Antibody – Structure, Types, Functions and Properties

Antibody or immunoglobulin (Ig) is a specific glycoprotein produced by B-lymphocytes and plasma cells. It is produced in response to entry of foreign substance in the body. These foreign substances are called antigens.

Antibody is an important part of humoral immunity. It is used to identify and bind with bacteria, viruses, toxins and other harmful particles. After binding with antigen, it helps in neutralization and removal of antigen from the body.

Antibody reacts with antigen in a specific manner. The antigenic part which is recognized by antibody is called epitope. The binding part of antibody which binds with epitope is called paratope.

The structure of antibody is Y-shaped. It is formed of four polypeptide chains. There are two similar heavy chains and two similar light chains. These chains are joined with each other by disulfide bonds.

The tip portion of Y-shaped antibody is called variable region. This region binds with specific antigen. The stem portion is called constant region. It decides the class of antibody and also helps in reaction with other immune cells and complement proteins.

In human body, antibodies are mainly of five types. These are IgG, IgA, IgM, IgE and IgD.

IgG is the most abundant antibody in blood. It gives long term immunity. IgA is mainly present in mucosal secretion and protects respiratory tract and gastrointestinal tract.

IgM is the first antibody formed during a new infection. It is important in early immune response. IgE is involved in allergic reaction and defense against parasites. IgD is present mainly on surface of B cells and helps in activation of B cells.

Characteristics of Antibody

The following are the characteristics of antibody–

• Antibody is glycoprotein in nature. It is also known as immunoglobulin (Ig).
• It is produced by B-lymphocytes and plasma cells. It is formed during immune reaction against foreign particles.
• The foreign particle which stimulates antibody formation is called antigen. It may be bacteria, virus, toxin etc.
• Antibody molecule is generally Y-shaped. Its molecular weight is about 150 kDa.
• Antibody is formed of four polypeptide chains. These are two same heavy chains and two same light chains.
• The heavy chains are larger chain. Each heavy chain is about 50 kDa.
• The light chains are smaller chain. Each light chain is about 25 kDa.
• The chains are joined by disulfide bonds. Non-covalent bonds also helps in holding the chains.
• The tip part of antibody is variable region. It has the site for binding with antigen.
• The binding site present on antibody is called paratope. It combines with the antigenic part called epitope.
• Complementarity determining regions (CDRs) are present in variable region. These are hypervariable loops and gives specific nature to antibody.
• The stem part of antibody is constant region. This region determines the class of antibody.
• The constant region also takes part in immune reaction. It can bind with immune cell receptors and activates complement system.
• A flexible hinge region is present in most antibody. It allows movement of two arms of antibody.
• Antibody is generally bivalent. It has two same antigen binding sites.
• Antibodies are classified into five classes. These are IgG, IgA, IgM, IgE and IgD.
• The classification is based on difference in heavy chains. Each class performs different role in immune response.

Structure of Immunoglobulins/Antibody

The structure of immunoglobulin or antibody is as follows-

• Antibody molecule is generally Y-shaped in structure. It is made up of two arms and one stem like region.
• It is formed of four polypeptide chains, which include two identical heavy chains (H-chains) and two identical light chains (L-chains).
• The heavy chains are larger in size and forms the main part of the antibody molecule. The light chains are smaller and attached with the heavy chains.
• The chains are connected with each other by disulfide bonds. These bonds help in maintaining the stable Y-shaped structure of antibody.
• The terminal part of the two arms are called variable region (V-region). This region is not same in all antibodies and it is concerned with antigen binding.
• The variable region contains the antigen binding site. This site binds with specific part of antigen called epitope.
• The lower stem part of the antibody is called constant region (C-region). This region is nearly same in antibodies of same class.
• The constant region determines the class of antibody such as IgG, IgA, IgM, IgE and IgD. It also takes part in biological functions of antibody.
• The two upper arms of antibody are called Fab region or fragment antigen binding region. This part is responsible for binding with antigen.
• The stem portion is called Fc region or fragment crystallizable region. It does not bind with antigen, but it binds with immune cell receptors and helps in immune reaction.
• A flexible hinge region is present between the Fab and Fc portion in many antibodies. This region allows movement of two arms, so antigen binding becomes easy.
• The heavy chains and light chains are made up of repeated domains. Each domain contains about 110 amino acids.
• Each domain folds into compact structure called immunoglobulin fold. It is made up of two beta-sheets which are held by intra-chain disulfide bond.

