An updated review on Immunoglobulin


Rahul Jodh, Mukund Tawar, Prashant Burange, Pradyumna Keche

Department of Pharmacology, P.R. Pote Patil College of Pharmacy, Amravati Ė 444602.

*Corresponding Author E-mail:



Immunoglobulinís are heterodimeric proteins composed of two heavy (H) and two light (L) chains. They can be separated functionally into variable (V) domains that binds antigens and constant (C) domains that specify effectors functions such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events, and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation.† Immunoglobulin is the antibodies and glycoproteinís molecules produced by plasma cells or white blood cells, a signal production occur due the reaction with B cells. In 20th century the science of†† immunoglobulin was considered as an important science, centrifugation, Immuno adsorption such novel techniques was discovered for dissection of human blood components such as antibodies, so the naming of antibodies was necessary, Latin terms was used at that time for the purpose of naming. But the various in vitro studies shows that the pepsin and acidic condition shows a degradative effect on immunoglobulin neutralizing titer. To overcome this the IgY antibodies are encapsulated. For the protection of mucosal membrane of the IgA plays an essential role, the immune response of the secretory IgA is short lived due to this the genetically engineered antibodies are used for passive immunotherapy.


KEYWORDS: Immunoglobulin, Antibodies, Glycoprotein, Novel Techniques, Immunogens.




Immunoglobulinís stands for the glycoproteins which are secreted by the plasma cells. Immunoglobulin constitutes of 20% of plasma proteins. Immunogens reacts with the B cells and receptor that are located on B lymphocytes and a signal production takes place which is liable for the activation of transcription factors to stimulate antibodies which are highly specific for antigens which are responsible for B cell stimulation1-3.



In the 20th century, the Immunology was come to light as an important scientific study. Novel techniques such as centrifugation, immunoadsorption had been discovered and were using for dissection of the human blood proteins which included antibodies and compliment, at that time it was necessary to name those proteins in constituent manner. Some attempts were followed for designating those terms by Greek words for making a science based nomenclature and for separating it from the normal language, as the similar naming system was already present in physics like alpha and beta. In 1964, the World Health Organization (WHO) coined a proper order for proper naming of each isotype. The original names was given to the proteins by the discovers as IgM, IgG etc4-6.


Antigen Recognition and the Fab:

Early studies of Ig structure were facilitated by the use of enzymes to fragment IgG molecules. Papain digests IgG into two Fab fragments, each of which can bind antigen, and a single Fc fragment. Pepsin splits IgG into an Fc fragment and a single dimeric F (ab) 2 that can cross-link as well as bind antigens. The Fab contains one complete L chain in its entirety and the V and CH1 portion of one H chain. The Fab can be further divided into a variable fragment (Fv) composed of the VH and VL domains, and a constant fragment (Fb) composed of the CL and CH1 domains. Single Fv fragments can be genetically engineered to recapitulate the monovalent antigen binding characteristics of the original, parent antibody4. Intriguingly, a subset of antibodies in a minority of species lack light chains entirely and use only the heavy chain for antigen binding. While these unusual variants are not found in human, there are a number of ongoing attempts to humanize these types of antibodies for therapeutic and diagnostic purposes7-9.


Paratopes, Epitopes, Idiotypes and Isotypes: Immunoglobulin-antigen interactions typically take place between the paratope, the site on the Ig at which the antigen binds, and the epitope, which is the site on the antigen that is bound. In vivo, Immunoglobulins tend to be produced against intact antigens in soluble form, and thus preferentially identify surface epitopes that can represent conformational structures that are noncontiguous in the antigenís primary sequence. This ability to identify component parts of the antigen independently of the rest makes it possible for the B cell to discriminate between two closely related antigens, each of which can be viewed as a collection of epitopes. It also permits the same antibody to bind divergent antigens that share equivalent or similar epitopes, a phenomenon referred to as cross-reactivity10-14.


