Immunoglobulin G (IgG)- Structure, Subclasses and Functions

Immunoglobulin G (IgG) is one of the five classes of antibodies (also known as immunoglobulins) that are produced by the immune system to fight against foreign invaders such as bacteria, viruses and toxins. Antibodies are proteins that can recognize and bind to specific antigens (molecules that trigger an immune response) on the surface of pathogens or other substances. By binding to antigens, antibodies can neutralize them, mark them for destruction by other immune cells or activate various immune mechanisms.

IgG is the most abundant and versatile antibody class in humans, accounting for about 75% of the total serum immunoglobulins. IgG antibodies are involved in many aspects of the immune defense, such as preventing infections, enhancing phagocytosis (the process of engulfing and destroying microbes by specialized cells), activating the complement system (a group of proteins that enhance the immune response) and crossing the placenta to protect the fetus from infections.

The structure of IgG antibodies is complex and consists of four polypeptide chains: two identical heavy chains and two identical light chains. Each chain has a variable region and a constant region. The variable regions are responsible for binding to specific antigens, while the constant regions determine the antibody class and function. The four chains are held together by disulfide bonds (covalent bonds between sulfur atoms) to form a Y-shaped molecule. The two arms of the Y are called Fab fragments (fragment antigen-binding) and contain the antigen-binding sites. The stem of the Y is called Fc fragment (fragment crystallizable) and mediates various effector functions.

There are four subclasses of IgG in humans: IgG1, IgG2, IgG3 and IgG4. They differ in their heavy chain constant regions, which affect their ability to bind to different receptors on immune cells and activate different immune pathways. Each subclass has its own characteristics and roles in the immune response.

In this article, we will discuss the structure, subclasses and functions of IgG antibodies in more detail. We will also explore some of the clinical applications and implications of IgG antibodies in diagnosis, treatment and prevention of diseases.

IgG antibodies are the most abundant type of immunoglobulins in the human body. They are produced by plasma cells in response to foreign antigens, such as bacteria, viruses, or toxins. IgG antibodies have a molecular weight of about 150 kDa and a tetrameric quaternary structure. This means that they are composed of four polypeptide chains: two identical heavy chains and two identical light chains. Each chain has a variable region that determines the specificity of the antibody for a particular antigen, and a constant region that determines the class and subclass of the antibody. The constant regions also mediate various biological functions of the antibody, such as complement activation, opsonization, and placental transfer.

IgG antibodies are considered to be monomeric molecules because they do not form multimers with other IgG molecules. However, some IgG subclasses can form dimers or trimers under certain conditions, such as high antigen concentration or low pH. These multimers may have enhanced avidity and effector functions compared to monomeric IgG molecules.

IgG antibodies have a Y-like shape formed by the tetramer. The two arms of the Y are called Fab fragments and contain the antigen binding sites. The stem of the Y is called Fc fragment and contains the constant regions of the heavy chains. The Fc fragment is responsible for interacting with various receptors and proteins that mediate the immune response. The hinge region connects the Fab and Fc fragments and provides flexibility to the antibody molecule.

IgG antibodies are versatile and can perform various roles in the immune system. They can neutralize toxins and viruses, opsonize bacteria for phagocytosis, activate complement cascade, cross the placenta to protect the fetus, and regulate immune responses by binding to Fc receptors on different cells.

The basic unit of an IgG antibody is composed of four polypeptide chains: two identical heavy chains and two identical light chains. Each chain has a variable region (V) and a constant region (C). The variable regions are responsible for binding to specific antigens, while the constant regions determine the subclass and biological functions of the antibody.

The heavy chains have a gamma (γ) constant region, which defines IgG as a class. The light chains have either a kappa (κ) or a lambda (λ) constant region, which are interchangeable and do not affect the antibody specificity. The heavy and light chains are linked by disulfide bonds between their constant regions.