Immunoglobulin Classes/Types of Antibody

The following are the main classes of immunoglobulin–

1. IgG (Immunoglobulin G)– IgG is the most abundant antibody in serum. It forms about 70-75% of total serum immunoglobulin. It is present as monomer. It gives long time immunity against infection. It neutralizes toxins and viruses and also helps in opsonization. It can activate complement system. It is the only immunoglobulin which can pass through placenta, so it gives passive immunity to foetus. The subclasses are IgG1, IgG2, IgG3 and IgG4.
2. IgA (Immunoglobulin A)– IgA is mainly found in mucosal secretion. It is present in saliva, tears, mucus, colostrum and breast milk. It forms about 10-15% of serum immunoglobulin. In serum it is monomer, but in secretion it is dimer and called secretory IgA. It protects the mucosal surface of respiratory tract and intestinal tract. It prevents attachment of pathogen with mucosal surface.
3. IgM (Immunoglobulin M)– IgM is the largest immunoglobulin. It forms about 5-10% of serum immunoglobulin. It is generally present as pentamer. Five antibody units are joined together in it. It is the first antibody formed during primary immune response. It has ten antigen binding sites, so it shows high binding power. It is important in agglutination reaction and strong activation of complement system.
4. IgE (Immunoglobulin E)– IgE is present in very small amount in serum. It is monomer in structure. It is mainly concerned with allergic reaction. It takes part in asthma, hay fever and other allergic condition. It also gives protection against parasitic infection. It remains attached with mast cells and basophils. After contact with allergen, these cells release histamine and other chemicals.
5. IgD (Immunoglobulin D)– IgD is present in very low amount in blood. It is less than 1% of serum immunoglobulin. It is monomer in structure. It is mainly present on the surface of immature B-cells. It acts as receptor for antigen. It helps in selection, maturation and activation of B-cells. Its exact function is not fully clear.

IgG (Immunoglobulin G)

IgG or Immunoglobulin G is the most abundant antibody present in human serum. It is also found in extracellular fluid. It forms about 70-75% of total serum immunoglobulin.

• IgG is monomer in nature. It contains one Y-shaped antibody molecule.
• The molecule is formed of two gamma (γ) heavy chains and two light chains. The chains are joined together and gives the typical antibody structure.
• The molecular weight of IgG is about 150 kDa. It is smaller than IgM, so it can pass easily from blood into tissue spaces.
• IgG is the main antibody of secondary immune response. It is produced in large amount after repeated exposure of same antigen.
• It gives long lasting immunity. So it remains important after infection and also after vaccination.
• IgG combines with viruses and bacterial toxins. It blocks their attachment with host cell and their harmful action becomes neutralized.
• It acts as an important opsonin. It coats the surface of pathogen, so macrophages and neutrophils can recognize and engulf the pathogen easily.
• IgG also activates complement system. This helps in lysis of pathogen and also helps in inflammatory reaction.
• It is the only immunoglobulin which can cross the placenta. It passes from mother to foetus and gives natural passive immunity to the newborn.
• IgG remains for longer time in circulation. The half life of most IgG is about 21 days.
• The long half life is due to neonatal Fc receptor (FcRn). This receptor protects IgG from breakdown and returns it again into blood.
• In human, IgG has four subclasses. These are IgG1, IgG2, IgG3 and IgG4.
  • IgG1 is the major subclass. It forms about 60-70% of total IgG and mainly reacts with protein antigens.
  • IgG2 mainly reacts with bacterial capsular polysaccharide antigens. It is important against encapsulated bacteria.
  • IgG3 is more inflammatory type. It has long flexible hinge region. Its half life is short, about 7 days.
  • IgG4 is formed during chronic antigen exposure. It is more regulatory type and shows Fab-arm exchange.
• The level of IgG is tested to know past infection and immunity after vaccination. It is also used to know immune status of a patient.
• IgG is used in many monoclonal antibody drugs. It is also the main antibody present in intravenous immunoglobulin (IVIG) preparation.

IgA (Immunoglobulin A)

IgA or Immunoglobulin A is an important antibody of mucosal immunity. It is present in serum but the main amount is found in mucosal secretions. It protects the body surface which is continuously exposed to outside environment.

