Antibody : Types, Structure, Classes and Functions

Antibodies or also known as immunoglobulins are proteins produced by the immune system particularly when the immune system detects substances that can be potentially harmful to the body. Antibodies are distinct because they are huge and resemble the shape of letter Y.

Antibodies are important for the function of the immune system. The production of antibodies is carried out by B lymphocyte, which is a type of white blood cell and B cells, which are plasma cells. The antibodies bind to a particular antigen. ^{(1, 2)}

Let us take a look at the structure of antibodies

Antibodies are made up of four polypeptide chains; two of which are heavy chains while the remaining two are light chains. They are bind together by disulfide bonds.

Image 1: The image above shows the structures of the different types of antibodies.

Picture Source: onlinebiologynotes.com

Image 2: A closer look at the structure and property of antibodies.

Picture Source: microbiologyinfo.com

Polypeptides

• Light Chain Polypeptides – They are about 22,000 Da.
• Heavy chain polypeptides – They are around 50,000 Da and even more.
  

Region

• Variable region – It is the region that changes to different structures based on differences in antigens.
• Constant region – It is a region with a constant structure.  ^{(1, 2, and 3)}

Anatomy of polypeptides

Image 3: Polypeptides play an important role in the creation of protein.

Picture Source: study.com

Light Chain polypeptide

1. Has around 220 amino acids.
2. It has a variable region.
3. About 100 amino acids are found at the N-terminal while the remaining are found at the C-terminal.
4. The C-terminal is known as the constant region.
5. In human anatomy, about 60% of light chain polypeptide is kappa and the remaining is a lambda.

Heavy chain polypeptide

1. Around 110 amino acids are found at the N-terminal and are a variable region.
2. The rest of the heavy chain polypeptide is somewhat constant. ^{(4, 5)}

Image 4: The different antibody regions.

Picture Source: wikimedia.org

Antibody classification based on the constant region of heavy chain polypeptide.

Fab Region

The binding of antigen is done by the amino-terminal region and effector function by C-terminal antibody region. In the molecule of antibody, there are two fab regions which bind the antigen.

Fc Region

It facilitates the interaction of the immune complex with phagocytic cells. It also plays a huge role in some biological functions as per the amino acid sequence of every constant region’s domain. ^{(3, 4, and 5)}

Hinge Region

The hinge region consists of γ, δ and α heavy chain with extended peptide sequence between the domains CH1 and CH2. The hinge region contains proline residue. It is also flexible, which allows the Fab region to take up various angle and bind to the antigen.

What sets antibody apart from the rest? 

Antibody takes up the following characteristics:

• It is an immunoglobulin molecule.
• It is specific to antigen and works by binding itself to a foreign molecule.
• It is produced by activated B-cells.
• It is the first molecule that participates in a particular immune response.
• Its primary function is to get rid of the foreign invader.
• Its molecules have common structures – four peptide chains: two similar light chain polypeptide and two similar heavy chain large polypeptide. ^{(6, 7, and 8)}

Types/Classes of antibodies

Image 5: The structure, subclasses, and functions of immunoglobulin G.

Picture Source: stackpathdns.com

#1 – Immunoglobulin/Antibody G (IgG)

Characteristics

• It is the most abundant immunoglobulin in serum (80% of total serum immunoglobulin).
• It consists of two light chain polypeptide and two heavy chain polypeptide.
• It has four sub-class: IgG1, 2, 3, and 4 based on decreasing serum concentration.
• Of all antibodies, immunoglobulin G has the longest half-life, which is about 23 days.
• It has the ability to cross the placenta, which provides immunity to the fetus for up to six months of life.

