Antibody- Introduction, Structure and Classes

Antibodies are essential components of the adaptive immune system, which is the branch of immunity that can recognize and eliminate specific pathogens and foreign substances. The adaptive immune system consists of two types of lymphocytes: B cells and T cells. B cells are responsible for producing and secreting antibodies, while T cells help to activate B cells and other immune cells.

Antibodies are also known as immunoglobulins (Ig), which means immune proteins. They are Y-shaped molecules that consist of four polypeptide chains: two identical heavy chains and two identical light chains. The chains are held together by disulfide bonds and non-covalent interactions. Each antibody has two antigen-binding sites, one at the tip of each arm of the Y. The antigen-binding sites are formed by the variable regions of the heavy and light chains, which can vary in their amino acid sequences among different antibodies. The variable regions are responsible for recognizing and binding to specific antigens, which are molecules that can elicit an immune response. Antigens can be proteins, polysaccharides, lipids, nucleic acids, or other substances that are foreign to the body.

The stem of the Y-shaped antibody is formed by the constant regions of the heavy chains, which do not vary among antibodies of the same class or isotype. The constant regions determine the biological functions of the antibodies, such as activating complement proteins, binding to Fc receptors on immune cells, or crossing biological barriers. There are five main classes or isotypes of antibodies in humans: IgM, IgG, IgA, IgE, and IgD. Each class has different physical and biological properties that suit different roles in immunity.

Antibodies play a crucial role in defending the body against infections and diseases. They can neutralize toxins, prevent viruses from entering cells, opsonize bacteria for phagocytosis, activate complement system for lysis, or trigger antibody-dependent cellular cytotoxicity (ADCC) by natural killer cells. Antibodies can also mediate allergic reactions, autoimmune disorders, and transplant rejection by binding to self-antigens or foreign antigens on host cells.

Antibodies are produced by B cells in response to antigen stimulation. B cells undergo a process of maturation and differentiation in the bone marrow and peripheral lymphoid organs, such as the spleen and lymph nodes. During this process, B cells rearrange their immunoglobulin genes to generate a diverse repertoire of antibodies with different antigen specificities. B cells also undergo somatic hypermutation and class switch recombination to improve their affinity and change their isotype. Some B cells become plasma cells that secrete large amounts of antibodies into the blood and lymph. Other B cells become memory cells that persist in the body and provide long-lasting immunity.

Antibodies are remarkable molecules that can adapt to various challenges posed by pathogens and foreign substances. They are indispensable for the protection and regulation of the immune system. In this article, we will explore the structure and classes of antibodies in more detail.

Immunoglobulins, also known as antibodies, are a class of proteins that are produced by plasma cells in response to specific antigens. Antigens are foreign substances, such as bacteria, viruses, toxins, or pollen, that stimulate the immune system to produce antibodies. Antibodies recognize and bind to antigens, and help to eliminate them from the body.

Immunoglobulins are composed of two identical heavy chains and two identical light chains, which are linked by disulfide bonds. Each chain has a variable region (V) and a constant region (C). The variable regions of the heavy and light chains form the antigen-binding site, which is specific for each antibody. The constant regions of the heavy chains determine the class or isotype of the antibody, and mediate various biological functions.

There are five major classes or isotypes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM. Each class has different properties and functions in the immune system. IgA is mainly found in mucosal secretions, such as saliva, tears, and breast milk, and protects against infections at the body surfaces. IgD is mainly expressed on the surface of B cells, and serves as a receptor for antigen activation. IgE is involved in allergic reactions and parasitic infections, and binds to mast cells and basophils. IgG is the most abundant and versatile class of immunoglobulins, and can cross the placenta to provide passive immunity to the fetus. IgM is the first antibody produced in response to an infection, and activates the complement system.

Immunoglobulins play a crucial role in the humoral immune response, which is one of the main mechanisms of adaptive immunity. By binding to antigens, immunoglobulins can neutralize toxins, prevent viral entry into cells, opsonize pathogens for phagocytosis, activate complement-mediated lysis, or recruit other immune cells for antibody-dependent cellular cytotoxicity (ADCC). Immunoglobulins also provide immunological memory, which allows for a faster and stronger response upon re-exposure to the same antigen.

Antibodies are Y-shaped molecules that consist of four polypeptide chains: two identical heavy chains and two identical light chains. The heavy chains and light chains are held together by disulfide bonds and non-covalent interactions. 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 site, which is specific for a particular antigen. The C regions of the heavy chains determine the class (or isotype) of the antibody and mediate various effector functions.