The basic structure of an IgG antibody can be represented as “H2L2”, where H stands for heavy chain and L stands for light chain. Each H2L2 unit forms a monomer, which is the smallest functional unit of an IgG antibody. A monomer has a molecular weight of about 150 kDa and a tetrameric quaternary structure.

The H2L2 structure can also be visualized as a Y-shaped molecule, where the stem of the Y is formed by the constant regions of the heavy chains (CH), and the arms of the Y are formed by the variable regions of both the heavy (VH) and light (VL) chains. The antigen binding sites are located at the tips of the arms, where the VH and VL regions come together to form a complementary surface for a specific antigen.

The basic monomeric “H2L2” structure of IgG is conserved among all subclasses and species, but there are variations in the length and flexibility of the hinge region between the CH1 and CH2 domains, as well as in the number and position of interchain disulfide bonds. These variations affect the stability, flexibility and biological functions of different IgG subclasses.

As mentioned earlier, IgG antibodies are composed of two identical heavy chains and two identical light chains. The heavy chains are the larger polypeptide chains that form the backbone of the antibody molecule. The light chains are the smaller polypeptide chains that are attached to the heavy chains by disulfide bonds. Each heavy chain and light chain has a variable region and a constant region. The variable regions are the parts of the chains that vary in amino acid sequence among different antibodies and are responsible for binding to specific antigens. The constant regions are the parts of the chains that have a relatively conserved amino acid sequence among different antibodies and are responsible for mediating various effector functions.

The heavy chains of IgG belong to the gamma (γ) class, which is one of the five classes of immunoglobulin heavy chains (the others being alpha, mu, delta and epsilon). The gamma class has four subclasses: IgG1, IgG2, IgG3 and IgG4. These subclasses differ in their hinge regions, which are flexible segments that connect the two arms of the Y-shaped antibody molecule. The hinge regions also contain interchain disulfide bonds that link the two heavy chains together. The subclasses also differ in their constant regions, which determine their ability to activate complement, bind to Fc receptors on various cells and cross the placenta.

The light chains of IgG can be either kappa (κ) or lambda (λ) type, which are two types of immunoglobulin light chains. The kappa and lambda types have different constant regions but similar variable regions. Each heavy chain can associate with either a kappa or a lambda light chain, but not both. Therefore, an IgG antibody can be either κκ (two kappa light chains), λλ (two lambda light chains) or κλ (one kappa and one lambda light chain). The ratio of kappa to lambda light chains in human serum is about 2:1. The type of light chain does not affect the antigen specificity or effector functions of IgG antibodies.

The heavy and light chains of IgG work together to form the antigen binding sites and the Fc region of the antibody molecule. The antigen binding sites are located at the tips of the two arms of the Y-shaped molecule and are formed by the variable regions of both heavy and light chains. Each antigen binding site can recognize a specific epitope on an antigen. The Fc region is located at the base of the Y-shaped molecule and is formed by the constant regions of both heavy chains. The Fc region can interact with various molecules and cells that mediate immune responses, such as complement proteins, Fc receptors, phagocytes and placental cells.

The heavy and light chains of IgG are essential for the structure and function of this important class of antibodies. They determine the antigen specificity, subclass diversity and effector mechanisms of IgG antibodies in humoral immunity.

The tetramer formed by the two heavy and two light chains of IgG has a characteristic Y-like shape. The stem of the Y is called the Fc region, which stands for fragment crystallizable. The Fc region is composed of two identical parts of the heavy chains and contains a conserved N-glycosylation site. The Fc region is responsible for binding to various receptors on immune cells and activating different effector functions, such as opsonization, complement fixation, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).

The arms of the Y are called the Fab regions, which stand for fragment antigen-binding. The Fab regions are composed of one part of each heavy and light chain and contain the variable regions that determine the antigen specificity of IgG. The Fab regions are responsible for binding to antigens with high affinity and specificity. Each Fab region has an antigen binding site at its tip, which is formed by the complementary-determining regions (CDRs) of the variable regions. The CDRs are hypervariable sequences that can recognize a wide range of antigens with different shapes and sizes.