• IgA forms about 10-15% of total serum immunoglobulin and it is second most abundant antibody in blood. But in the whole body, IgA is produced in highest amount than other antibody classes. It is mainly present in saliva, tears, mucus, colostrum, breast milk, respiratory tract, gastrointestinal tract and urogenital tract.
• In serum, IgA is generally present as monomer. It is formed of two alpha (α) heavy chains and two light chains. In mucosal secretion, it is present mostly as dimer and called secretory IgA (sIgA). In this form two IgA molecules are joined by J-chain.
• Secretory IgA has a secretory component attached with it. This component protects IgA from the action of enzymes present in mucosal secretion. Due to this, IgA can remain stable in mucosal surface and perform its protective function.
• The main function of IgA is protection of mucosal surface. It prevents attachment of bacteria, viruses and toxins with epithelial cells. This process is referred to as immune exclusion. In this process antigen is blocked before it enters into the tissue.
• IgA also neutralizes toxins and pathogens in secretion. It helps to control infection at the entry site itself. It also helps in maintaining normal microbial flora, so useful microorganisms remain in balanced condition.
• IgA is important for newborn baby. It is present in high amount in colostrum and breast milk. The IgA received from mother gives passive immunity to infant and mainly protects the intestine and mucosal surface.
• In human, IgA has two subclasses, IgA1 and IgA2. IgA1 is the major form in serum and forms about 85% of serum IgA. It has long flexible hinge region, but it can be cleaved by some bacterial proteases.
• IgA2 is more common in mucosal secretion. It is found in higher amount in lower gastrointestinal tract and female reproductive tract. It has shorter hinge region, so it is more resistant to bacterial proteases and useful in mucosal defence.
• Selective IgA deficiency is the common primary immunodeficiency. In this condition IgA is very low or absent. The patient may suffer from repeated respiratory infection, gastrointestinal infection, allergy and asthma.
• Abnormal IgA is related with IgA nephropathy. In this disease IgA immune complex gets deposited in kidney and causes inflammation. In celiac disease, IgA anti-tissue transglutaminase antibody and IgA antiendomysial antibody are used as diagnostic markers.

IgM (Immunoglobulin M)

IgM or Immunoglobulin M is the largest antibody present in serum. It is the first antibody produced during primary immune response. It is important in early protection before other antibodies are produced in large amount.

• IgM forms about 5-10% of total serum immunoglobulin. Due to its large size, it mainly remains inside blood vessels. It is not able to pass easily into tissues like IgG.
• IgM may also be present in mucosal surface as secretory IgM. In this form it is transported through epithelial cells and helps in protection of mucosal region.
• In serum, IgM is generally present as pentamer. It means five basic Y-shaped antibody units are joined together. These units are connected by disulfide bonds and one J-chain.
• IgM has molecular weight about 900 kDa. So it is much heavier than other immunoglobulins. Each antibody unit contains two mu (μ) heavy chains and two light chains.
• The mu (μ) heavy chain is larger than heavy chain of many other antibodies. It contains four constant domains, while many other heavy chains have three constant domains.
• IgM is also present as monomer on the surface of B-cells. In this condition it acts as B-cell receptor (BCR). It helps the B-cell to recognize specific antigen.
• IgM is the first antibody secreted after new antigen enters into body. So its presence mainly indicates early immune response. Later, other antibody like IgG becomes more important for long term immunity.
• IgM has total ten antigen binding sites because of its pentameric structure. Each binding site may not be very strong in early stage, but all binding sites together gives very high binding power. This is called high avidity.
• IgM is very effective in agglutination reaction. It can bind many antigen particles at the same time and forms large clumps. These clumps are then easily removed by phagocytic cells.
• IgM is a strong activator of classical complement pathway. After binding with antigen, it activates complement proteins and helps in destruction of pathogen.
• IgM is important in diagnosis of recent infection. When specific IgM is found in blood, it usually shows acute, early or recent infection.
• During immune response, IgM level first rises and then gradually decreases. After this, IgG level increases and gives longer protection. So IgM is mainly the antibody of early phase of infection.

IgE (Immunoglobulin E)

IgE or Immunoglobulin E is an antibody mainly related with allergic reaction and parasitic infection. It is present in very small amount in serum, but its action is very important in tissue level. It is mostly attached with mast cells and basophils.

