Immunoglobulin Structure and Function Now Made Elaborate

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The study of immunoglobulin structure and function is important for you to appreciate the role of immunoglobulin in the immune system. Immunoglobulins are proteins that are also called antibodies when they appear in the blood in response to an infection or any other foreign antigen.

The Basic Immunoglobulin Structure

The human immunoglobulin structure is made up of glycoproteins. Each immunoglobulin consists of two heavy chains (H chains) and two light chains (L chains) which are polypeptide chains. The H chain is approximately 77 kilodalton in size. On the other hand, the L chain is approximately 26 Kilodalton in size.

The two H chains are linked together by disulfide bonds just like the L chains. Further, the two sets of H chains and the two sets of L chains are covalently linked together by disulfide bonds. Therefore, this tells you that disulfide bonds play a critical role in the structure of immunoglobulin.

Both the H and the L chains have variable regions and constant regions. For the H chains, your immunoglobulins have one variable region (VH) and three constant regions (CH1, CH2 & CH3). The immunoglobulin classes with three constant regions include IgG and IgA classes.

There are, however some classes of immunoglobulins with four constant regions instead of three. These include IgM and IgE classes which have CH1, CH2, CH3, and CH4) each. The H chains have a hinge region between CH1 and CH2 which is a flexible region whose molecular analysis has revealed proline (amino acid) as the building blocks.

The presence of proline in this region has been proven to be what makes immunoglobulin breakable through digesting using protease enzymes. Such digestion of the immunoglobulin structure yields an antigen-binding fragment (Fab) and a crystallizable fragment (Fc). The L chains also contain the variable domain (VL) and the constant light domain (CL).

Immunoglobulins Nomenclature

The immunoglobulin nomenclature is about the naming of different immunoglobulins. In this regard, immunoglobulins are named as follows:

Classes

The naming of classes of immunoglobulins is based on small differences in the amino acid subunits within the heavy chain domains. These differences give rise to five classes of immunoglobulins as listed below in the order of abundance in the human blood:

1. Gamma heavy chains – IgG
2. Alpha heavy chains – IgA
3. Mu heavy chains – IgM
4. Delta heavy chains – IgD
5. Epsilon heavy chains – IgE

The immunoglobulin classes are further classified into subclasses based on small molecular differences within the gamma and alpha heavy chains. The subclasses of IgG and those of IgA which are the only ones that do exist are listed here as follows:

Subclasses of IgG

1. Gamma 1 heavy chains – IgG1  
2. Gamma 2 heavy chains – IgG2  
3. Gamma 3 heavy chains – IgG3
4. Gamma 4 heavy chains – IgG4

Subclasses of IgA

1. Alpha 1 heavy chains – IgA1   
2. Alpha 2 heavy chains – IgA2

Further to the classes and subclasses of immunoglobulins, we have discussed above, immunoglobulins are further classified based on the molecular differences within the light chain constant domains. This classification gives rise to immunoglobulin types and subtypes as follows:

Immunoglobulin Types

1. Kappa light chains
2. Lambda light chains

Subtypes of Immunoglobulins

The immunoglobulin types can further be classified based on small amino acid sequence differences within the lambda light chains listed above. These subtypes are listed here as follows:

 Lambda subtypes

1. Lambda 1
2. Lambda 2
3. Lambda 3
4. Lambda 4

Immunoglobulin Classes and Subclasses – Structure and Properties

Your immune system has got five classes of immunoglobulins. These include IgA, IgD, IgE, IgG, and IgM. The listing here is just in alphabetical order and not any other way – it’s easier to remember them all this way. However, our discussion as far as the order of the immunoglobulin classes is concerned shall be according to their abundance in human blood.

Immunoglobulin G (IgG)

Structure

The structure of IgG is organized in subclasses as earlier explained in the previous sections of the article.  All IgG exist as monomers in the human blood. The IgG subclasses have different numbers of disulfide bonds which make the lengths of their hinge regions different.

Properties

The IgG is considered the most versatile in the sense that it can perform all functions of immunoglobulins.

Some properties of IgG are highlighted here:

1. Most abundant in serum accounting for 75% of all immunoglobulins
2. Complement fixation – IgG is able to activate the complement system which is an important immune response during infections
3. Most abundant immunoglobulin in the extravascular spaces. This makes IgG the most available immunoglobulin to protect you from infections in your body.
4. IgG can cross the placenta – This immunoglobulin is the only class that can cross the placenta. What makes it possible for this ability of the IgG is the trophoblastic receptors specific for it at the placenta which aids its binding.
5. IgG can bind to cells – Different immune cells have receptors for IgG allowing them to specifically bind to it. Examples of cells with such receptors include macrophages, all polymorphonuclear cells (PMNs), monocytes, and some lymphocytes. The binding of IgG to these cells aid in phagocytosis where IgG acts as an opsonin.   