The hinge region connects the Fc and Fab regions and provides flexibility to the IgG molecule. The hinge region allows the Fab regions to move independently and adjust their orientation to bind to different antigens. The hinge region also determines the subclass of IgG, as it varies in size and position of interchain disulfide bonds among the four subclasses. The hinge region is also susceptible to proteolytic cleavage by enzymes such as papain and pepsin, which can generate separate Fc and Fab fragments.

The Y-like shape of IgG enables it to perform multiple functions in the immune system. By having two antigen binding sites, IgG can cross-link antigens and form immune complexes that can be cleared by phagocytes or complement. By having an Fc region that can bind to various receptors on immune cells, IgG can modulate the activity and function of these cells and enhance their ability to eliminate pathogens. By having a hinge region that provides flexibility and diversity, IgG can adapt to different antigens and subclasses and optimize its effector functions.

The antigen binding sites on IgG are located at the ends of the two arms of the Y-shaped molecule. Each site consists of a variable region of a heavy chain (VH) and a variable region of a light chain (VL), which together form a complementary surface for a specific antigen. The variable regions are composed of three hypervariable loops, also called complementarity-determining regions (CDRs), that are responsible for the fine specificity and affinity of the antibody-antigen interaction. The CDRs are flanked by four framework regions (FRs) that provide structural stability to the variable regions.

The antigen binding sites on IgG can recognize a wide range of antigens, such as proteins, polysaccharides, lipids, nucleic acids and small molecules. The antigens can be linear or conformational, meaning that they can be composed of a single or multiple epitopes that are either continuous or discontinuous along the antigen molecule. The antigens can also be soluble or membrane-bound, depending on their location in the body.

The antigen binding sites on IgG are highly specific and selective for their corresponding antigens. This means that they can distinguish between different antigens that share similar structures or sequences, and bind only to those that match their shape and charge. The specificity and selectivity of the antigen binding sites on IgG are determined by the genetic diversity and somatic recombination of the immunoglobulin genes that encode the variable regions. The antigen binding sites on IgG can also undergo affinity maturation and class switching during the immune response, which enhance their ability to bind to their antigens with higher strength and efficiency.

The antigen binding sites on IgG are essential for the function and regulation of the antibody. By binding to their antigens, they can neutralize or block their activity, opsonize them for phagocytosis or complement activation, or mediate antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). The antigen binding sites on IgG can also modulate the expression and signaling of the Fc receptors that recognize the constant region of the antibody, which in turn affect the effector functions and feedback mechanisms of the immune system.

As mentioned earlier, IgG antibodies are composed of four peptide chains: two identical heavy chains and two identical light chains. The heavy chains are of the gamma (γ) type, which defines the IgG class. The light chains can be either kappa (κ) or lambda (λ) type, but each IgG molecule has only one type of light chain.

The heavy and light chains are linked by disulfide bonds, forming a tetrameric quaternary structure with a Y-like shape. Each chain has a variable (V) region and a constant (C) region. The V regions of the heavy and light chains form the antigen-binding sites at the tips of the Y arms, while the C regions form the base of the Y stem.

The heavy chain has four C regions: CH1, CH2, CH3, and CH4. The CH1 region is adjacent to the V region and interacts with the C region of the light chain (CL). The CH2 and CH3 regions form the Fc fragment that can bind to Fc receptors on immune cells or activate the complement system. The CH4 region is only present in IgG3 subclass and contributes to its longer hinge region.

The light chain has two regions: CL and VL. The VL region is adjacent to the VH region and forms part of the antigen-binding site. The CL region interacts with the CH1 region of the heavy chain.

The heavy and light chains of IgG have different roles in antibody structure and function. The heavy chains determine the class and subclass of IgG, while the light chains contribute to antigen specificity. The heavy chains also mediate effector functions such as opsonization, complement activation, and antibody-dependent cellular cytotoxicity (ADCC), while the light chains have no known effector functions.