The basic structure of an antibody molecule can be represented as follows:

The V regions of the heavy and light chains are composed of Ig domains, which are globular units of about 110 amino acids that fold into a characteristic beta-sandwich structure. The V regions contain three hypervariable regions (or complementarity-determining regions, CDRs) that form loops on the surface of the Ig domain and confer antigen specificity. The CDRs are flanked by four framework regions (FRs) that provide structural stability.

The C regions of the heavy and light chains are also composed of Ig domains, but they are less variable than the V regions. The C regions of the light chains have only one Ig domain each, whereas the C regions of the heavy chains have three or four Ig domains depending on the class of the antibody. The C regions of the heavy chains also have a hinge region between the first and second Ig domains, which provides flexibility to the antibody molecule.

The antigen-binding site of an antibody is formed by the combination of the V regions of one heavy chain and one light chain. Each antibody molecule has two identical antigen-binding sites, which can recognize and bind to two antigens at the same time. The antigen-binding site is shaped by the CDRs, which form a complementary surface to the antigen. The antigen can be a protein, a polysaccharide, a lipid, or any other molecule that can elicit an immune response.

The Fc region of an antibody is formed by the C regions of both heavy chains. The Fc region does not bind to antigens, but it interacts with other molecules and cells of the immune system to mediate various effector functions. For example, the Fc region can bind to Fc receptors on phagocytes, natural killer cells, mast cells, or basophils, and trigger their activation or degranulation. The Fc region can also bind to complement proteins and initiate a cascade of reactions that leads to opsonization, inflammation, or lysis of pathogens.

The structure of antibodies is highly diverse and adaptable, allowing them to recognize and eliminate a wide range of antigens. The structure also determines the class and function of antibodies, which have different roles in different types of immune responses. Understanding the structure of antibodies is essential for understanding how they work in immunity and how they can be used in diagnostics, therapeutics, and research.

An antibody molecule has a symmetric core structure composed of two identical light chains and two identical heavy chains. Both the light chains and heavy chains contain a series of repeating homologous units, each about 110 amino acid residues in length, that fold independently in a globular motif that is called an Ig domain. In the heavy chains, the V region is composed of one Ig domain, and the C region is composed of three or four Ig domains. Each light chain is composed of one V region Ig domain and one C region Ig domain. The N-terminal half of light chains is thus referred to as the variable, or VL, the region of the light chain, and the less variable part of the sequence is termed the constant, or CL, region. The two major light chain constant region sequences are referred to as k (kappa) or λ (lambda) chains. As more light-chain sequences were generated, it became apparent that the lambda chain constant region sequences could be further subdivided into four subtypes—λ 1, λ 2, λ 3, and λ 4—based on amino acid substitutions at a few positions. In humans, the light chains are fairly evenly divided between the two light-chain classes; 60% of human light chains are kappa whereas only 40% are lambda. In mice, the situation is quite different: Only 5% of mouse light chains are of the lambda light-chain type. All light chains have a molecular weight of approximately 22 kDa.

Heavy and light chains are covalently linked by disulfide bonds formed between cysteine residues in the carboxy terminus of the light chain and the CH1 domain of the heavy chain. Non-covalent interactions between the VL and VH domains and between the CL and CH1 domains may also contribute to the association of heavy and light chains. The two heavy chains of each antibody molecule are covalently linked by disulfide bonds. In IgG antibodies, these bonds are formed between cysteine residues in the CH2 domains, close to the region known as the hinge. In other isotypes, the disulfide bonds may be in different locations. Non-covalent interactions (e.g., between the third CH domains ) may also contribute to heavy chain pairing.

The heavy chain C regions interact with other effector molecules and cells of the immune system and therefore mediate most of the biologic functions of antibodies. In addition, heavy chains exist in two forms that differ at their carboxy-terminal ends: one form of the heavy chain anchors membrane-bound antibodies in the plasma membranes of B lymphocytes, and the other form is found only in secreted antibodies. The C regions of light chains do not participate in effector functions and are not directly attached to cell membranes.

The length of the constant region of the heavy chains is either 330 amino acid residues (for γ, 𝛿, and α chains) or 440 amino acids (for μ and ε chains). Correspondingly, the molecular weights of the heavy chains vary according to their class. IgA, IgD, and IgG heavy chains weigh approximately 55 kDa, whereas IgM and IgE antibodies are approximately 20% heavier.

