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2019/2020 Second Semester

Module 3_Lecture 3: Immunoglobulins- 01/05/2020 (2hours)
Lecturer: Dr. O. Oduwole

• Structure and function of antibodies,

We are confronted with different infectious agents on a daily basis, as a result, immune
responses come in a number of ways and are targeted towards the nature of the pathogen that
provoked the response in the first place.
Microorganisms are sometimes able to resist phagocytosis. If small amounts of antibody are
added the phagocyte springs into action. It does so through the recognition of two or more
antibody molecules bound to the microbe, using specialized Fc receptors on the cell surface
of the phagocyte

As mentioned earlier, antibody molecules carry out two principal functions in immune
defense. The first function is to recognize and bind to foreign material (antigen). This
generally means binding to molecular structures on the surface of the foreign material
(antigenic determinants) that differ from molecular structures made by the cells of the host.
These antigenic determinants are usually expressed in multiple copies on the foreign
material, such as proteins or carbohydrates on a bacterial cell surface or envelope spikes on
the surface of a virus. Antibodies of a single host can recognize a huge variety of different
molecular structures – a human is capable of producing antibodies against billions of
different molecular structures. This is described as antibody diversity and is necessary to
respond to the huge diversity of molecular structures associated with (often highly mutable)
The simple act of antibody binding may be sufficient to inactivate a pathogen or render a
toxin harmless. For instance, antibody coating of a virus can prevent entry into target cells
and thereby “neutralize” the virus. However, in many instances, a second function of the
antibody molecule is deployed to trigger the elimination of foreign material. In molecular
terms, this involves the binding of certain molecules (effector molecules) to antibody‐coated
foreign material to trigger complex elimination mechanisms, such as the complement system
of proteins, phagocytosis by host immune cells (e.g., neutrophils and macrophages), and
antibody‐dependent cellular cytotoxicity (ADCC) by NK cells. These effector systems are
mainly triggered only by antibody molecules clustered together such as on a foreign cell
surface and not by free unliganded antibody.
The B lymphocyte response to a single antigen may include specific antibody molecules of
all five immunoglobulin classes. Antibodies of different classes may show identical
antigen-binding specificities and thus presumably may possess identical variable (VH + VL)
regions; however, the CH regions mediate different secondary effector functions

1) Complement activation
✓ The classical pathway of complement activation is initiated by the binding of the Cl1
subcomponent to the IgM or IgG component of an antigen-antibody complex.
✓ IgM and IgG can activate alternative pathway under certain circumstances but it is
unclear whether other immunoglobulin classes do so in vivo.
2) Binding to cells
Some immunoglobulins are bound to cell surfaces. Phagocytic cells (monocytes,
macrophages and polymorphs) have receptors which recognize sites in the constant regions
of IgG molecules. Foreign particles coated with IgG antibodies are bound by these receptors,
so triggering rapid phagocytosis (TB infection).
3) Placental transfer
The placental transfer of immunoglobulins provides the newborn infant with an adequate
repertoire of antibody specificities. In humans, only IgG antibodies cross the placenta: this is a
property of the Fc region which interacts with receptors on placental syncytiotrophoblast. The
Fab fragment, although one-third the size of the whole molecule, is not transferred.
The structure of the immunoglobulin classes:

▪ The immunoglobulin classes fulfill different roles in immune defense and this can be
correlated with differences in their structures as organized around the four‐chain Ig
domain arrangement
▪ IgG: is monomeric and the major antibody in serum and non-mucosal tissues, where it
inactivates pathogens directly and through interaction with effector triggering molecules,
such as complement and Fc receptors. In IgG, the Fab arms are linked to the Fc by an
extended region of polypeptide chain known as the hinge. This region tends to be
exposed and sensitive to attack by proteases that cleave the molecule in to its distinct
functional units arranged around the four‐chain structure.
✓ The light chains exist in two forms, known as kappa (k) and lambda (λ). In humans, k
chains are somewhat more prevalent than λ; in mice, λ chains are rare.
✓ The heavy chains can also be grouped into different forms or subclasses, the number
depending upon the species under consideration

▪ IgM is pentameric, is found in serum, and is highly efficient at complement triggering. A

monomeric form of IgM with a membrane‐tethering sequence is the major antibody
receptor used by B‐lymphocytes to recognize antigen. IgM differs from IgG in having an
extra pair of constant domains instead of the hinge region.
▪ IgA exists in three soluble forms. Monomeric and small amounts of dimeric IgA (formed
from two monomers linked by an extra polypeptide called J chain) are found in the serum
where they can help link pathogens to effector cells via Fc receptors specific for IgA.
Secretory IgA is formed of dimeric IgA and an extra protein known as secretory
component (SC) and is crucial in protecting the mucosal surfaces of the body against
attack by microorganisms. IgA exists as two subclasses in humans. IgA2 has a much
shorter hinge than IgA1 and is more resistant to attack by bacterially secreted proteases.
▪ IgE is a monomeric antibody typically found at very low concentrations in serum. In fact,
most IgE is probably bound to IgE Fc receptors on mast cells. Antigen binding to IgE
cross‐links IgE Fc receptors and triggers an acute inflammatory reaction that can assist in
immune defense. This can also lead to unwanted allergic symptoms for certain antigens
(allergens). IgE, like IgM, has an extra pair of constant domains instead of the hinge
▪ IgD is an antibody primarily found on the surface of B‐cells as an antigen receptor
together with IgM, where it likely serves in the control of lymphocyte activation and
suppression. There is also some evidence that free IgD may help protect against microbes
in the human upper respiratory tract. IgD is monomeric and has a long hinge region.