IgG antibodies are not all the same. They can be divided into four subclasses (IgG1, IgG2, IgG3, and IgG4) based on their structural and functional differences. These subclasses have different distributions in the body, different affinities for antigens, and different abilities to activate the complement system and bind to various receptors on immune cells. The subclasses also vary in their serum concentrations, half-lives, and placental transfer. Understanding the characteristics and roles of each IgG subclass is important for diagnosing and treating various immune disorders and infections.

The four IgG subclasses are distinguished by the type of heavy chain they have. The heavy chain determines the shape and size of the hinge region, which connects the two arms of the Y-shaped antibody molecule. The hinge region also contains interchain disulfide bonds that stabilize the antibody structure. The number and position of these bonds vary among the subclasses, affecting their flexibility and stability. The heavy chain also influences the constant region of the antibody, which is responsible for binding to complement proteins and cellular receptors.

The following table summarizes some of the main features of each IgG subclass:

Each IgG subclass also has a different role in the immune response against various types of antigens. In general, IgG1 and IgG3 are more effective against protein antigens, while IgG2 is more effective against polysaccharide antigens. IgG4 is less involved in antigen recognition and more involved in immune regulation. In the next sections, we will discuss each subclass in more detail.

IgG1 is the most abundant and versatile subclass of IgG, comprising 60 to 65% of the total IgG in serum. It is predominantly responsible for the thymus-mediated immune response against proteins and polypeptides, such as viral and bacterial antigens. It can bind to various receptors on immune cells, such as FcγRI (CD64), FcγRIIA (CD32a), FcγRIIB (CD32b), FcγRIIIA (CD16a), and FcγRIIIB (CD16b), and mediate different effector functions, such as opsonization, phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and activation of the complement cascade. IgG1 can also cross the placenta and provide passive immunity to the fetus.

IgG1 has a relatively long hinge region that allows it to form flexible and stable interactions with antigens. It also has a highly conserved N-linked glycosylation site at Asn297 in the Fc region, which influences its binding affinity and biological activity. The glycosylation pattern of IgG1 can vary depending on the antigen type, the immune status of the individual, and the presence of inflammatory or autoimmune conditions. For example, IgG1 with low levels of fucose or sialic acid in its glycans can have enhanced binding to FcγRIIIA and increased ADCC activity, which may be beneficial for anti-tumor or anti-viral responses. On the other hand, IgG1 with high levels of sialic acid can have reduced binding to FcγRIIA and decreased pro-inflammatory effects, which may be protective against autoimmune diseases.

A deficiency in IgG1 isotype is typically a sign of a hypogammaglobulinemia, a condition characterized by low levels of immunoglobulins in the blood. This can result from genetic defects in B cell development or function, or from secondary causes such as infections, malignancies, or immunosuppressive therapies. Patients with IgG1 deficiency are susceptible to recurrent infections by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, as well as by viruses, such as herpes simplex virus and cytomegalovirus. They may also develop autoimmune disorders, such as rheumatoid arthritis or systemic lupus erythematosus. Treatment options for IgG1 deficiency include immunoglobulin replacement therapy, prophylactic antibiotics, and vaccination.

IgG2 is the second most abundant subclass of IgG in human serum, accounting for about 20 to 25% of the total IgG. It is mainly produced in response to carbohydrate or polysaccharide antigens, such as those found on the surface of bacteria and parasites. IgG2 antibodies are particularly effective at binding to these antigens and preventing their attachment to host cells.

Unlike IgG1 and IgG3, IgG2 antibodies have a shorter hinge region and fewer interchain disulfide bonds, which makes them more flexible and less prone to aggregation. However, this also reduces their ability to activate the complement system, a group of proteins that enhances the immune response by forming pores in the membrane of pathogens and attracting phagocytes. Therefore, IgG2 antibodies rely more on opsonization, the process of coating antigens with antibodies to facilitate their recognition and ingestion by phagocytes.

