The structure of Antibody
Immunoglobulin’s are made of 4 polypeptide chains
The light chains and heavy chains are joined together by di-sulphide bonds.
The front portion (forked area) are the part of the Ab that will bind to the
Ag and is called Fragment Ag Binder (FAB)
The tail end can be crystallized using papain so it is called the Fragment
In the experiment using papain the Ab was completely separated into FAB
The Ab could still bind to the Ag, but it did not neutralize the Ag
In another experiment using pepsin still got 2 FAB segments, but each one
had a small fragment of the FC on the end
This allowed the Ab to bind to the Ag and also for the Ag to be neutralized
Therefore, the FAB is important for binding to the Ag and the FC is important for destroying
The FC region allows complement to bind to it for opsonisation
Light chains have 210 amino acids
The Ab has a N terminal that is variable and contains 105 aa and is coded for in genes
The sequence of the Ab binding site is changed by rearranging the aa
This allows Ab’s to change to fit different Ag’s
It also has a C terminal (meaning carboxyl and constant) that is constant with 105 aa
Between the N and C terminals are a diversity and a joining region
V1 V2 V3 Diversity Joining IgG IgM IgD IgE IgA
If you had this Ab at resting stage and had an infection that required IgA it would change becoming
Note that the V region does not change (it could be any of them based on what was needed) but
the diversity and joining regions are always the same and always present.
Class switch is stimulated by constant Ag stimulation of the B cells
Class switch is a process whereby the B cell, as it develops into a plasma cell, can switch the
class (also called isotype) of antibody it produces while retaining the same antigen specificity.
Class switch involves rearrangement of the FC area of the immunoglobulin gene.
Class switch does not occur until after B cell activation and proliferation.
Class switch is under the control of cytokines such as (IL-4, IL-5, IL6, and IFNγ
o The cytokines for this are produced from CD4 T cells.
Since B cells initially express IgM they are initially using the constant (C) heavy chain gene
for IgM (the mu gene).
In class switch to IgG for example the mu gene is spliced out such that the portion of the
gene that defines the variable region of the heavy chain is brought into apposition with the
gamma gene. This results in IgG being produced
The heavy chain determines the class of the antibody (5 possible)
The light chains can be either kappa (κ) or lambda (λ). They cannot be both at the same time,
but must be one or the other.
There are 5 possible classes of antibody (immunoglobulin’s)
o IgG – denoted by gamma (γ) - monomer
o IgM – denoted by meu (μ) - pentamer
o IgA – denoted by alpha (α) – monomer in serum and dimer in secretory form
o IgE – denoted by epsion (ε) - monomer
o IgD – denoted by delta (δ) – monomer
All of the Ig’s have different functions and molecular weights
colonizes in the mucus membranes
the main immunoglobulin found in mucous secretions, including tears, saliva, colostrum,
intestinal juice, vaginal fluid and secretions from the prostate and respiratory epithelium
It is also found in small amounts in the blood
IgA is a poor activator of the complement system, and opsonises only weakly.
Female animals come in contact with the pathogens of its infant by kissing/licking the
infant. This will cause the mother to build up Ab’s (by stimulating B cells) causing a
class switch in Ig’s. The IgA that is produced will pass to the infant through the breast
milk. The IgA will then coat the infants mucosal lining as well. The IgA has no need to
go to the lymph system as it is secreted by getting into the goblet cells.
Makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes
where it is usually co expressed with another cell surface antibody called IgM.
IgD is also produced in a secreted form that is found in very small amounts in blood
IgD's function is to signal when the young B cells in the spleen are ready to be activated.
By being activated, they are ready to take part in the defence of the body in the immune
Originally evolved to be good for worm infestations
Now a common cause of allergies caused by IgE attaching to mast cells where an
allergen would attach resulting in degranulation
Least present Ig
the main antibody involved in primary response is IgM
IgM forms polymers where multiple immunoglobulins are covalently linked together
with disulfide bonds as a pentamer.
Because each monomer has two antigen binding sites, a pentameric IgM has 10 binding
sites. Typically, however, IgM cannot bind 10 antigens at the same time because the large
size of most antigens hinders binding to nearby sites.
Because IgM is a large molecule, it cannot diffuse well
IgM is primarily found in serum; however, because of the J chain, it is also important as a
Due to its polymeric nature, IgM possesses high avidity, and is particularly effective at
It is also the first immunoglobulin expressed in the fetus (around 20 weeks) and also
phylogenetically the earliest antibody to develop
Each IgG has two antigen binding sites.
It is the most abundant immunoglobulin and is approximately equally distributed in blood
and in tissue liquids, constituting 75% of serum immunoglobulins in humans.
IgG molecules are synthesised and secreted by plasma B cells.
IgG antibodies are predominately involved in the secondary antibody response, which
occurs approximately one month following antigen recognition, thus the presence of
specific IgG generally corresponds to maturation of the antibody response.
Active in the blood and tissues
Can activate complement and phagocytosis
Pro-inflammatory cytokines particularly IL-4 and IL-2, have a crucial role in activation
of the IgG antibody response.
This is the only Ig that can pass through the human placenta, thereby providing protection
to the fetus.
Can bind to many kinds of pathogens, for example viruses, bacteria, and fungi, and
protects the body against them by agglutination and immobilization, complement
activation (classical pathway), opsonisation for phagocytosis and neutralization of their
It also plays an important role in Antibody-dependent cell-mediated cytotoxicity(ADCC).
There are four IgG subclasses (IgG1, 2, 3 and 4) in humans, named in order of their
abundance in serum (IgG1 being the most abundant).
o Class 1 good for complement activation, opsonization for phagocytosis, reaches
extra vascular spaces, transfers across the placenta
o Class 2 Same as Class 1 but less efficient
o Class 3 same as class 1 and same efficency
o Class 4 everything but complement activation
Neutralization and Blocking
Antibodies are able to neutralize bacterial toxins – this forms the basis of vaccines against
diseases such as tetnus
The Ig molecule blocking the binding of the toxin to the cell receptor via which it enters and
IgM can prevent the movement of bacteria that use flagellae to move
Good for agglutination bacteria. The clumping of cells such as bacteria or red blood cells in
the presence of an antibody. The antibody or other molecule binds multiple particles and
joins them, creating a large complex.
Phagocytosis and Degranulation
The presence of Ab bound to pathogens extends the recognition of phagocytic cells because
now the cell can recognize the Ab Fc receptors
Eosinophils contain granules with contents that are particularly toxic to some worms
Ab bound to Ag can activate the classical complement pathway, this leads to better
phagocytosis because phagocytes have receptors for the cleavage fragment C3b