Immunoglobulins (Antibodies): Classes, Functions and Levels

What are Immunoglobulins?

Immunoglobulins are simply proteins that act as antibodies! These proteins are produced by a type of blood cells known as B cells in response to an immunogen. Their role is to identify and neutralize antigens

Immunoglobulins are among the most abundant proteins in the blood since they comprise about 20% of total plasma proteins.

They derive their name from the fact that when the serum that has got antibodies is subjected to a process of electrophoresis, five main peaks of proteins are identified. These are based on their differential ability to migrate in an electric field.

Antibodies are generally drawn as a ‘Y’ shaped structure and when they are in this conformation the heavy chain can be thought of as being ‘inside’ the light chain.

The five classes or isotypes of immunoglobulins are: IgA,IgE,IgD,IgG and IgM

Structure of Immunoglobulins

An immunoglobulin has:

2 heavy chains
2 light chains
chains that are linked together by disulfide bonds
An amino-terminal variable known as (V) region
A carboxyl-terminal constant known as (C) region

Normal Ranges of immunoglobulins:

IgA = 50-350 mg/dL
IgD = <6 mg/dL
IgE = <25 μg/dL
IgG = 800-1500 mg/dL
IgM = 45-150 mg/dL

In this article, we are specifically looking at the causes of elevated immunoglobulin levels

Immunoglobulin A:

Immunoglobulin A exists in three forms which are:

A monomer, a dimer, and dimer plus a secretory piece.

The dimer form is transported across respiratory and intestinal mucosal barriers into the lumen by the secretory piece which is the receptor for immunoglobulin A Fc portion on the epithelium of the mucosa.

There exist two subclasses of IgAα1 and α2.

Properties of immunoglobulin A

This immunoglobulin is found in high concentration in serum

It exists mainly as a dimer with a half-life of 6 days.

Functions of IgA

IgA Protects mucosal tissues, tears, saliva, and colostrum by blocking bacteria, viruses, and toxins from binding to host cells.

Immunoglobulin A is increased in lymphoproliferative disorders such as;

Berger's nephropathy,
Chronic infections,
Autoimmune disorders,
Liver disease.

Immunoglobulin A is decreased in:

Nephrotic syndrome,
Protein-losing enteropathy,
Congenital deficiency,
Lymphocytic leukemia,
Ataxia-telangiectasia,
Chronic sinopulmonary disease.

Immunoglobulin E:

Properties of immunoglobulin E

Immunoglobulin E has four C domains with a molecular weight of 188000d.

It is unstable at 56 degrees and is called a reagin.

There is a very low serum concentration of immunoglobulin E because its Fc region binds avidly to mast cells and basophils.

Function of immunoglobulin E

This immunoglobulin binds to circulating basophils and tissue-bound mast cells via a receptor on their surface. The binding of an antigen to these IgE sensitized cells trigger the release of vasoactive amines mainly histamines. This results in atopic disease characterized by a local reaction known as hives and a systemic reaction known as anaphylaxis.

This immunoglobulin does not cross placenta nor fix complement via a conventional pathway.

Immunoglobulin E levels are elevated in conditions such as;

Allergic_disorders,
Parasitic_infections,
Immunologic disorders,
IgE myeloma,
Acquired Immunodeficiency syndrome (AIDS),
Pemphigoid.

IgE is decreased in:

Hypogammaglobulinemia,
Neoplasm (breast, bronchial, cervical cancers),
Ataxia-telangiectasia.

Immunoglobulin G:

Of all the immunoglobulins, immunoglobulin G has the highest concentration in serum with a half-life of 18-25 days.

Functions of IgG

Complement fixation that eventually causes cell lysis.
Mediates placental passage of maternal antibody to the fetus in the womb.
It also adheres to cells that possess a receptor for Pc fragment from IgG (Fcy)

It is elevated in the following conditions:

Chronic granulomatous infections,
Infectious diseases,
Inflammation,
Myeloma,
liver disease.

IgG is decreased in:

Congenital or acquired deficiency,
Lymphocytic_leukemia,
Drug use such as phenytoin and methylprednisolone,
Nephrotic syndrome,
Protein-losing enteropathy.

Immunoglobulin M

Immunoglobulin M exists in two structural forms. A monomer form is synthesized by B cells and retained also on the membrane of B cells. It serves as the B cell receptor specific for a single antigenic epitope.

Secreted immunoglobulin M exists as a pentamer. This simply means that it exists as five monomeric IgM molecules that are joined together by a J chain.

The pentamer is secreted following antigen and cytokine activation of plasma cells, with hypervariable regions on the pentamer same as those on the membrane-bound monomeric receptors.

IgM has four constant domains on the H and L chains, therefore, its pentamer form has the highest molecular weight of the immunoglobulins.