The actions of antibody are many and varied. Antibodies can
act independently of the rest of the immune system or they can
work to help immune cells and other products recognize a pathogenic
threat and work in cooperation to remove the danger.
/ IgG response to pathogens
When a foreign antigen enters the body and elicits an antibody
response there is a certain set protocol that B cells and antibody
production follows. If the invading pathogen has antibodies that
the body has never seen before, it takes a little time for the B
cells to get their act together. There is a time lag between the
first presentation of the antigen to B cells and their proliferation
and differentiation into antibody producing plasma cells. The time
lag may last several hours to several days depending on what type
of antigen is presented. The first antibody type produced by B cells
is IgM. Once production begins it rises exponentially, rapidly increasing
the responsive antibody concentration in the blood serum.
Several hours after the start of IgM production, IgG producing
B cells swing into action. Eventually the blood serum concentration
of IgG rises higher than IgM levels. IgG is more potent in destroying
pathogens and because of its small size it can penetrate into all
tissues to carry the war to the site of danger. IgM activity is
mainly limited to the blood stream. IgM is therefore the first line
of defense in an antibody response, attempting to keep a lid on
the pathogen invasion until enough IgG antibodies can be made.
Both IgM and IgG antibody continue to be produced for as long
as the antigen is present. Eventually the B cell stimulation tails
off as the amount of antigen present is removed from the body. Remaining
unused antibody is catabolized and broken down. Different antibodies
have different abilities to survive in the body. For example the
half life (time it takes for a concentration of antibody to reduce
by half) of IgG1, IgG2 and IgG4 is 20 days. IgM is less robust with
a half life of 10 days, IgA lasts 6 days with IgD and IgE type antibodies
having a half life of 2 days before being broken down.
Should the same pathogen with the same antigens attempt to re-invade
the body the subsequent antibody production is faster and stronger
than first time around. The B cell system has already seen this
threat before and has learnt what to do. This time the IgG antibody
producing cells proliferate and release IgG just as quickly as the
IgM producing cells. This time around the IgM type antibodies are
virtually superfluous. The antibody production persists for longer
and reaches up to ten times the concentration of antibody produced
in the initial antigenic challenge.
Classic defense against a pathogen involves
antibody binding to the pathogens antigens. This signals the immune
cells that the substrate the antibodies are bound to should be
destroyed. Immune cells will link to the antibodies via Fc receptors.
This receptor linking activates the immune cell into destroying
Use of X ray crystallography has demonstrated the shape and function
of antibody binding sites on the Fab arms of the "Y" shape
molecule. Shape is what defines which antigen shape the antibody
can bind. Actual binding is an active process involving several
chemical and electrical interactions between the antigen and antibody
receptor. Chemical binding involves the linking of oxygen or nitrogen
molecules in the antigen and antibody to a hydrogen atom (usually
taken from water in the vicinity).
Electrical bonding works in two ways. Overall, antibodies are
negatively charged whereas antigens are frequently positively charged.
The electrostatic attraction between the two can help keep them
together. A second and stronger electrical method of binding involves
"Van der Waals" forces. Essentially each atom of a molecule
has a net positive or negative charge depending on how many electrons
it contains. Positive and negative atom charges can provide a quite
strong bond between antibody and antigen.
Finally the strongest form of antigen/antibody bonding is "hydrophobic
bonding". Some parts of molecules don't like water (hydrophobic)
and will physically bond to anything to force water molecules away
from the immediate vicinity. Antibody binding sites have this property.
For all of these attractive forces to work the antigen and antibody
molecule must be close to each other. There must be a pretty good
fit between the shape of the antigen and shape of the antibody receptor
site before the molecules get close enough to each other to form
the bonds. It is possible for several antigens to be very similar
in shape. Perhaps they only have one or two molecules difference
between them. It is possible for an antibody to bind to all of these
antigens but those that don't fit perfectly will have weaker bonding
ability. The reduced bonding strength may not be strong enough to
overcome repulsive forces that are ever present pushing the antibody
and antigen apart.
The ability of an antibody to bind a particular antigen is called
antibody "affinity". An antibody has greater affinity
for an antigen with the right shape to fit its receptors than an
antigen with a looser fit. It is possible to have antibodies produced
against an antigen that have low affinity and other antibodies that
have a high affinity. We often find that when the body is challenged
by a pathogen it has never seen before the antibodies produced have
a slightly loose fit (low affinity) around the pathogens antigens.
If the body is challenged by the same pathogen later in time the
immune system, using its previous experience, produces antibodies
with a better fit (high affinity).
When considering antibody/antigen binding we must also consider
what is called antibody "avidity". Each antibody has at
least two receptor sites (10 receptor sites on an IgM molecule).
Each pathogen may have numerous copies of the same antigen spread
over its surface. So one antibody can bind to several antigens on
the same pathogenic organism. The strength of several bindings between
antigen and antibody is far greater than the sum of the individual
bonds. This is because for the antibody to be separated from the
antigen it has bound all the bonds at all the receptor sites must
be broken simultaneously and that takes a lot of energy. An IgG
antibody for example bound by both its receptor sites to an antigenic
particle has a 1000 fold stronger bond than if it were bound to
two separate antigens.
In all of the above you should see that there is a degree of imperfection
in an antibody's specificity for a particular antigen. It is possible
for two or more antigens to be very similar but not quite the same.
The similarity may be good enough for an antibody to loosely bind
an antigen it was not made for. If the antibody binds to several
of the wrong antigens on the same organism then the strength of
the bonds can be quite strong. This is called "cross-reactivity".
In most instances this is of no lasting significance. A pathogenic
organism can have subtle differences in its surface antigens due
to imperfect manufacture or because of damage. It makes sense to
have a little flexibility in the bind properties of an antibody.
However, sometimes an antibody can cross react with an antigen on
an entirely innocuous structure including our own self antigens.
Only one antigen will fit into an antibody
receptor cup fit absolutely perfectly. Each antibody receptor
might accept other antigens that look similar to the one it was
designed for, but if the fit is not good then most likely the
binding between antibody and antigen will be weak. If it is too
weak the link will probably be broken by heat and fluid motion
around the antibody/antigen.
complexes / antigen precipitation
Immune complexes are a regular feature of infection and/or tissue
damage. Any inflammatory reaction is a destructive process. The
intention of inflammation is to break down bacteria or cells or
whatever the perceived threat is to render it harmless to the body.
This destruction and breakdown of the target creates a lot of debris.
The bacteria or cell fragments have to be removed from the tissue
and blood stream otherwise over time they will increase in concentration
and basically gum up the works. In addition, these fragments may
still be antigenic. For as long as they remain in the system they
have the ability to stimulate the immune system. Permitting these
antigenic fragments to persist in the body could be dangerous as
they will perpetuate the immune response long after the threat has
been destroyed. This prolonged stimulation might result in the immune
system turning on the body and the development of an autoimmune
The immune system likes to keep a clean ship and antibodies help
in the process of mopping up these fragments. Antibodies bind the
fragments together and help precipitate the fragments out of solution.
Binding the fragments together also makes it easier for phagocytes
to latch on to the particles and engulf them. Immune complexes are
removed from the blood primarily by liver Kuppfer cells and also
by phagocytes in the lungs and spleen.
Immune complex formation between antigenic
material (bacteria, viruses, tissue fragments etc.) and antibodies.
Immune complexing pulls small particles out of solution and makes
it easier for phagocyte cells to see the material and engulf it.