• IgE is the least abundant antibody in blood. It forms only about 0.002-0.05% of total immunoglobulins. So it is present only in trace amount in serum.
• IgE is mainly found in tissues. It remains tightly attached with mast cells and basophils by its Fc region. It may also be present in saliva and nasal secretion.
• IgE is monomer in structure. It is formed of two epsilon (ϵ) heavy chains and two light chains. Its molecular weight is about 200,000 Da.
• The epsilon heavy chain is larger than many other antibody heavy chains. It has four constant domains, CH1, CH2, CH3 and CH4.
• IgE has very short half life in serum. It remains in blood only for about 2 days. But when it is attached with mast cells and basophils, it can remain for longer time.
• The main function of IgE is in type I hypersensitivity reaction. It takes part in allergic conditions like asthma, hay fever, eczema and anaphylaxis.
• IgE also gives protection against parasitic and helminthic infections. It helps in activation of cells which can act against large parasites.
• IgE binds with high affinity Fc receptor present on mast cells and basophils. This receptor is called FcϵRI.
• When allergen enters the body, it binds with IgE molecules present on mast cell surface. The allergen cross-links the IgE molecules and then mast cell becomes activated.
• After activation, mast cells and basophils show degranulation. They release histamine and other inflammatory mediators. Due to this itching, swelling, mucus secretion, bronchoconstriction and other allergic symptoms are produced.
• IgE reaction also helps in recruitment of eosinophils. These cells are important in killing of parasites and also take part in allergic inflammation.
• Increased IgE level is seen in allergic diseases and parasitic infections. It is also found very high in rare immune disease called hyper-IgE syndrome.
• IgE level is used clinically to know allergic condition of patient. Specific IgE test can show sensitivity against particular allergen.
• Severe allergic reactions may be controlled by allergen immunotherapy. It changes the immune response against allergen slowly and reduces IgE mediated reaction.
• Some monoclonal antibody drugs are made against IgE. Example is omalizumab, which binds with free IgE and prevents its attachment with mast cells and basophils.

IgD (Immunoglobulin D)

IgD or Immunoglobulin D is one of the antibody class present in very small amount in serum. It is mainly present on the surface of immature B-cells. It acts mostly as B-cell receptor (BCR) and helps in regulation of B-cell activity.

• IgD is present in very low concentration in blood. It forms about 0.03-0.1% of total serum immunoglobulins. So it is not a major circulating antibody like IgG or IgA.
• Most of the IgD remains attached on the membrane of B-cells. It is found mainly on immature and mature naive B-cells along with IgM. Some amount of IgD may also be present in mucosal areas.
• IgD is monomer in structure. It is formed of two delta (δ) heavy chains and two light chains. The light chain may be kappa (κ) or lambda (λ) type.
• IgD does not have subclasses. This is different from IgG and IgA, where subclasses are present.
• The half life of IgD in serum is short. It remains about 3 days in blood. Due to this its free serum amount is very less.
• The main function of IgD is to act as antigen receptor on B-cells. When antigen binds with membrane bound IgD, it helps in activation of B-cell.
• IgD takes part in B-cell selection, maturation and differentiation. It helps the B-cell to respond against proper antigen.
• It also helps in maintenance of peripheral tolerance and immune homeostasis. So unnecessary activation of B-cells can be controlled.
• The exact function of IgD is not fully clear. But it is known that it has important role in regulation of B-cell response.
• In routine diagnosis, IgD has less clinical importance than other antibodies. It is not commonly measured like IgG, IgM or IgE.
• Increased level of serum IgD may be seen in hyper-IgD syndrome. This is an autoinflammatory condition where recurrent fever and inflammation may occur.
• Recent studies also show that IgD may act through a receptor called FcδR. This pathway may be useful as therapeutic target in some autoimmune and blood related diseases.

Antigenic Determinants (Epitopes) on Immunoglobulins

Immunoglobulins are protein molecule. So they can also behave as antigen in some condition. The antigenic sites present on immunoglobulin molecule are called antigenic determinants or epitopes.

These determinants are mainly present due to difference in structure of heavy chain, light chain and variable region. The following are the antigenic determinants of immunoglobulins–

• Isotypes– Isotypes are the antigenic determinants present in the constant region of immunoglobulin. These are same in all normal individuals of a species. It forms the main classes of antibody. The type of heavy chain decides the class of immunoglobulin. IgG has γ-chain, IgA has α-chain, IgM has μ-chain, IgD has δ-chain and IgE has ε-chain. The light chain also has two isotypes, kappa (κ) and lambda (λ).
• Allotypes– Allotypes are the small antigenic differences present in immunoglobulin of different individuals of same species. These differences are due to genetic variation. It is present mainly in constant region of heavy chain or light chain. Allotype does not change the main class of antibody, but it gives individual difference in antibody molecule.
• Idiotypes– Idiotypes are the antigenic determinants present in the variable region of antibody. It is mainly present near the antigen binding site or paratope. These determinants are different in different antibody molecules. So it is related with the specificity of antibody. Antibodies having same idiotype can bind with same epitope of antigen.