Immunization of heterologous species with monoclonal antibodies (or a restricted set of immunoglobulinís) allowed the identification of both common and individual immunoglobulin antigenic determinants. Individual determinant(s), termed idiotype(s), are contained within V domains. Common determinants, termed isotypes, are specific for the constant portion of the antibody and allow grouping of immunoglobulinís into recognized classes, with each class defining an individual type of C domain. Determinants common to subsets of individuals within a species yet differing between other members of that species, are termed all types and define inherited polymorphisms that result from gene alleles15-18.


Types of Immunoglobulin19-25:


IgA stands for Immunoglobulin A and it belongs to chief class, plays a vital role in immune protection. Itís† concentration is about 2-4mg/ml† in plasma and it gets metabolized 6 to 7 times faster than IgG , it fulfills various types of functions as , protection of† mucosal surfaces , respiratory and †gastrointestinal lining. IgA has four identical chains, two identical heavy chains and two identical light chains in FAB i.e. Fragment antigen Binding Region and Fc i.e. Fragment Crystalizable Region. These two chains are folded and turns into granular domains and they are immunoglobulin fold but the Fc region is exception for this as it arranged in pairs. In humans there are two forms IgA are their which includes IgA1 and IgA2. IgG ĖImmunoglobulin G is the major and important type of antibody in blood, molecular weight of about 150kDa and it comprises three classes which are IgG1, IgG2, IgG3 and IgG4. Its structure consists of two identical antigen binding arms referred as Fab arms and one Fc stem and there are the hinges for their binding and it works for recognition of antigen. The Fab arms rotated 158 degree whereas Fab Ė Fc angles rotates up to the range of 66-123 degree and the Fab Ė Fab angle ranges from 115 to 170, because of this nature of the IgG the wider range would be available for antigen. IgD Ė Immunoglobulin D is present in low concentration †less than 1% and has little bit role also they have lack† of† structural† requirements† in† for many functions. In structure there is lack of homology of hinge as compared to other immunoglobulin as it is suggested that it has two heavy and two light polypeptide chain. Itís† function† is† not† clear but it is considered as it is located on† the† surface of† lymphocytes† of† blood .



Immunoglobulin M stands as the first agent that provides a protective response against antigens as it is considered as the first class antibodies that are produced after the activation of B cells it is present in high amount in the human serum. It has pentameric structure with J chains i.e. joining chains and hence it becomes helpful for creating a protective action for preventing passage across placenta. It consists of multimeric structure and due to this it is able to bind with spikes of viruses. It has two heavy chains and two light chains like other antibodies and they are symbolically denoted as, μ and L, μ chains include four domains (Cμ1, Cμ2, Cμ3, and Cμ4). Absence of hinge region dose not creates any complications in flexibility of IgM. Monomeric IgM is called as surface bound receptor on B cells and development of B cell is occurred through it.



Immunoglobulin E is an antibody that is produced by immune system of body and it works in response to perceived threat and it is present in blood in very small amount. In the response to antigenic stimulus it is produced by B Cells and plasma cells. It consist of the interleukin as, IL-4 and IL 13 due to presence of these two cytokines the signaling cascade is begun and is carried out by JAK3 and STAT6. There is a need of the second signal for the class that switched IgE due to the switching of IgE the CD40 on B cells interact with CD40 ligand on the T cell. Once the allergen did produce the IgE, it releases into circulation.



IgY is the major antibody of birds, amphibians, reptiles and was first indicated by Klemperner in 1893 and in 1969 Leslie and Clem coined the term IgY. IgY of Chicken and Avian is most commonly studied. As compared to mammalian IgG the IgY has more affinity for binding with the same antigen. In case of passive immunity that means the transfer of readymade antibodies the IgY plays a vital role in controlling various infections like RTIs i.e. Respiratory tract infection. IgY antibodies are well tolerated by the body as, the egg are consumed by the body in regular diet.