Using antibodies directed toward the constant region of immunoglobulins and amino acid sequencing of immunoglobulins derived from plasmacytoma tumor cells, investigators discovered that the sequences of the heavy-chain constant regions fall into five basic patterns. These five basic sequences have been named with Greek letters: μ (mu), 𝛿 (delta), γ (gamma), ε (epsilon), and α (alpha). Each different heavy-chain constant region is referred to as an isotype, and the isotype of the heavy chains of a given antibody molecule determines its class. Thus, antibodies with a heavy chain of the μ isotype are of the IgM class; those with a 𝛿 heavy chain are IgD; those with γ, IgG; those with ε, IgE; and those with α, IgA.

The variable (V) regions and constant (C) regions are two types of domains that make up the immunoglobulin (Ig) domains. Ig domains are globular motifs of about 110 amino acid residues that fold independently and have a characteristic structure. Each Ig domain consists of two β sheets that are held together by a disulfide bond between two cysteine residues. The β sheets form a sandwich-like structure with a hydrophobic core and a hydrophilic surface.

The V regions are the domains that participate in antigen recognition and binding. They are located at the N-terminal end of both the heavy and light chains. The V regions are highly variable in their amino acid sequences among different antibodies, which allows them to recognize a diverse range of antigens. The V regions are composed of one Ig domain each in the heavy and light chains.

The C regions are the domains that mediate the effector functions of antibodies, such as complement activation, opsonization, antibody-dependent cellular cytotoxicity (ADCC), and placental transfer. They are located at the C-terminal end of both the heavy and light chains. The C regions are relatively conserved in their amino acid sequences among different antibodies, which allows them to interact with other molecules and cells of the immune system. The C regions are composed of three or four Ig domains in the heavy chains and one Ig domain in the light chains.

The V regions and C regions are connected by flexible linker sequences that allow the antibody molecule to adopt different conformations and orientations. The linker sequences also contain sites for proteolytic cleavage by enzymes such as papain and pepsin, which can generate different antibody fragments with distinct functions.

Disulfide bonds are covalent bonds formed by the oxidation of two cysteine residues in proteins. They play an important role in stabilizing the tertiary structure and function of proteins, especially those that are secreted or exposed to the extracellular environment. Antibodies, as a type of immunoglobulins (immune proteins), contain a number of disulfide bonds that link the heavy and light chains, as well as the domains within each chain.

As shown in Figure 1, a typical IgG antibody has six intra-domain disulfide bonds: two in each heavy chain and one in each light chain. These bonds are located between conserved cysteine residues within the Ig domains and help to maintain the globular shape of each domain. In addition, there are four inter-domain disulfide bonds: two between the heavy and light chains, and two between the two heavy chains. These bonds are formed between cysteine residues in the CH1 and CL domains, and in the CH2 domains near the hinge region, respectively. The inter-domain disulfide bonds hold the antibody molecule together and allow some flexibility for antigen binding.

Disulfide bond formation is a post-translational modification that occurs in the endoplasmic reticulum (ER) of B cells, where antibodies are synthesized. The ER provides an oxidative environment that favors disulfide bond formation, as well as enzymes that catalyze and regulate this process. Disulfide bond formation is essential for proper folding, assembly, secretion and stability of antibodies. Disulfide bond reduction, on the other hand, can lead to loss of antibody structure and function, decreased product purity and quality, and potential safety and efficacy issues. Therefore, it is important to prevent or minimize disulfide bond reduction during antibody biopharmaceutical process development and manufacturing.

One of the most remarkable features of antibodies is their ability to recognize a vast array of antigens with high specificity and affinity. This diversity is generated by the variability in the amino acid sequences of the antigen-binding sites of antibodies, which are located at the tips of the Y-shaped molecules. The antigen-binding site is formed by the combination of the variable (V) regions of the heavy and light chains, each of which has three short stretches of amino acids that are highly variable among different antibodies. These segments are called hypervariable regions or complementarity-determining regions (CDRs) because they form a surface that is complementary to the shape of the bound antigen.

The hypervariable regions are not randomly distributed along the V regions, but are clustered in three loops at the N-terminal end of each domain. The three hypervariable regions of the heavy chain (H1, H2, and H3) and the three hypervariable regions of the light chain (L1, L2, and L3) come together to form a pocket or a groove that can accommodate the antigen. The antigen-binding site can be thought of as a lock that recognizes a specific key (the antigen). The shape and size of the antigen-binding site can vary depending on the nature of the antigen, which can be a small molecule, a peptide, a protein, a carbohydrate, or a lipid.

The hypervariable regions are responsible for most of the sequence differences and variability among different antibodies. They are generated by a process of somatic recombination and mutation that occurs during B cell development and activation. The diversity and specificity of antibodies depend largely on the diversity and specificity of the hypervariable regions. By changing the amino acid sequences of these regions, antibodies can adapt to recognize new or modified antigens that may arise during infection or immunization.