IgG2 antibodies are also important for conferring passive immunity to newborns through the placenta. They can protect the infant from infections caused by encapsulated bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae type b, which are common causes of meningitis and otitis media. IgG2 antibodies can also neutralize toxins produced by some bacteria, such as tetanus and diphtheria.

A deficiency in IgG2 subclass is the most common type of IgG subclass deficiency and is associated with recurrent respiratory tract infections, especially in children. It can also increase the risk of developing autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. IgG2 deficiency can be caused by genetic factors or acquired conditions, such as immunosuppressive therapy or chronic infections.

IgG2 antibodies are useful for diagnostic purposes, as they can indicate exposure to specific antigens or pathogens. For example, IgG2 antibodies against pneumococcal polysaccharides can be measured to assess the immune status of individuals who have received pneumococcal vaccines or have had pneumococcal infections. Similarly, IgG2 antibodies against tetanus toxoid can be used to evaluate the immune response to tetanus vaccination or infection.

IgG3 comprises around 5 to 10% of total IgG and plays a major role in the immune responses against protein or polypeptide antigens. IgG3 has the longest hinge region among the IgG subclasses, which gives it more flexibility and allows it to bind to multiple epitopes on the same antigen. IgG3 also has more disulfide bonds and glycosylation sites than other IgG subclasses, which affect its stability and effector functions.

IgG3 is very effective at engaging effector mechanisms, such as complement activation, opsonization, neutralization, and antibody-dependent cellular cytotoxicity (ADCC) . IgG3 has a high affinity for the Fc receptors on phagocytes and natural killer (NK) cells, which mediate these functions. IgG3 also has a high affinity for the neonatal Fc receptor (FcRn), which protects it from degradation and prolongs its half-life in serum.

IgG3 has been associated with enhanced control or protection against a range of intracellular bacteria, parasites, and viruses. For example, IgG3 antibodies against Plasmodium falciparum merozoite surface protein 1 (MSP1) have been shown to inhibit parasite growth and invasion in vitro. IgG3 antibodies against Mycobacterium tuberculosis antigens have been correlated with protection against tuberculosis in humans. IgG3 antibodies against human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120) have been linked to reduced viral load and disease progression in infected individuals.

However, IgG3 also has some limitations and challenges. Depending on the allotype of IgG3, its half-life can vary from 7 to 21 days, which is considerably less than that of other IgG subclasses. IgG3 is also more prone to degradation by proteases and oxidation by reactive oxygen species (ROS) due to its long hinge region. Moreover, IgG3 can induce excessive inflammation and tissue damage by activating the complement system or triggering ADCC. Therefore, understanding the molecular and functional properties of IgG3 may facilitate the development of improved antibody-based immunotherapies and vaccines against infectious diseases.

IgG4 is the least common of the four IgG subclasses, comprising usually less than 4% of total IgG. Unlike IgG1, IgG2 and IgG3, IgG4 does not bind to polysaccharides, and has a lower affinity for complement and Fc receptors. IgG4 also has a unique feature of exchanging half-molecules with other IgG4 molecules, resulting in bispecific antibodies that can bind to two different antigens.

IgG4 is involved in several diseases, both autoimmune and infectious. One of the most important diseases associated with IgG4 is IgG4-related disease (IgG4-RD), a chronic inflammatory condition characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, various degrees of fibrosis (scarring) and a usually prompt response to oral steroids. IgG4-RD can affect multiple organs and tissues, such as the pancreas, bile ducts, salivary glands, kidneys, lungs, thyroid gland, aorta, meninges and retroperitoneal tissue . The exact cause of IgG4-RD is unknown, but it likely involves a problem with the immune system. Some of the symptoms of IgG4-RD include swollen lymph nodes, weight loss, jaundice, dry mouth and eyes, abdominal pain and organ enlargement.

