Where
does the name g-globulin come from?
Antibodies are secreted and
they also exist as the B-cell receptor (BCR)
on the surface of the
B-cell.
The
B-cell receptor also has other proteins associated with it:
Antibodies have two
fundamental characteristics:
Specificity Ð the ability to bind to epitopes. One B-cell will
make only one specificity of antibodies.
That is, they will bind to one epitope.
The
clone of B-cells that derive from one original B-cell will all make the same
specificity.
Biologic
Activity Ð the ability to trigger
protective physiological activities usually after binding to antigen. This would include:
á
opsonization,
á
activation of
complement,
á
clearance of antigen,
á
allergic responses,
á
neutralize toxins,
á
neutralize viruses and
other activities.
There
are different groups or classes of
antibodies. These groups differ in
structure and in biological activity. The class of antibody is also called the isotype of the antibody.
There
are 5 isotypes or classes of antibodies in humans:
Please look at the figure on
page 40 (Fig 4.1).
This
figure describes the electrophoresis
of normal serum and compares it to the electrophoretic pattern of serum from a myeloma patient.
Myeloma or multiple myeloma is a cancer of plasma cells.
á
Such cancers typically
result in very high serum concentrations of antibody.
á
The great excess of
antibody will be of one specificity and of one class (or isotype).
o
This is because most of
the antibody is derived from the cancer cells.
o
This antibody excess is
monoclonal.
á
These patients also make
an excess of free antibody L-chains.
o
These excess L-chains
get filtered out by the kidneys and excreted in the urine.
o
These L-chains in the
urine are called Bence-Jones proteins.
Study
Fig. 4.2 on page 41:
á Describe the protein fragments that result from the papain digestion of the antibody monomer.
á
Describe the protein
fragments that result from the pepsin digestion of the antibody monomer.
There
are 5 different classes of antibody and these classes are defined by the class
of Heavy Chain or H-chain:
IgM -- µ chain Ð 5 domains -- mu
IgG
-- g
chain Ð 4 domains --gamma
IgA
-- a
chain Ð 4 domains -- alpha
IgE
-- e
chain Ð 5 domains --epsilon
IgD -- ¶ chain Ð 4 domains -- delta
There
are 2 classes of Light Chains (L-chain):
l chain Ð 2 domains Ð lambda
k chain Ð 2 domains Ð kappa
1. All chains, H or L, have an N-terminal variable region domain
2. One antibody molecule will have identical H-chains
3.
One antibody molecule will have identical L-chains
4.
All the antibody molecules made by one B-cell will have the same specificity
5.
All the antibody molecules made by a clone of B-cells will have the same
specificity
6.
All the antibody molecules by a clone of B-cells will have identical L-chains.
7.
A clone of B cells can make several different antibody classes:
This
means that the clone will make different H-chain classes, butÉ.
These
different classes will have the same specificity! (see #4 and #5 above).
This
would have to mean that all the H-chain classes made by the clone would have to
have identical V-regions.
Of
course, all the antibody molecules made by the clone, regardless of class,
would have identical L-chains. (See
#6 above).
Structural features of the
Antibody Classes:
Please look over Fig 4.9 on page 47 to compare the structures of the 5 human antibody classes.
Also,
Table 4.2 on page 45 and compare the molecular weights and the protein
subunits. Does the table agree
with the figure?
Biological Properties of
Antibody Classes:
IgG
á
Most abundant of all the
Ig classes
á
Longest half-life of all
the Ig classes
á
Can get recycled back
out of antigen presenting cells via the FcRp or the Brambell receptor (see fig.
4.10).
á
Agglutinates particulate
antigens
á
Precipitates soluble
antigens
á
This is the only
antibody class that crosses the placenta Ð FcRn receptor
o
Neonates also express
FcRn on their intestinal cells for about the first 2 weeks of life
á
Opsonizes antigen Ð
Phagocytic cells have FcR, thus they can more easily ingest antigens if those
antigens are coated with IgG. (See fig 4.11).
á
Again, by virtue of FcR
on Natural Killer cells, these NK cells kill invading cells that are coated
with antibody.
á
IgG that is bound to
cells or IgG that is aggregated in antigen-antibody complexes can activate
complement.
á
IgG is good at
neutralizing toxin
á
IgG can interfere with
bacterial virulence features such as motility and adherence to tissues
á
IgG can block virus
ability to adhere to target cells
á
IgG is the main antibody
found in the secondary immune response
IgM
á
IgM monomer is the
B-cell receptor of the mature B-cell
á
IgM is the first
antibody made in an immune response Ð about 7 to 10 days after initial exposure
á
IgM is the first
antibody made in life Ð about 5 months in utero
á
IgM is the most
primitive antibody class Ð found even in primitive vertebrates.
á
IgM is the antibody made
to T-independent antigens Ð polysaccharides
á
IgM is a very good
agglutinating antibody
á
Natural
isohemagglutinins are IgM class
á
IgM attached to antigen
is a very good activator of complement
á
IgM does not cross the
placenta
IgA
á
IgA is the secretory
antibody Ð found in all secretions including colostrum and milk.
á
IgA is particularly
important for protection against respiratory and gastrointestinal infectious
agents.
á
IgA is important for
passively acquired immunity of nursing baby.
á
IgA makes lysozyme work
better Ð especially against gram-negative bacteria
á
IgA neutralizes virus
á
IgA is transported
across membranes via the poly-Ig receptor
IgE
á
IgE is made in response
to parasitic worms. When bound to
the parasite, it triggers a very strong inflammatory response to the worms.
á
IgE is the antibody that
triggers allergy
á
IgE binds to Fce receptors on the surface of mast cells