Isotype, allotype and idiotype are the three antigenic determinants of immunoglobulin. Isotype is related with class difference. Allotype is related with individual genetic difference. Idiotype is related with antigen binding specificity.

Antigen Binding Sites (B-cell Receptors)

The following are the important points of antigen binding sites or B-cell receptors–

• Antigen binding site is the specific region of antibody or B-cell receptor (BCR) which combines with antigen. It recognizes the particular part of antigen called epitope.
• The antigen binding site is also called paratope. It is complementary with the epitope of antigen. So antigen and antibody binding is specific type.
• In antibody molecule, the antigen binding sites are present at the tip of two arms of Y-shaped structure. So one antibody monomer has two antigen binding sites.
• Before secretion, the antibody molecules are present on the surface of B-cells. These membrane bound antibody molecules act as B-cell receptors.
• A newly formed B-cell contains many B-cell receptors on its surface. When proper antigen binds with these receptors, the B-cell becomes activated.
• After activation, B-cell divides and forms many cells. Some cells become plasma cells and produces soluble antibodies in large amount.
• Each antigen binding site is formed by the variable part of heavy chain (VH) and variable part of light chain (VL). These two variable domains come together and forms the binding surface.
• The actual binding part contains complementarity determining regions (CDRs). These are also called hypervariable regions.
• There are six CDR loops in one antigen binding site. Three are from heavy chain and three are from light chain.
• Only few amino acids of these CDR loops directly touches the antigen. Usually about 15-20 amino acids make contact with antigen.
• Antigen binding is not by permanent chemical bond. It occurs by weak non-covalent forces like hydrogen bond, Van der Waals force, electrostatic interaction and hydrophobic interaction.
• These weak bonds are reversible. But when many bonds act together, the binding becomes strong and stable.
• The shape of antigen binding site is different in different antibodies. It may be pocket like, groove like, flat surface or projection like structure.
• This different shape is due to variation in amino acid sequence of CDR loops. Because of this variation, antibody can recognize large number of antigens.
• Sometimes the binding site changes slightly after contact with antigen. This is called induced fit. It helps in better fitting between paratope and epitope.
• A simple antibody monomer is bivalent. It means it has two same antigen binding sites and can bind with two same antigenic determinants.
• Due to bivalency, antibody can cross-link antigens. This helps in formation of larger antigen-antibody complex for removal by immune system.

Biosynthesis of Antibody

The following are the steps of antibody biosynthesis–

Step 1- Development of B-cell in bone marrow
The formation of antibody starts from developing B-cells in bone marrow. In this stage the B-cell undergoes genetic rearrangement. This process is called V(D)J recombination.

Step 2- Gene rearrangement
During V(D)J recombination, the V, D and J gene segments are joined in different combination. This gives a different antigen binding site to each B-cell. So each B-cell becomes specific for one type of antigen.

Step 3- Formation of B-cell receptor
After gene rearrangement, the mature naive B-cell forms surface antibodies. These antibodies are mainly IgM and IgD. They remain attached on the plasma membrane and act as B-cell receptors (BCRs).

Step 4- Movement of naive B-cell
The naive B-cells then move from bone marrow to peripheral lymphoid organs. These organs include lymph node, spleen and other lymphoid tissues. Here the B-cells wait for the entry of suitable antigen.

Step 5- Antigen binding
When the specific antigen comes, it binds with matching B-cell receptor. The binding occurs between epitope of antigen and paratope of B-cell receptor. This is the first signal for activation of B-cell.

Step 6- Activation of B-cell
The B-cell becomes fully activated after antigen binding. In most cases help from helper T-cells is also needed. These T-cells give stimulatory signals to the B-cell.

Step 7- Multiplication of B-cell
The activated B-cell divides rapidly and forms many similar cells. This is called clonal proliferation. All these cells produce antibody against the same antigen.

Step 8- Somatic hypermutation
In this step, small changes occur in the antibody gene of activated B-cells. This is called somatic hypermutation. It helps to improve the binding strength of antibody with antigen.

Step 9- Class switching
Some activated B-cells change the class of antibody. At first mainly IgM is produced. Later it may change to IgG, IgA or IgE according to immune need. This process is called class switching.

