MEACHANISM OF ANTIBODY FORMATION

1. ERLICH SIDE CHAIN THEORY (1897)

Concept
o Ehrlich argued that all cells have a wide variety
of special receptors that he called side-chains. He
thought that these receptors worked like
gatekeepers or locks for the cell. Each
receptor/side-chain had a unique structure, and
only substances matching this structure were
allowed to enter the cell
o The side-chain receptors primary function was
to absorb nutrients for the cell. Unfortunately,
the receptors also allowed many toxic substances
to enter.
o According to Ehrlich, the body defended itself
against these toxins in the following way: When
a cell was attacked by a toxin, it started to
produce excess side-chains matching the toxin.
These excess side-chains then were released,
flooding the body and neutralizing free toxins by
attaching to them. The toxin was wiped out and
remaining healthy cells protected.

Erroneous in the theory
o According to Burdett: chemical Ag-Ab have also
physical nature or colloidal nature
o According to Arkkevius and Madsen: it should
follow the law of mass of action where in Ag-Ab
are reversible
o According to clonal selection and theory of
burnett: the surface receptors have only single
specificity
2. TEMPLATE LENDERBERG THEORY (1930)
Ag introduce new information to Ab producing cell
and then instruct to copy complementary form
Ag serves as the template/ mold
The specificity of Ab is determine by molding of
peptide chain around Antigenic determinant
During embryonic development, they appear to be
subpopulation or closed virgin lymphocytes each
lymphocyte have the capacity to recognize and
respond to one antigenic substance or closely related
group of antibody. This capacity is inherent to cell
even before the Ag is encountered. It is inherent
because of genetic properties which pass from the
parent to ..
Self recognition developed when any of lymphocyte
complex with self component or even foreign Ag
substance present during embryonic development or
eliminated after the period of self recognition
When an Ag enters the body, it selects lymphocyte
that would provide best fit with surface receptor for it
to and able to bind with it. The cell with bound Ag
will stimulated to bind and form a clone of cells that
will produce Ab specific to the Ag.

3. CLONAL SELECTION OF BURNETT (1959)
Most currently acceptable and useful theory of antibody
production which can be extended to explain specific
immune tolerance and the maturation of the immune
system itself. It appears that subpopulation (clones) of
virgin lymphocytes are generated during embryological
development. Each lymphocyte has the capacity to
recognize and respond to a different antigenic
determinant

ANTIBODY DIVERSITY
Isotype- different of Ig classes
Allotype- unique antigenic specifities
Idiotype- found at the constant domain of the Ig classes
- unique determinant group found on the
variable domain
- associated with the Ag binding capacity of the
Ab molecule
- Amino acids provide uniqueness and
specificity to the Ab molecule

GENE ORGANIZATION
Part of the variability of Ig structure is produced from
the interaction of individual chain
o Heavy chain- C14
o Lambda- C22
o Kappa- C2
There are different genes that code for the different
amino acid in the different part of the polypeptide chain

HISTOBACKGROUND
Each immune system makes over 1 billion different Ab
proteins
1950s central dogma stated DNA to RNA to protein
One gene for each protein
Required millions of genes just for the immune system
Does not seem possible, but most scientists thought it
might be
Today we know the human genome is less than 30,000
genes

GERM LINE VS. SOMATIC VARIATION THEORIES
GERM LINE
o Stated that each Ab had its own gene.. nothing
special, but required billions of genes to account
for it of Ab
SOMATIC VARIATION
o Some mutation and recombination created vast
number of genes for Ab formation













B-LYMPHOCYTE DEVELOPMENT



PREYER AND BENNETT
In 1955, proposed radical theory to account for diversity
of Ab
Each of Ab was coded for by 2 separate genes
One for the variable region
One for the constant region
Combined at the DNA level and expressed single mRNA
Suggested 1000s of variable region genes and only one
constant region gene
Most biomedical scientists did not like this idea of
rejected it

TONEGAWAS DEMONSTRATION
1976- used restriction enzymes and DNA probes to show
the germ cell DNA contained several smaller DNA
segments compared to DNA segments compared to DNA
taken from developed lymphocytes


MULTIGENE ORGANIZATION OF Ig GENES