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 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:
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
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
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
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