Step 10- Differentiation into plasma cell
The activated B-cells then differentiate into plasma cells. Plasma cells are antibody secreting cells. They are specialized for producing large amount of antibody.

Step 11- Secretion of antibody
The plasma cells produce and secrete soluble antibodies into blood and body fluids. A plasma cell can release very large number of antibody molecules, about 2000 molecules per second. These antibodies then bind with antigen and helps in removal of infection.

Mechanism of action of Antibody

The mechanism of action of antibody takes place in the following steps-

Step 1- Antigen recognition
In this step antibody first recognizes the foreign antigen. The antigen may be present on bacteria, virus, toxin or any abnormal cell. The binding part of antibody is called paratope. It combines with specific part of antigen called epitope.

Step 2- Formation of antigen-antibody complex
After recognition, antibody binds with the antigen. This binding is specific type. As a result antigen-antibody complex is formed. This complex then starts different immune reactions in the body.

Step 3- Neutralization
In this process antibody directly binds with pathogen or toxin. The active site of pathogen becomes blocked. So the pathogen cannot attach with host cell and cannot enter into the cell. The toxic effect is also neutralized.

Step 4- Agglutination
A normal antibody has two antigen binding sites. So one antibody can bind with two same antigens at a time. In this way many antigen particles are joined together and form clumps. This clumping process is called agglutination.

Step 5- Opsonization
In this step antibody coats the surface of pathogen. The pathogen becomes marked for destruction. The Fc region of antibody is recognized by phagocytic cells like macrophages and neutrophils. Then these cells engulf and digest the pathogen.

Step 6- Complement activation
The antigen-antibody complex can activate the classical complement pathway. The Fc region of antibody binds with complement protein like C1q. Then a series of complement reactions are started.

Step 7- Formation of membrane attack complex
After complement activation, membrane attack complex (MAC) is formed on the pathogen membrane. It makes pores in the membrane. Due to this the pathogen cell swells and finally lysis occurs.

Step 8- Antibody dependent cellular cytotoxicity (ADCC)
In this process antibody binds with virus infected cell or tumour cell. The exposed Fc region is recognized by Natural Killer (NK) cells. Then NK cells release perforin, granzymes and other lytic substances.

Step 9- Destruction of target cell
The lytic substances enter into the abnormal target cell. They damage the cell and cause cell death. Thus infected cell or tumour cell is removed from the body.

Step 10- Removal of antigen
Finally the antigen is removed by phagocytosis, complement lysis, neutralization or ADCC. In this way antibody protects the body from infection and harmful foreign substances.

The Immunoglobulin Superfamily

Immunoglobulin superfamily is a large group of proteins which have immunoglobulin domain or immunoglobulin like domain in their structure. These proteins may be present in immune cells and also in many non-immune cells. They are mainly involved in recognition, binding, adhesion and cell communication.

• The main character of immunoglobulin superfamily is the presence of Ig domain. This domain is a repeated structural unit present in many proteins. Due to this common structural unit, these proteins are placed in one superfamily.
• The Ig domain usually contains about 110 amino acids. It folds into a compact structure which is called immunoglobulin fold. This fold is the basic structural pattern of this whole superfamily.
• In immunoglobulin fold, two anti-parallel beta sheets are arranged face to face. These beta sheets form a sandwich like structure. The structure is stabilized by internal disulfide bond.
• It is believed that the members of immunoglobulin superfamily developed from one ancestral gene. Repeated gene duplication and modification produced many different proteins having same basic Ig fold.
• Antibodies or immunoglobulins are the main members of this superfamily. These include IgG, IgA, IgM, IgE and IgD. They are Y-shaped proteins and take part in humoral immune response.
• T-cell receptors (TCRs) are also important members of immunoglobulin superfamily. These receptors are present on T-cells and bind with antigen presented by MHC molecules. Their antigen binding part is similar in arrangement with antibody binding region.
• Many cell adhesion molecules are also included in this superfamily. These molecules help in cell to cell recognition and attachment. They are important in nervous system, immune system and different tissues.
• Other immune cell surface proteins and receptors also contain Ig-like domains. These proteins are present on lymphocytes and other cells. They help in immune recognition, signaling and interaction between cells.
• As many proteins of this superfamily have similar structural framework, special numbering systems are used for their comparison. IMGT and Honegger (AHo) numbering systems are used to align and study variable domains of these proteins.
• immunoglobulin superfamily includes many different proteins, but their basic structural plan is same. The presence of Ig fold makes them related, although their functions may be different in immune and non-immune tissues.