Functions

• It is the primary antibody produced in the secondary immune response.
• It crosses the placenta barrier giving up to six months of protection to the baby inside the womb.
• It is an effective complement activator, specifically immunoglobulin G3.
• It helps immobilize bacteria.
• It has the ability to neutralize toxin and viruses. ^{(8, 9, and 10)}

Clinical Implications

An increase in immunoglobulin G can be indicative of the following:

• Infections
• Liver-related diseases
• Chronic granulomatous infections
• Severe malnutrition
• Hyper-immunization
• Dysproteinemia
• Rheumatoid arthritis
• Hypersensitivity granulomas
• Dermatologic disorders

A decrease in immunoglobulin G can be indicative of the following:

• Lymphoid aplasia
• Immunoglobulin A myeloma
• Selective immunoglobulin G deficiency
• Chronic lymphoblastic leukemia
• Bence Jones proteinemia
• Agammmaglobulinemia ⁽¹¹⁾

#2 – Immunoglobulin/Antibody M

Image 6: A closer look at the structure of immunoglobulin M.

Picture Source: labpedia.net

Characteristics

• It makes up about 10% of the total serum immunoglobulin.
• It is secreted by plasma cell and exits in pentameric form.
• It is called millionaire molecule because of its huge size.
• It has 10 antigen binding sites but the steric hindrance prevents it from binding to 10 complete antigens.
• It is the primary immunoglobulin produced during the main immune response.
• It is the largest antibody in the human body.
• It is produced after an antigen enters the body.
• It is present in the blood and lymph fluid. ^{(12 and 13)}

Structure

• Its heavy chains belong to the Mu subclass.
• It has a total of 10 binding sites.
• It has a molecular weight of 900,000.

Functions

• It is the first antibody produced during the primary immune response.
• It is the very first antibody produced by the neonate.
• It has a high antigen binding site because of the presence of pentameric form.
• It is powerful during the agglutination reaction.
• It has a more efficient complement activation when compared with immunoglobulin G.
• It functions as a secretory immunoglobulin because of J-chain.
• It plays an important role in antigenic recognition.
• It is one of the components of the ABO system blood grouping, which is specific to ABO antigens and is expressed on the red blood cell’s surface. ^{(1, 5, 14, and 15)}

Clinical Implications 

An increase in immunoglobulin M can be indicative of the following conditions:

• Malaria
• Waldenstrom’s macroglobulinemia
• Actinomycosis
• Trypanosomiasis
• Infectious mononucleosis
• Carrion’s disease
• Rheumatoid arthritis
• Lupus erythematosus
• Dysgammaglobulinemia ⁽¹⁶⁾

A decreased in immunoglobulin M can be indicative of the following:

• Lymphoid aplasia
• Agammaglobulinemia
• Myeloma involving immunoglobulin A and G
• Lymphoproliferative disorders
• Chronic lymphoblastic leukemia
• dysgammaglobulinemia

#3 – Immunoglobulin/Antibody A

Image 7: The image above is the structure of immunoglobulin A.

Picture Source: stackpathdns.com

Characteristics

• It consists of about 15% of the total serum immunoglobulin.
• It is present in external secretions such as:
  • Saliva
  • Tears
  • Breast milk
  • Bronchial mucus
  • Digestive and genitourinary tracts

• It exists in monomeric form but can be present in other forms too such as dimeric, tetrameric, and trimeric.
• It has the ability to cross the epithelial layer and enter into the secretion of the body. The process is called transcytosis.
• Immunoglobulin A1 is more prevalent than A2. It is abundant in secretions. ⁽¹⁷⁾

Structure

• The heavy chains are from the alpha subclass.
• It has a total of four antigen binding sites.
• Its molecular weight is 385,000 Da.

Functions

• It has the ability to cross the epithelial layer and associates into the body secretion, which provides immunity in various bodily tracts such as the gastrointestinal, genital, and respiratory.
• It has the ability to neutralize viruses.
• It provides the first line of defense against microbes and antigens.
• It limits the effect of inflammation.
• It plays a huge role in the immune response by activating the complement pathway.
• It gives immunity to both the fetus and the newborn child. ^{(18, 19, and 20)}

Clinical Implications

An increase in immunoglobulin A is indicative of the following:

• Liver cirrhosis
• Wiskott-Aldrich syndrome
• Collagen-related disorder
• Autoimmune-related disorder such as lupus and rheumatoid arthritis
• Immunoglobulin A myeloma
• Chronic infection

A decreased in immunoglobulin A is indicative of the following:

• Hereditary ataxia telangiectasia
• Lymphoid aplasia
• Malabsorption syndrome
• Acute lymphoblastic leukemia
• Immunoglobulin G myeloma
• Immunologic deficiency
• Chronic lymphoblastic leukemia ^{(1, 4, and 8)}

#4 – Immunoglobulin/Antibody D

Image 8: The light and heavy chain structure of antibody D.