Another disease associated with IgG4 is pemphigus, an autoimmune blistering disorder of the skin and mucous membranes. Pemphigus is caused by autoantibodies that target desmosomal proteins that hold epithelial cells together. There are different types of pemphigus, but the most common one is pemphigus vulgaris, which is mainly mediated by IgG4 antibodies. Pemphigus vulgaris causes painful blisters and erosions on the skin and mucous membranes, especially in the mouth, nose, throat and genitals.

Other diseases that have been linked to IgG4 include bullous pemphigoid, another autoimmune blistering disorder of the skin; idiopathic membranous glomerulonephritis, a kidney disease that causes proteinuria and nephrotic syndrome; myasthenia gravis, a neuromuscular disorder that causes muscle weakness; and some helminth infections, such as schistosomiasis and filariasis. In addition, some studies have shown that elevated serum levels of IgG4 are found in patients suffering from sclerosing pancreatitis, cholangitis and interstitial pneumonia caused by infiltrating IgG4 positive plasma cells. The precise role of IgG4 in these diseases is still mostly unknown.

Immunoglobulin G (IgG) is the most abundant and versatile antibody class in the human body. It has various functions that help protect us from infections and diseases. Some of the main functions of IgG are:

• Neutralization: IgG can bind to toxins, viruses and bacteria and prevent them from entering or damaging our cells. This process is called neutralization and it reduces the harmful effects of these foreign substances.
• Opsonization: IgG can coat the surface of pathogens and make them more recognizable by phagocytes, such as macrophages and neutrophils. These cells can then engulf and destroy the opsonized pathogens more efficiently. This process is called opsonization and it enhances the clearance of microbes from our body.
• Complement activation: IgG can trigger a cascade of reactions involving a group of proteins called complement. Complement can help in opsonization, inflammation, lysis and removal of pathogens. This process is called complement activation and it amplifies the immune response against invaders.
• Antibody-dependent cellular cytotoxicity (ADCC): IgG can bind to the surface of infected or abnormal cells, such as cancer cells or virus-infected cells. This can attract natural killer (NK) cells, which can recognize the Fc portion of IgG and release substances that kill the target cells. This process is called ADCC and it eliminates cells that pose a threat to our health.
• Placental transfer: IgG is the only antibody class that can cross the placenta from the mother to the fetus. This provides passive immunity to the newborn and protects it from infections during the first months of life. This process is called placental transfer and it confers maternal antibodies to the offspring.

These are some of the major functions of IgG that illustrate its importance in our immune system. In the next section, we will discuss some of these functions in more detail.

One of the most important functions of Immunoglobulin G (IgG) is to provide protection against pathogens and toxins that circulate in the blood and other body fluids. IgG is the most abundant immunoglobulin in the serum, accounting for about 75% of the total immunoglobulin pool. IgG is also present in the extracellular fluid, which is the fluid that surrounds the cells and tissues. IgG can bind to antigens that are soluble or membrane-bound, and initiate various immune responses to eliminate them.

IgG has several advantages over other immunoglobulins in terms of its ability to control infection of body tissues. First, IgG has a long half-life of about 21 days, which means it can persist in the circulation for a long time and provide lasting immunity. Second, IgG can cross the walls of blood vessels and reach the interstitial spaces where many pathogens and toxins reside. Third, IgG can cross the placenta and confer passive immunity to the fetus and newborn. Fourth, IgG can activate the complement system, which is a cascade of proteins that enhance the killing of microbes and promote inflammation. Fifth, IgG can opsonize pathogens and toxins, which means it can coat them with antibodies and make them more recognizable and digestible by phagocytes. Sixth, IgG can neutralize pathogens and toxins by blocking their ability to bind to receptors or enter cells.

IgG plays a crucial role in the humoral immune response, which is the branch of adaptive immunity that involves antibodies. The humoral immune response consists of two phases: the primary response and the secondary response. The primary response occurs when an antigen is encountered for the first time by naive B cells, which are B cells that have not been exposed to antigens before. Naive B cells differentiate into plasma cells and memory B cells upon activation by antigens and helper T cells. Plasma cells secrete antibodies, mainly IgM and IgG, into the blood and extracellular fluid. Memory B cells remain in a dormant state until they encounter the same antigen again. The secondary response occurs when an antigen is encountered for the second time by memory B cells, which are B cells that have been exposed to antigens before. Memory B cells rapidly differentiate into plasma cells and secrete large amounts of IgG antibodies with high affinity and specificity for the antigen. The secondary response is faster, stronger and more durable than the primary response.