Immunoglobulin A (IgA)

Structure

This immunoglobulin class appears are a monomer in the serum. However, in secretions particularly in the mucosa regions of different organs, IgA appears as a dimer as illustrated in the diagram provided in the current section.

IgA is also a special immunoglobulin because it has two additional proteins. One is the J chain that appears in the hinge region of the IgA dimer. The other one is the secretory piece also called the T piece which is added to the IgA dimers as they pass through the epithelial surfaces of our bodies. The T piece is important in protecting the IgA dimers from digestion as they pass through the secretions.

 Properties

1. IgA is the second most abundant serum immunoglobulin – This underscores its importance in the immune system
2. The main immunoglobulin in body secretions – IgA is the most abundant immunoglobulin in the body secretions and in the mucosa protecting you against microorganisms that infect those specific areas
3. Does not fix complement – This means that IgA cannot initiate the activation of the complement system through the classical pathway as IgG and IgM do.
4. Binding of Cells – IgA can bind to some cells like PMNs and lymphocytes that have Fc receptors. This binding helps in making phagocytosis easier and perhaps faster.

Immunoglobulin M (IgM)

Structure

This immunoglobulin normally appears in pentameric form (5-in-1 structure) as illustrated in the diagram provided in this section. In its pentameric form, IgM is considered to have a valency of 10 because all its heavy chain domains are identical. In addition, all its light chain domains are also identical. However, IgM can also appear as a monomer in your blood.

An important structural feature of IgM is that it has two additional domains. One is an additional constant heavy chain CH4 and the other one is the J chain at the hinge region of IgM. These additional features of IgM are important in determining its biological roles and function in our bodies.

Properties

1. IgM is the third most abundant of all immunoglobulins in human serum
2. Complement fixation – Its pentameric form (Valency of 10) enhances its ability to initiate complement system activation.
3. It is the first immunoglobulin to be made by naïve B cells in addition to being the first one to be produced by the immune system of the fetus.
4. Good agglutinin – Owing to its pentameric structure, IgM becomes the most potent agglutin. This feature is important in combating antigens during microbial infections.
5. Serves as the surface immunoglobulin – The B cells have the B cell receptors (BCRs) as their first point of contact with antigens. IgM happens to be one of the immunoglobulins that serve as BCR.

Immunoglobulin D (IgD)

Structure

This immunoglobulin exists as a monomer in the human blood. It has an additional domain called the tailpiece. The tailpiece is what contains the anchor residues that make it possible to have IgD serve as a surface immunoglobulin on the B Cells.

Properties

1. IgD is found in low concentrations in serum – As already mentioned IgD is also anchored on the surface of B cells. This explains why IgD is found in low amounts as free immunoglobulin in human blood.
2. Serves as BCR – IgD serves as the receptor for B cells, BCR. The B cells recognize foreign antigens when the antigens specifically bind to BCR.
3. No complement fixation – IgD does not fix the complement. That means the IgD cannot initiate the activation of the complement system.  

Immunoglobulin E (IgE)

Structure

This immunoglobulin exists in the human blood as a monomer. In addition, IgE has an additional domain CH4 at one end of the heavy chain domains.

Properties

1. This immunoglobulin is the least abundant – IgE binds very strongly to the Fc receptors on the surface of basophils as well as mast cells. This strong binding is what makes the free IgE in the serum to be in low concentrations. Surprisingly, IgE binds to the Fc receptors even before it can interact with antigens.
2. Mediates allergic reactions – in the sensitization stage of allergic reactions, IgE attaches to the basophils and mast cells. In subsequent exposure to the trigger antigens, the antigens cross-link the bound IgE which prompts degranulation of mast cells and basophils. The granules released include histamines which cause clinical signs and symptoms in allergic patients.
3. No complement fixation – IgE is not able to activate the complement system.
4. Helps in parasitic infections immune response – IgE levels rise in helminthic infections meaning that IgE plays an important role in these types of infections. The eosinophils which have been found to have receptors for the Fc region of IgE therefore easily phagocytose the IgE-coated helminths.

Conclusion

An understanding of the immunoglobulin structure is critical as it can help you to understand not only the function but the biological roles of immunoglobulin classes. To manipulate immunoglobulin to come up with therapeutic monoclonal antibodies, scientists only do so after understanding the basic immunoglobulin structure and function.

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