The human immunoglobulin

Class Human Principal Polypeptides Primary Complement

(heavy subclasses molecular location activation
chain forms (pathway)
IgG (γ) IgG1 Monomer γ2, L2 Serum (∼12 IgG3 >
IgG2 mg/mL), IgG1 > >
IgG3 tissues IgG2 > >
IgG4 IgG4
IgA (α) IgA1 Monomer α2, L2 Serum (∼3 Yes
IgA2 mg/mL): (mannose‐
90% binding
Diner (α2, L2)2, J monomer, lectin)
(α2, L2)2, J, 10% dimer
secretory SC
IgM (μ) pentamer (μ2, L2)5, J Serum Yes
(∼1.5 (classical)
IgE ( ε) Monomer ε2, L2 Serum (0.05 No
IgD (δ) Monomer δ2, L2 Serum (30 No

• Classes of immunoglobulins and sub-types

All immunoglobulins have a similar basic subunit structure as seen in our module 1. There are
five classes of antibodies or immunoglobulins, termed immunoglobulin G (IgG), IgM, IgA, IgD,
and IgE. All these classes have the basic four‐chain antibody structure but they differ in their
heavy chains, which are termed γ, μ, α, δ, and ε, respectively and define the corresponding
immunoglobulin classes IgG, IgM. IgA, IgD, and IgE
• IgG:
✓ Some classes can be divided further into subclasses; for example, IgG is divisible into
IgG1, IgG2, IgG3 and IgG4 subclasses.
✓ The light chain is divided into two major types, namely kappa and lambda, associated
with the heavy chains.
✓ In humans there are four subclasses of IgG having heavy chains labeled γ1, γ2, γ3, and
γ4, which give rise to the IgG1, IgG2, IgG3, and IgG4 subclasses. Also in mice, there are
four subclasses denoted IgG1, IgG2a, IgG2b, and IgG3.
✓ The subclasses, particularly in humans have very similar primary sequences, the greatest
differences being observed in the hinge region.
✓ The existence of subclasses is an important feature as they show marked differences in
their ability to trigger effector functions.
✓ In a single molecule, the two heavy chains are generally identical, as are the two light
chains. However, the human IgG4, can exchange heavy–light pairs between IgG4
molecules to produce hybrids.

• IgG, IgD and IgE are each made up of one subunit (monomer).
• IgG and IgE are generally monomeric, whereas IgM occurs as a pentamer
✓ Most of the IgA in normal serum is composed of a single subunit (monomeric IgA), but
the rest, and much of the IgA in secretions, consists of two subunits (Dimer).
✓ IgA occurs predominantly as a monomer in serum and as a dimer in seromucous
secretions (e.g.the lumen).
✓ Serum IgM is a pentamer of five subunits and therefore has 10 antigen-binding sites.
✓ Dimers and pentamers are stabilized by a further polypeptide (J chain) synthesized by
plasma cells
✓ The differences are most pronounced in the Fc regions of the antibody classes and this
leads to the triggering of different effector functions on binding to antigen.
✓ For example, IgM recognition of antigen might lead to complement activation, whereas
the recognition of same antigen by IgE might lead to anaphylaxis and mast cell
degranulation (Degranulation is a cellular process that releases antimicrobial cytotoxic or
other molecules from secretory vesicles called granules found inside some cells).

• Properties of immunoglobulin classes:

1) IgG: IgG are found in body fluids and are the smallest, most common antibody of all the
antibodies of humans. They make up about 75% to 80% of the body’s immunoglobulins.
The IgGs are very important in fighting bacteria and viral infections. They are the only
Igs that can cross the placenta barrier to protect the fetus.
2) IgM: are antibodies are the largest antibody, they are found in blood and the lymph fluid.
They are the first antibodies that are secreted in response to an infection. They also
stimulate cellular immune response, that is cause other cells of the immune systems to
destroy foreign substances. IgM are about the 5% to 10% of all the antibodies in the
3) IgE: are found in the lungs, skin and mucous membrane. They are secreted during an
allergic reaction to allergens. They cause the body to react against foreign substances in
some individuals such as pollen, fungus spores, protein like milk, nuts, some medicine
like chloroquine.
4) IgD: are found in small amounts in the tissues of the body that line the belly or chest,
their mode of function is unknown.
The level of each immunoglobulin can be used for the diagnosis of a disease condition
• Secretion of antibodies


1) Draw the structures of the immunoglobulin classes and label them appropriately.

2) Tabulate the molecular weight of the immunoglobulin classes


1) Thompson E.G., Husney A, Gabica M.J. Healthwise staff Medical review, University of
Michigan, 2019.

2) Mansel Haeney, 'Introduction to clinical immunology’, London Butterworths 1985

3) Roitt's Essential Immunology. Thirteenth Edition. Peter J. Delves, Seamus J. Martin,

Dennis R. Burton, Ivan M. Roitt. 13th edition. | Chichester, West Sussex ; Hoboken, [NJ]
: John Wiley & Sons, Inc., 2017.