IgG is essential for maintaining health and preventing disease. IgG protects against a wide range of pathogens and toxins, such as bacteria, viruses, fungi, parasites and venom. IgG also mediates allergic reactions, autoimmune diseases and transplant rejection by binding to self-antigens or foreign antigens on host cells. IgG levels can be used as an indicator of past or current infection or vaccination. Detection of specific IgG antibodies can help diagnose various infectious diseases, such as hepatitis, HIV, measles, rubella and syphilis. IgG can also be used for passive immunization by transferring this antibody from an immune donor to a non-immune recipient. Passive immunization can provide immediate protection against certain diseases, such as tetanus, rabies and snake bites.

One of the most remarkable features of IgG is its ability to cross the placenta in humans and provide passive immunity to the fetus and newborn. This is possible because of a specialized receptor called FcRn (neonatal Fc receptor) that is expressed on the placental trophoblasts and binds to IgG with high affinity at acidic pH. The FcRn transports IgG from the maternal circulation to the fetal circulation by transcytosis, a process that involves endocytosis, vesicular transport and exocytosis. The FcRn also protects IgG from degradation by lysosomal enzymes in the endosomes.

The transfer of IgG across the placenta begins around the 12th week of gestation and increases progressively until term. The concentration of IgG in the fetal serum is usually equal to or higher than that in the maternal serum by the third trimester. The IgG subclasses that are most efficiently transferred are IgG1 and IgG3, followed by IgG4 and IgG2. The transferred IgG confers protection to the fetus and newborn against various pathogens, especially those that cause respiratory and gastrointestinal infections. The passive immunity provided by maternal IgG lasts for several months after birth, until the infant`s own immune system matures and produces its own antibodies.

The ability of IgG to cross the placenta is unique among human immunoglobulins and is not shared by other classes such as IgM, IgA or IgE. This is because these immunoglobulins are either too large, have different Fc regions or are actively excluded by the placenta. However, some animal species have different mechanisms of transferring maternal antibodies to their offspring, such as through colostrum (the first milk produced by mammals), egg yolk (in birds and reptiles) or skin secretions (in amphibians and fish).

The humoral immune response is one of the two types of adaptive immune responses that defend against pathogens that are free in the blood and lymph. It involves mainly B cells that produce antibodies against specific antigens. IgG is the major immunoglobulin in the humoral immune response and has several functions to eliminate pathogens and prevent infections.

One of the functions of IgG is to bind to antigens on the surface of pathogens and mark them for destruction by phagocytic cells, such as macrophages and neutrophils, in a process called opsonization . Opsonization enhances the recognition and ingestion of pathogens by phagocytes and thus clears them from the body.

Another function of IgG is to neutralize pathogens by coating key sites that are necessary for infection, such as toxins, receptors, or enzymes . Neutralization prevents pathogens from attaching to host cells or entering them, and also blocks their harmful effects on host tissues.

A third function of IgG is to activate the complement system, which is a cascade of proteins that amplify the immune response and cause inflammation, lysis, or opsonization of pathogens . IgG can trigger the complement system by binding to antigens on pathogens and forming antigen-antibody complexes that initiate a series of reactions involving complement proteins.

By performing these functions, IgG plays a vital role in the humoral immune response and contributes to the protection and recovery of the host from infections.

Opsonization is a process that enhances the phagocytosis of pathogens by coating them with molecules that bind to receptors on phagocytes. One of the most important opsonins is immunoglobulin G (IgG), a type of antibody that is produced by plasma cells in response to specific antigens. IgG antibodies have two antigen-binding sites at the tips of their Y-shaped structure, which can recognize and bind to epitopes on the surface of pathogens. The stem region of IgG, also known as the Fc portion, can then bind to Fc receptors on phagocytes such as macrophages and neutrophils. This creates a bridge between the pathogen and the phagocyte, facilitating the engulfment and destruction of the pathogen by the phagocyte.