Kappa and Lambda Light Chains:

Immunoglobulin† are the Y shaped heterodiameric† proteins which are produced by B cells and they are composed of two light and two heavy chains, IgA, IgG , IgD, IgE, IgM are five heavy chain isotopes and kappa and lambda are two light chain isotopes. The genes which encoded the two chains are present on different chromosomes, kappa gene segments are encoded on chromosomes 2 and consist of 52V genes and 5J genes as long as the gene that encodes the lambda chain is located on chromosome 22 and consist of 30V and 7J genes. Rearrangement of kappa locus leads to the rearrangement of lambda locus and the ratio of kappa/lambda in human peripheral blood was found to 1.5 and 2. However this ratio is differ according to class of antibody heavy chains. There is a one cancer which is associated light chins is myeloma in which more light chains are produced than the heavy chains. As more the light chain, the more aggressive the disease is. This can be diagnosed by Free Light Assay Test on blood specimen. Light chain consist of V and C region in their structure, V region consist of antigen binding site as Vk and Vλ, they also have some other properties that shows the individual difference among the light chains. Homologies in sequence defines chemically their four subgroups of K(K I,K II,K III and K IV) chains and five subgroups of†† λ chains (λ I, λ II , λ III , λ IV and λ VI) and C regions of light chains covalently link with heavy chains by forming disulphide bonds.


Structures of Immunoglobulinís:


Figure 1: Structure of Various Immunoglobulinís


Table 1: Novel Products Related to Immunoglobulinís26

Sr. No

Brand Name

Type Of Immunoglobulin


Name of Company




To prevent Rh incompatibility





To treat primary humeral immunodeficiency.




IgG and IgA in trace amount (<50μg/ml)

To treat primary immune humeral diseases.





Used to strengthen bodyís natural immune system



Histaglobulin injection

Human Normal Immunoglobulin

Used against allergic disorders and allergic rhinitis.





Allergenic bone marrow transplantation Immunodeficiency.


Basic Immunoglobulin Structure and Function:

Antibodies or immunoglobulinís have two light chains and two heavy chains in a light-heavy-heavy-light structure arrangement. The heavy chains differ among classes. They have one Fc region that mediates biological functions (e.g., the binding capacity to cellular receptors) and a Fab region that contains the antigen-binding sites. The chains are folded into regions called domains. There are 4 or 5 domains in the heavy chain, depending on their class, and two domains in the light chain. The hyper variable regions (HRR) contain the antigen-binding sites. There are three HRR in the V domains of each light and heavy chain. These fold into regions that produce 2 antigen-binding sites at the tip of each monomer. All antibodies exhibit one or more functions (bifunctional) including activation of the complement system, opsonization of microbes to be easily phagocytosed, prevention of attachment of the microbes to mucosal surfaces, and neutralization of toxins and viruses26.


Receptors for Immunoglobulinís:

For immunoglobulinís to fulfill various biological functions, they should interact with receptors that are mainly expressed on mononuclear cells, mast cells, neutrophils, natural killer cells, and eosinophils. Again, binding to these receptors is essential for immunoglobulin functions. It promotes several activities including phagocytosis of bacteria (opsonization); mast cell degranulation (as seen in type I hypersensitivity or allergic response); killing of tumors; and activation of antigen-presenting cells including macrophages and dendritic cells, which present antigens to T lymphocytes for the generation of cellular and humoral immune responses25.


The following are immunoglobulin receptors27:

1.    Fc gamma RI (CD64) binds to monomeric IgG is expressed on phagocytes and is involved in the phagocytosis of immune complexes.

2.    Fc gamma RII (CD32) attaches to B-cells, monocyte/macrophages (phagocytes), and granulocytes. On B cells regulates cell activation in the presence of a high titer of antibodies.