Diseases related with Antibody

The following are the diseases related with abnormal antibody level and function-

A. Diseases due to low antibody level

• Hypogammaglobulinemia– It is a condition where immunoglobulin level becomes low in blood. One or more class of antibody may be decreased. Due to this the person suffer from repeated infections.
• Selective IgA deficiency– In this disease IgA is very low or absent. It is one of the common primary immunodeficiency. The patient mainly gets repeated respiratory infection, chest infection and allergic diseases.
• X-linked agammaglobulinemia– It is a genetic immunodeficiency disease. Here B-cells do not mature properly. So antibody production becomes very less and bacterial infections occur again and again.
• Secondary immunodeficiency– It is caused by other external or acquired causes. It may occur in HIV infection, malnutrition, bone marrow failure and after chemotherapy. In this condition antibody formation is reduced.

B. Autoimmune diseases related with antibody

• Systemic lupus erythematosus (SLE)– It is an autoimmune disease. In this disease antibodies are formed against own body tissues. Increased IgG and different autoantibodies are found.
• Rheumatoid arthritis– It is an autoimmune disease of joints. Abnormal antibody like rheumatoid factor is present. It causes pain, swelling and stiffness of joints.
• Immune thrombocytopenia (ITP)– It is a blood autoimmune disease. Antibody is formed against platelets. Platelets are destroyed and bleeding spots or purpura may occur.
• Guillain-Barre syndrome– It is an autoimmune disease of peripheral nerves. Abnormal antibody reaction damages the nerves. IVIG is used in treatment of this disease.
• Chronic inflammatory demyelinating polyneuropathy (CIDP)– It is a chronic nerve disease. Immune reaction damages the myelin sheath of nerve. Intravenous immunoglobulin (IVIG) is used as treatment.
• Celiac disease– It is an autoimmune disease related with gluten. In this disease abnormal IgA response is present. IgA anti-tissue transglutaminase and antiendomysial antibodies are used for diagnosis.
• Kawasaki disease– It is an inflammatory disease of children. Blood vessels are affected in this disease. IVIG is given to reduce the chance of coronary artery aneurysm.

C. Allergic diseases

• Allergic diseases– These are mainly related with increased IgE. It causes type I hypersensitivity reaction. The diseases include asthma, eczema, hay fever, food allergy and anaphylaxis.

D. Diseases due to excess antibody production

• Multiple myeloma– It is a cancer of plasma cells. In this disease one type of monoclonal immunoglobulin is produced in very high amount. Mostly IgG or IgA is increased.
• Hypergammaglobulinemia– It is a condition with excess immunoglobulin in blood. It usually occurs in chronic infection and chronic inflammatory disease.
• Hyper-IgE syndrome– It is a rare immune disorder. IgE level becomes very high in blood. Recurrent infection and allergic manifestations are seen.
• Hyper-IgD syndrome– It is an autoinflammatory disease. Serum IgD level is increased. Recurrent fever and inflammatory symptoms are present.

E. IgA related diseases

• IgA nephropathy– It is a kidney disease. Abnormal IgA immune complex gets deposited in glomeruli of kidney. It causes inflammation and may lead to kidney damage.
• Henoch-Schonlein purpura (HSP)– It is a systemic vasculitis of children. It occurs due to deposition of IgA and complement in small blood vessels. Skin, joint, gastrointestinal tract and kidney are affected.
• Linear IgA bullous dermatosis– It is an autoimmune blistering disease of skin. It occurs due to IgA deposition in skin. Sometimes it is produced by drug like vancomycin.
• IgA pemphigus– It is also an autoimmune blistering skin disease. IgA antibodies act against the skin cell surface. Due to this blisters are formed.

