Let’s now turn to what
antibodies actually do.
We’ve looked a little bit at their structure, but how do
they actually function to protect us from all the
different nasty pathogens that we’re encountering
all the time - bacteria, viruses, fungi, parasites.
Well antibody can actually function totally alone, just
work completely by itself to combat pathogenic situations.
So for example, it can bind to bacterial
toxins and neutralize those toxins.
Stop those toxins poisoning our cells.
It can block viruses binding
to their cellular receptors.
In order to enter a cell, a virus has to
bind to the surface of one of our cells.
If an antibody gets in the
way, the virus can’t bind.
Or antibodies can block adherence
of bacteria to mucosal surfaces.
And secretory IgA is
really good at doing that.
So these are three examples of antibody not needing
to draw on help from other parts of the immune system.
They can do all this stuff
completely on their own.
But most times, antibody acts as a bridge between the
antigen and other components of the immune system.
So let us look at the
ways in which this occurs.
So looking at the variety of ways in which
antibodies recruit other components of the immune
response, one important way is using red blood cells
to facilitate the clearance of immune complexes.
We tend to think of red blood cells
as transporting oxygen around
the body and really perhaps not much
to do with the immune response.
But like most cells in the body, red
blood cells have more than one function.
And they have on their cell
surface, complement receptors.
And this means they can pick up immune complexes
of antigen and antibody and complement.
And they bind those complexes and take the immune complexes to
places like the liver and the spleen where there are lots of
phagocytic macrophages that can take up the immune complexes and
destroy the pathogen or substances within the immune complex.
And the IgM and IgG class of antibody
are really good at doing this
because they can activate complement via the classical pathway.
Microorganisms often need to be opsonized, coated
with substances that maximize their phagocytic uptake.
And antibodies are good at opsonizing
microorganisms for phagocytosis.
And the IgG class of antibody
is really good at doing that.
A third mechanism, where antibodies function
to link other parts of the immune response
into the protective activity, is
antibody-dependant cellular cytotoxicity - ADCC.
This relies upon a cell
having two features.
Firstly, it needs to have an Fc receptor, and secondly,
it needs to be able to produce toxic molecules.
And in fact most cells in the immune system have both
Fc receptors, and are able to produce toxic molecules.
So, most cells in the immune response
can actually participate in ADCC.
With regards to the class of antibody that is best mediating
this process, IgG again is really good at doing this.
And the result will be that the
cell participating in this process
will release toxic molecules that
will destroy the coated organism.
The generation of a membrane attack complex of complement
is an important mechanism for destruction of microorganisms.
And this involves activation of
the complement system by antibody.
And the two class of antibody that are good at
doing this is the IgM and IgG antibody classes.
And this will lead to the generation of a membrane attack
complex, consisting of complement component C5b, C6, C7, C8, C9.
And this will lead to
the death of the cell.
And then finally, mast cell degranulation is an
important mechanism for dealing with certain parasites.
And the IgE class of antibody is specialized
for carrying out this particular function.
So you see, we have a range of different antibody
classes, and they can participate in a variety of ways
to recruit other cellular or molecular components of
the immune response to help protect against pathogens.
Looking now at the individual antibody classes and
their specialization for different functions, there’s
a reason why we have five different classes, because
to some extent they have specialized functions.
There is a certain overlap
in their functions.
But broadly speaking, IgM facilitates the
recognition of antigen by B-cells because
it acts as the B-cell receptor together
with IgD on the surface of naïve B-cells.
The secreted version of IgM is
mainly present in the circulation.
We saw that it’s a pentamer, five
units of antibody linked together.
That makes it a very
large antibody molecule.
So it can’t easily get out of the
circulation and into the tissues.
But it’s present mostly in the circulation where it is the
first antibody class that is produced in adaptive responses.
So those naïve B-cells will go on, and
before class switching produce lots of IgM.
It’s good at activating complement as
we’ve already heard, and it can also
agglutinate bacteria together, because
it’s got 10 antigen binding arms.
It’s a pentamer, so it’s able
to link together microorganisms.
This is a very good way, this agglutination of microorganisms
is a very good way of combating bacterial infections.
IgG is the most abundant
antibody in the circulation.
It can activate complement, it can
enhance phagocytosis by opsonization.
It can participate in antibody dependant
cellular cytotoxicity, is able to directly
neutralize some pathogens, and uniquely amongst
the five classes, it can cross the placenta.
It’s very important in protecting
the fetus from infections.
The mom will pass IgG against
pathogens she’s encountering.
She’ll pass it across the placenta, and the baby
will benefit enormously from this, because at the
time we’re born, our B-cells are only just
beginning to be able to make their own antibody.
So this antibody coming from
the mom is very important.
And it’s only the IgG class that
is able to cross the placenta.
The secretory form of IgA prevents
colonization at mucosal surfaces.
IgD acts together with IgM as the
B-cell receptor on naïve B-cells.
And IgE in the presence of antigen triggers the release
of inflammatory mediators from mast cells and basophils.
So you see, we have five different
classes of antibody because at least
to some extent, they’re specialized
to carry out different activities.
Although there is a certain overlap.
For example, both IgM and IgG can activate
the classical pathway of complement.