds that are involved are non-covalent.
So amino acids in the Complementarity
Determining Regions interact with
amino acids in the epitope using these
non-covalent reversible forces.
And there are four major forces that are
involved - hydrogen bonding, electrostatic
interactions, Van de Waals interactions
and hydrophobic interactions.
And the overall binding strength that is generated by
these various types of non-covalent bonds results in
the strength of binding of the antibody to the antigen,
and we refer to that as the affinity of the antibody.
However, as we’ve already heard, antibodies
have at least two antigen binding arms.
And in fact if you think about it, in secretory
dimeric IgA there are four antigen binding arms.
And in circulating IgM, there are 10 antigen binding arms,
because it’s five units of antibody linked together.
So the actual total strength of binding depends upon
multivalent interactions that are occurring, and we refer
to this as the functional affinity - the actual affinity
that’s happening in practice, or the avidity of binding.