Functions of Antibody

The following are the main functions of antibody–

• Neutralization– In this process antibody combines with virus, bacteria or toxin. The active part of antigen becomes blocked. So the antigen cannot attach with host cell and its harmful effect is neutralized.
• Opsonization– Antibody covers the surface of pathogen. This makes the pathogen more easy for recognition by macrophages and neutrophils. Then these cells engulf the pathogen by phagocytosis.
• Complement activation– The antigen-antibody complex can activate complement system. After activation, complement proteins act on the pathogen surface. This may cause lysis of pathogen and inflammation at the site of infection.
• Agglutination– Antibody has two antigen binding sites. It can bind with more than one antigen at same time. Due to this, many antigen particles are joined together and forms clumps. This is called agglutination.
• Antibody dependent cellular cytotoxicity (ADCC)– In this reaction antibody binds with infected cell or tumour cell. The Fc region of antibody is recognized by Natural Killer (NK) cells. Then the target cell is killed by lytic substances.
• B-cell activation– Some antibodies are present on the surface of B-cells. These antibodies act as B-cell receptors (BCRs). Mainly IgD and IgM are present in this form. After binding with antigen, B-cell becomes activated.
• Defence against parasites– IgE is important against parasitic infections. It is attached with mast cells and basophils. After contact with parasite antigen, inflammatory chemicals are released.
• Allergic reaction– IgE also takes part in allergic reactions. It causes release of histamine from mast cells. This produces allergy like asthma, hay fever and other hypersensitivity reactions.

Clinical applications of Antibody

The following are the clinical applications of antibody–

A. Diagnostic applications

• Disease diagnosis– Antibodies are used in different diagnostic tests. It is used in ELISA, lateral flow test, rapid test and other immunological test for detection of disease.
• Detection of infection– IgM and IgG antibodies are measured to know the stage of infection. IgM usually shows recent or acute infection. IgG shows past infection or immunity.
• Detection of antigen– Specific antibody is used to detect antigen of bacteria, virus, toxin and other pathogen. This is used in many laboratory diagnosis.
• Biomarker detection– Antibodies are used to detect different biomarkers in blood or tissue. It helps in diagnosis of cancer, degenerative disease and other abnormal conditions.
• Cancer cell detection– Monoclonal antibodies are used to identify specific marker present on cancer cells. So it helps in diagnosis and classification of tumour.

B. Therapeutic applications

• Monoclonal antibody therapy– Monoclonal antibodies are used as targeted treatment. It is used in cancer, autoimmune disease, inflammatory disease and some infectious diseases.
• Cancer treatment– Antibodies bind with specific antigen present on tumour cell. Then the tumour cell is destroyed by immune mechanism or by attached drug.
• Autoimmune disease treatment– Some antibodies are used to block inflammatory mediators. It is used in diseases like rheumatoid arthritis, inflammatory bowel disease and other autoimmune conditions.
• Intravenous immunoglobulin (IVIG)– IVIG is prepared from plasma of healthy donors. It is given to patients with antibody deficiency and some autoimmune diseases.
• Use of IVIG in diseases– IVIG is used in primary immunodeficiency, Guillain-Barre syndrome, Kawasaki disease, ITP and some neurological immune disorders.
• Allergy treatment– Some antibody treatment is used to control IgE mediated allergic reaction. It reduces severe allergy, asthma and other hypersensitivity condition.
• Immune stimulation– Some antibodies are made to stimulate immune cells. These antibodies activate T-cells or antigen presenting cells and helps in anti-tumour immunity.

C. Advanced antibody applications

• Antibody drug conjugate (ADC)– In this method antibody is joined with cytotoxic drug. The antibody carries the drug to tumour cell and kills the malignant cell with less damage to normal cell.
• Antibody radionuclide conjugate (ARC)– In this method antibody is joined with radioactive isotope. It carries radiation directly to tumour tissue. It is used in some lymphoma and other cancer treatment.
• Immunotoxin– In this method antibody or antibody fragment is joined with toxin. It enters into target cell and inhibits protein synthesis. Finally cell death occurs.
• Antibody directed enzyme prodrug therapy (ADEPT)– In this method antibody carrying enzyme reaches tumour site. Then a non-toxic prodrug is changed into toxic drug near cancer cells.
• Bispecific antibody– These antibodies can bind two different targets. One side binds with tumour cell and other side binds with immune cell. In this way immune cell is brought near tumour cell for destruction.
• CAR T-cell therapy– In this method T-cells are modified with receptor made from antibody fragment. These modified T-cells recognize tumour antigen and kill the tumour cell.

D. Nanobody applications

• Nanobody– Nanobodies are small single domain antibody fragments. These are used in diagnosis, imaging and targeted treatment because of their small size.
• Blood brain barrier delivery– Nanobodies can be used as carrier to cross blood-brain barrier. It may help in treatment of central nervous system diseases.
• Photothermal therapy– Nanobody can be joined with gold nanoparticle. After reaching tumour cell, laser is applied and heat is produced. This heat destroys cancer cells.
• Viral neutralization– Nanobodies can bind with hidden part of virus. So it can neutralize viruses like SARS-CoV-2 and Ebola virus.

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