Chad Mosby
Joe McClellan
Cory Moore
Luke Macon
Antibody Final Model Project
The immune system of the human body takes many effective defensive measures
against foreign bodies. Antibodies play a pivotal role in the identification and
elimination of such pathogens. We chose to create - upon Dr. Falvo’s suggestion - a
model of an antibody because we wanted to learn more about its structure and how it
relates to its function.
Antibody Structure:
Antibodies consist of four polypeptides (two heavy chains and two light chains),
which are joined together to form a
symmetrical y-shaped structure. The
light chains (seen on the outsides of
this diagram) are composed of 2
domains of approximately 110 amino
acids each. The heavy chains in the
center are composed of 4 or 5
domains of approximately 110 amino
acids each. Each of these domains
consists of 2 beta pleated sheets
joined by a single disulfide bond.
Both the light and the heavy
chains have a variable domain on the
end (shaded in blue) with three small
hypervariable regions that determine
the shape of the antigen-binding site.
http://www.accessexcellence.org/RC/VL/GG/images/Fig_5.
These hypervariable regions are
25.jpg
short polypeptide sections of 5-10
amino acids that directly contact the
antigen at the antigenic determinant
(what the antibody recognizes and
binds to). The rest of the long and
short chains are constant regions
from antibody to antibody.
Antibodies have the ability to
hinge
at
the disulfide bonds between
Illustration of domains with β sheets from
th
the heavy and light chains in order to
Molecular Biology of the Cell (4 edition)
accommodate the size of the
antigenic determinant. They also are able to hinge at the two disulfide bonds that connect
the 2 heavy chains.
How antibodies are produced:
Antibodies are made by B lymphocytes. B cells begin in the bone marrow as preB cells. Eventually, after rearrangement of genes coding for immunoglobulin, antibodies
are embedded in the cell membrane. The cell is now called a naïve B cell, because it has
not yet interacted with antigen. All of the antibodies on one cell are identical, and all B
Chad Mosby
Joe McClellan
Cory Moore
Luke Macon
cells in the body produce different antibodies by random genetic combination. At least
90% of B cells never interact with antigen and die within several days. When a B cell
does come into contact with antigen, the antigen is brought inside the cell and processed
for presentation to a T cell. When the B cell comes into contact with a T cell specific for
the same antigen, the T cell releases cytokines, which cause the B cell to differentiate.
The T cell cannot detect antigen in its pure form. It must have the antigen
presented to it by an antigen presenting cell such as a macrophage that has ingested a
bacteria. When the antigen is processed by the macrophage, it is broken up and displayed
on the outside by Class II MHC (major histocompatability complex) proteins. Much like
surface antibodies of a naïve B cell, the T cell has antigen receptors on the surface that
are formed through random genetic combination. T cell activation occurs when these
receptors interact with the antigen-MHC Class II molecules. Now the T cell is ready to
interact with B cell.
Activated B cells form plasma cells and memory cells. These new cells may
differ in the class
of antibody that
they produce, but
all will be specific
to the same
antigen. Plasma
cells secrete large
numbers of free
antibodies, which
circulate through
the body. Some
of the B cells
maintain the
IMGT Marie-Paule page
presence of
http://imgt.cines.fr/textes/IMGTeducation/T
surface antibodies,
utorials/IGandBcells/_UK/MolecularGenetic
similar to the
s/angfig5.html
naïve B cells, and
are known as memory cells. The presence of these cells improves immune response the
next time the antigen is detected because they require lower levels of antigen to become
activated.
How antibodies function:
The antibody eliminates pathogens in the body. It does this by binding to sites on
the pathogen known as antigens. The hypervariable regions of the antibody bond with
the antigenic determinant in an interaction that is made more specific by hydrogen bonds,
van der Waals forces, hydrophobic interactions and electrostatic forces. Once an
antibody has attached itself to the antigen, it can eliminate the foreign body in four
different ways.
First, if the foreign body is a virus, the antibody begins the process of
neutralization, during which it blocks viral receptors from binding to their preferred
Chad Mosby
Joe McClellan
Cory Moore
Luke Macon
docking site on a cell. This keeps the virus from injecting its genetic code into cells. The
antibody can also cause agglutination of the foreign bodies, in which the intruders are
clumped together and eaten by phagocytes. Antibodies can also just mark individual cells
for ingestion by phagocytes. Alternatively, the antibody can activate a mechanism for
destruction known as the membrane attack complex.
Nanotechnology application:
One potential use of antibodies in nanotechnology is improving methods of drug
delivery. Antibodies known to target melanoma tumor cells can be combined with
multiple C60 buckyballs in order to deliver multiple drugs simultaneously to the tumor
without having to spread the medication throughout the entirety of the human body.
Multiple buckyballs are used so that a variety of medicines can be delivered, increasing
the chances that the cancer cells are totally eliminated. This specific delivery cuts down
on the harmful side-effects of the medicine used to kill these tumor cells.
In modeling an antibody, we used pipe cleaners to represent the polypeptide
chains. The structure of the antibody includes many distinct shapes and the model
therefore called for a
material that was easy
to manipulate. The
malleability of the pipe
cleaners allowed the
construction and
interconnection of the
beta sheets that
compose the antibody.
This also assisted in
making the
hypervariable regions,
disulfide bonds, and
antigen portions of the
model. Cardboard was
used to create the
antigens, differentiating
the antigens from the
antibody while still
achieving a geometric complement to the hyper variable regions. Twist ties were then
used inside the beta sheets in order to maintain stability.
As we researched and created this antibody model, we discovered that many
systems with many complex components must interact for the immune system to function
properly. This gave us a greater appreciation for the essential service our immune system
provides.