Anti-idiotypes and Immunity
Dr. Ziad Jaradat
Anti-idiotypes and Immunity
The immune system of an individual can
make millions of different kinds of
antibodies:
Each antibody can in turn be the target of
other antibodies that recognize its unique
molecular characteristics. By means of
such antibody-antibody reactions the
immune system interacts with itself.
 Networks of reactions seem to modulate the normal
immune response, and disorders of the networks
may underline autoimmune diseases, such as
rheumatoid arthritis, systemic lupus erythematosus
and myasthenia gravis, which stem from an
immunological attack on the body itself.
 These interactions, known as idiotype-anti-idiotype
reactions, can be exploited to manipulate the
immune system.
 The possibility could have profound implications for
the therapy of a spectrum of illnesses ranging from
infections through many kinds of cancer to
autoimmune diseases.
 The basis of each antibody’s specificity resides at
one end of its constituent chains of amino acids.
 There are four such chains in an antibody
molecule: two identical heavy, or long, chains
flanked by two identical light chains, or shorter
segments.
 Figure (1) shows a map of the antibody molecule
including the regions of idiotype, allotype and
isotype.
 An initial antibody (Ab-1) isolated from the
animal’s serum and injected into another
animal, will induced a second antibody (Ab-2).
The Ab-2 bound only to the Ab-1 and not to
other antibodies against which it was tested.
It could therefore be said to recognize the
primary antibody’s individuality.
Oudin referred to the unique antigenic
determinants on the Ab-1 as its idiotype
For the Ab-2 produced in response to the
idiotype he coined the term anti-idiotype.
Other work showed that the immune
system can make various kinds of
antibodies in response to an Ab- 1.
Some of them bind not only to the Ab-1 that
induced them but also to other antibodies
with the same class.
Presumably those second antibodies, which
are known as anti-isotypes recognize
antigenic determinants in the constant
regions of the heavy and light chains of the
same class of antibodies.
Another set of antibodies, called antiallotypes, react with every antibody made by
the individual from which the Ab-1 was
taken, although not necessarily with
antibodies from other individuals.
An anti-idiotype, in contrast, was defined as
an antibody that is able to react only with the
Ab-1 elicited by a single antigen.
The idiotype therefore, must lie in the variable
region of the antibody.
Example of production and purification
of the anti-idiotypic antibodies
To produce an antibody against hepatitis B
viral antigen
A rabbit was injected with purified antigen
from HB virus
Collect the serum after several injections and
purify the antibodies against he HB virus.
This antibody is designated as Ab-1.
Inject purified Ab-1 in goat
The serum obtained from the goat will
contain:
preexisting antibodies (none specific)
contains anti-idiotypic antibodies
contains anti-isotypic antibodies
contains anti-allotypic antibodies
Purification and absorption of the antibodies
One column has antibodies that bind both
allotypic and isotypic antibodies but not the
idiotypic antibodies and the preexisting
antibodies
Column 2 has antibodies that bound the antiidiotypic antibodies so when the serum passed
through it captures the anti-idiotypic antibodies
and let the preexisting antibodies pass through.
Column 2 then flushed with a buffer that elutes
the pure form of anti-idiotypic antibodies.
 These anti-idiotypic antibodies mimic the
original antigen therefore, they are called
surrogate antigens.
 This process is depicted in the following
diagram.
Types of anti-idiotypic antibodies
Ab2α; are set of antibodies that idiotopes
distinct from the antigen binding site of Ab1. The binding of these antibodies to Ab1
does not interfere with the antigen binding
capacity of Ab1.
Ab2 β; carries an internal image of the
nominal antigen. They constitute about only
15-20 % of the total Ab2. They interfere
with binding of the Ag to the Ab1(complete
inhibition) . They bear an internal image of
the antigen.
Ab2 γ; like the Ab2 β recognizes epitopes
within the nominal antigen binding site and
can inhibit the binding of Ag to Ab1 but do not
bear an internal image of the antigen, thus
they partially blocks binding of Ag to Ab1.
Anti-idiotypic vaccines
EXAMPLE OF AN EXPERIMENT
human antibody against HB antigen is
injected into a rabbit that makes Ab-2.
Ab-2 is injected into a mouse or a chimp to
make Ab3.
Ab-2 is similar in shape to the antigen
Ab-3 is similar in specificity to Ab1
Now Ab-3 was able to protect the chimp
against a real infection of HB
Advantages of Anti-idiotypic
antibodies
Anti-idiotypic antibodies offer certain
advantages over the conventional vaccines;
Ids would eliminate the complications of
using killed, attenuated or subunit vaccines
thus eliminates the dangers of using these
pathogens
A major advantage is their ability to trigger B
and T cell immunity. They induce the
generation of the T-helper memory cells
which results in long lasting immunity. This
property may confer immunity on neonates
who do not respond to conventional
immunotherapy.
One of the most advantages is the use of
anti-idiotypic antibodies is mapping antigenic
sites or epitopes involved in immune
recognition.
Anti-idiotypic antibodies that could prime the
host for a desired immune response could be
sequenced and computer models could be
generated to predict antibody binding sites.
These data could be used to predict
immunodominant epitopes on the organism
or tumor and lead to the synthesis of better
vaccines.
This can be useful in identification of cell
surface receptors.
Another method, the idiotypic antibodies
can be easily labeled with FITC or electron
dens particles so that its target on the cell
surface will be identifiable under light
microscope.
Disadvantages
Repeated immunization of humans with
heterologous serum proteins lead to the
development of serum sickness
Vaccination with anti-idiotypic antibodies may
not confer a complete protection and may
require subsequent exposure to an antigen.
Thank You