IgG can also activate the complement system, a cascade of proteins that can enhance the opsonization and lysis of pathogens. IgG can bind to C1q, the first component of the classical complement pathway, which then triggers a series of reactions that result in the cleavage of C3 and C4 into C3b and C4b. These fragments can attach to the surface of pathogens and act as opsonins by binding to complement receptors on phagocytes. C3b and C4b can also form a complex with other complement proteins that can insert into the membrane of pathogens and form pores, leading to osmotic lysis.

Opsonization by IgG is an important mechanism that helps the immune system to eliminate pathogens more efficiently and prevent infections. IgG can also cross the placenta and provide passive immunity to newborns. However, some pathogens have evolved strategies to evade opsonization by IgG, such as producing capsules, proteases, or antigenic variation. Therefore, opsonization by IgG is not sufficient to protect against all types of pathogens, and other immune responses are also required.

One of the remarkable features of IgG is its long half-life in serum, which ranges from 7 to 23 days depending on the subclass. This means that IgG can persist in the body for a long time after an infection or vaccination, providing lasting protection against pathogens. IgG is also the most abundant immunoglobulin in colostrum and breast milk, which confers passive immunity to newborns.

Passive immunization is the transfer of preformed antibodies from an immune individual to a non-immune or susceptible individual. This can be done by injecting purified IgG antibodies or plasma containing IgG antibodies into the recipient. Passive immunization can provide immediate protection against a specific pathogen or toxin, but it does not induce memory or long-term immunity.

Passive immunization has been used for various purposes, such as:

• Prevention or treatment of infectious diseases, such as tetanus, rabies, hepatitis B, botulism, diphtheria and snake venom poisoning .
• Treatment of autoimmune diseases, such as idiopathic thrombocytopenic purpura (ITP), Guillain-Barré syndrome and myasthenia gravis .
• Treatment of immunodeficiency disorders, such as primary immunodeficiency (PID), acquired immunodeficiency syndrome (AIDS) and severe combined immunodeficiency (SCID) .
• Modulation of immune responses in transplantation, allergy and cancer .

Passive immunization has some limitations and risks, such as:

• The availability and cost of IgG antibodies or plasma sources.
• The possibility of adverse reactions, such as allergic reactions, serum sickness and transmission of infectious agents .
• The interference with active immunization by suppressing the recipient`s own immune response .
• The short duration of protection compared to active immunization .

Therefore, passive immunization is usually considered as a temporary or complementary measure to active immunization or other therapeutic interventions.

In summary, IgG is a versatile and durable antibody that plays a vital role in humoral immunity and passive immunization. Its longevity in serum allows it to provide long-term protection against pathogens and to be used as a source of antibodies for passive immunization. However, passive immunization has some limitations and risks that need to be weighed against its benefits.

Immunoglobulin G (IgG) is the most abundant and versatile antibody class in human serum. It has a complex structure composed of four subclasses, each with different properties and functions. IgG antibodies protect the body from various pathogens by binding to antigens, forming immune complexes, activating complement, triggering effector cells, and crossing the placenta. IgG antibodies also play a role in the humoral immune response and opsonization. IgG subclass deficiency is a condition where one or more IgG subclasses are low or absent, but total IgG is normal. This can increase the risk of infections, especially by bacteria. IgG subclass imbalance is also associated with several autoimmune, infectious and metabolic diseases . Therefore, IgG subclasses are important biomarkers for diagnosis and prognosis of various disorders. IgG is also widely used in immunological research and clinical diagnostics because of its abundance and specificity. In summary, IgG is a vital component of the immune system that provides protection and regulation against various challenges.

We are Compiling this Section. Thanks for your understanding.