Picture Source: stackpathdns.com

Characteristics

• It is present but in extremely low concentration. To be exact, it constitutes 0.2% of the total serum immunoglobulin.
• It is one of the major membrane-bound antibodies that is expressed on mature B-cell.
• It has two sub-classes: Immunoglobulin D1 and D2.
• It is involved in the maturation and proliferation of B cell.
• It is co-expressed on the surface of B cells.

Structure

• Its heavy chain consists of subclass Delta containing two antigen binding sites.
• Its molecular weight is 180,000 Da.
• Found on the surface of the B cell and serves as a receptor. ^{(6, 8, and 10)}

Functions

• It acts as the receptor on the B cell surface and plays an important role in the activation and differentiation of B cell.

Clinical Implications 

An increased in immunoglobulin D is indicative of the following health conditions:

• Infection of chronic type
• Immunoglobulin D myeloma

#5 – Immunoglobulin/Antibody E

Image 9: A closer look at the structure of immunoglobulin E.

Picture Source: wikimedia.org

Characteristics

• It makes up about 0.3% of the total serum immunoglobulin.
• It is called reagenic antibody because it is involved in an allergic reaction. In fact, it is responsible for hypersensitivity reaction as manifested by the symptoms like asthma, hay fever, and anaphylactic shock, to name a few.
• Its Fc region binds on the tissue mast cells and blood basophils. The cross-reaction leads to degranulation of mast cell and basophil leading to the release of histamine; a substance responsible for allergy symptoms.
• It is abundant in the lining of the intestinal and respiratory tracts. ^{(3, 6, 11, and 20)}

Structure

• Its heavy chains are of the subclass Epsilon and comes with a total of two antigenic binding sites.
• Its molecular weight is 200,000 Da.

Functions

• It provides protection against pathogens.
• It plays a huge role in type 1 hypersensitivity reaction/allergic reaction.

Clinical Implications

An increase in immunoglobulin E may indicate the following health conditions:

• Hay fever
• Atopic skin disease like eczema
• Asthma
• Myeloma of the immunoglobulin E
• Anaphylactic shock ^{(19 and 20)}

A decreased in immunoglobulin E may indicate the following conditions:

• Congenital agammaglobulinemia
• Hypogammaglobulinemia secondary to the synthesis of immunoglobulins

Point of comparison	Immunoglobulin M	Immunoglobulin G	Immunoglobulin A	Immunoglobulin E	Immunoglobulin D
Number of antigen binding sites	10	2	4	2	2
Ability to cross the placenta	Cannot cross the placental barrier	Can cross the placental barrier	Cannot cross the placental barrier	Cannot cross the placental barrier	Cannot cross the placental barrier
Molecular weight	900,000 Da	150,000 Da	385,000 Da	200,000 Da	180,000 Da

Antibodies or also known as immunoglobulins are a must for the functions of the immune system. Aside from the immune system response, antibodies are now widely used in treatment methods. They are derived from clones of cells that originate from the parent cells. They are developed and used for treating various types of diseases. ^{(3, 6, 9, and 17)}

To sum it up, immunoglobulins or antibodies are:

1. Antibodies are also called immunoglobulins.
2. They are proteins that resemble the shape of letter Y.
3. They are present in the blood and body fluids of vertebrates.
4. They play an important role in the function of the immune system.
5. They have a unique binding mechanism to tag a microbe/infected cell for attack by the immune system.
6. They have the ability to directly neutralize the target. Every antibody is different from one another.
7. Millions of immunoglobulins have different tip structures.
8. Each variant of antibody binds to different antigen.
9. The diversity of antibodies allows the immune system to distinguish a wide variety of antigen.