3.    Fc gamma RIII (CD16) has 2 types. Fc gamma RIIIa is expressed on macrophages, NK cells, and some T cells. Fc gamma RIIIb is expressed on granulocytes and has a low affinity for IgG.

4.    Fc epsilon RI is a high-affinity receptor for IgE that is shown on mast cells and basophils. It involves an allergic response.

5.    Fc epsilon RII is expressed on leukocytes and lymphocytes and has homology with mannose-binding lectin.


Genetics of Immunoglobulinís:

The immune system can respond to many antigens by generating a vast diversity in immunoglobulinís produced by plasma cells. V and J gene segments encode immunoglobulin light chains. The above genes, in addition to D gene segments, encode the heavy chains. The mechanisms that contribute to this great diversity of immunoglobulin specificities include somatic mutation (immunoglobulin heavy and light chain genes undergo structural modifications after antigen stimulation) and the presence of multiple V-region genes in the germline (antibody diversity also arises when numerous V genes are recombining with J and D segments). Gene conversion, recombinational inaccuracies, nucleotide addition, and assorted heavy and light chains also contribute to the diversity of immunoglobulin molecules27.


Drugs which Activates Immunoglobulin and which depress and suppress it27:

Immunosuppressive Drugs:

Leflunomide, Mycofenolate, Mofetile, Sirolimus, Tacrolimus, Efalizumab, Basiliximab, Myriocin, Cyclosporin.


Immunodepressive Drugs:

Alemtuzumab, Busulfan, Melphalan, Cyclophosphamide, Methylprednisolone


Future Aspects of Immunoglobulinís28-30:

Future opportunities of Immunoglobulins include the investigation of novel dosage form of antibodies. Orally administered antibodies, the orally administered antibodies must remain immunoreactive until it reaches to site of action. In case of local conditions in the gastrointestinal tract, it is essential for the orally administered antibodies or immunoglobulinís to reach the systemic circulation and therefore they have to reach the distal portion of gastrointestinal track without experiencing any proteolysis and denaturation, which would comprises in their immunological responses. The in vitro studies were also going on, on the effect of gastrointestinal protease and the acidity on immunoglobulin structure and activity in order to know their results when they are administered orally, from these studies it appears that the pepsin and the acidic condition has great degradative effect on immunoglobulinís neutralizing titer.


For reducing the degradative effect on immunoglobulinís neutralizing titer, the research has been focused towards developing the oral dosage form of Immunoglobulins. Shimizu et al in his one approach. For stabilizing against the hydrolysis by pepsin and acidic condition encapsulate the IgY antibodies of egg lecithin/cholesterol liposomes. The stability of IgY antibody was improved and this shows that the liposomal encapsulation may prevent the degradation of immunoglobulinís in stomach. Genetically engineered antibodies, Immunoglobulin A i.e. IgA plays an essential role in protecting the mucosal membrane from the microbial infection. As the Immune response of secretory IgA is usually short lived. Due to this the genetically engineered antibodies are used for passive immunotherapy. By using the technique of the antibody phage display library, it is easy to construct the antibodies which are able to neutralize the toxins which affect the gastrointestinal track. To make these anti bodies suitable for producing passive immune response it is possible to generate the IgA and IgM isotypes monoclonal antibodies.



Immunoglobulin becomes an effective tool against the various infections like the infections of the gastrointestinal tract, protection of mucosal membrane. Marketed products of immunoglobulin are well positioned in the pharmaceutical areas. The dosage form of immunoglobulin are successfully prepared for reducing the degradative effect of on immunoglobulin neutralizing titer and the genetically engineered antibodies are also applicable for passive immunotherapy for various disease conditions like infection of gastrointestinal tract.



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Received on 28.12.2021††††††† Modified on 06.04.2022

Accepted on 13.06.2022†† ©AandV Publications All Right Reserved

Res.† J. Pharma. Dosage Forms and Tech.2022; 14(3):224-228.

DOI: 10.52711/0975-4377.2022.00036