The complementarity determining regions (CDRs) are the parts of the antibody that directly interact with the antigen. They are also called hypervariable regions because they have the highest variability in amino acid sequence among different antibodies. There are three CDRs in each variable region of the heavy and light chains, making a total of six CDRs per antigen-binding site. The CDRs are located at the tips of the loops that protrude from the beta sheets of the variable domains. The loops are numbered from L1 to L3 for the light chain and from H1 to H3 for the heavy chain.

The CDRs are responsible for the specificity and diversity of antibodies. They form a three-dimensional surface that is complementary to the shape and charge of the antigen. The CDRs can recognize a wide range of antigens, such as proteins, polysaccharides, lipids, nucleic acids, and small molecules. The CDRs can also accommodate different types of antigen-binding modes, such as lock-and-key, induced fit, and multivalent binding.

The CDRs are generated by a process called somatic recombination, which occurs during the development of B cells in the bone marrow. Somatic recombination involves the random joining of gene segments called variable (V), diversity (D), and joining (J) segments to form a functional V region gene. The VDJ recombination results in a large number of possible combinations of gene segments, which contribute to the diversity of the CDRs. In addition, somatic hypermutation introduces point mutations in the V region genes after antigen stimulation, which further increases the variability and affinity of the CDRs.

The CDRs are also subject to structural constraints that limit their variability. For example, some amino acids are more common than others in certain positions of the CDRs, and some positions are more conserved than others. The structural constraints ensure that the CDRs maintain their stability and folding, as well as their compatibility with the constant regions of the antibody.

The CDRs are essential for the function and evolution of antibodies. They enable antibodies to recognize and bind to a vast array of antigens with high specificity and affinity. They also allow antibodies to adapt to changing antigens by undergoing somatic recombination and hypermutation. The CDRs are therefore the key determinants of the immune response and protection against pathogens.

The hinge region is a short segment of amino acids that connects the Fab and Fc regions of the antibody molecule. The hinge region is located between the CH1 and CH2 domains of the heavy chain and varies in length and composition depending on the antibody class. The hinge region provides flexibility and mobility to the antibody molecule, allowing it to adopt different orientations and conformations to bind to various antigens. The hinge region also facilitates the formation of multivalent antibodies, such as IgM and IgA, by linking two or more heavy chains together.

The hinge region contains many cysteine residues that form disulfide bonds between the heavy chains. These bonds stabilize the structure of the antibody molecule and determine its valency (the number of antigen-binding sites). For example, IgG has one hinge region with two interchain disulfide bonds, resulting in a monomeric antibody with two antigen-binding sites. IgM has four hinge regions with ten interchain disulfide bonds, resulting in a pentameric antibody with ten antigen-binding sites. IgA has three hinge regions with six interchain disulfide bonds, resulting in a dimeric antibody with four antigen-binding sites.

The hinge region is also susceptible to proteolytic cleavage by enzymes such as papain and pepsin. Papain cleaves the antibody molecule above the hinge region, producing two Fab fragments that retain antigen-binding activity and one Fc fragment that mediates effector functions. Pepsin cleaves the antibody molecule below the hinge region, producing one F(ab`)2 fragment that has two antigen-binding sites and one pFc` fragment that is usually degraded. The proteolytic cleavage of antibodies can be useful for studying their structure and function.

The hinge region is also involved in some biological functions of antibodies, such as complement activation and binding to Fc receptors. The hinge region of IgG contains a proline-rich motif that binds to C1q, the first component of the classical complement pathway. The hinge region of IgE contains a hydrophobic motif that binds to FcεRI, a high-affinity receptor for IgE on mast cells and basophils. The hinge region of IgA contains a serine-rich motif that binds to FcαRI, a low-affinity receptor for IgA on phagocytes and epithelial cells.

The hinge region is therefore an important structural and functional feature of antibodies that contributes to their diversity and versatility in immune responses.

The antibody molecule can be divided into two functional regions: the Fab region and the Fc region. The Fab region, which stands for fragment antigen-binding, is composed of the variable domains of both the heavy and light chains, as well as the constant domains of the light chain and the first constant domain of the heavy chain (CH1). The Fab region is responsible for recognizing and binding to the antigen. Each antibody molecule has two identical Fab regions, one at each arm of the Y-shaped structure.

The Fc region, which stands for fragment crystallizable, is composed of the remaining constant domains of the heavy chain (CH2 and CH3, or CH2-CH4 in IgM and IgE). The Fc region does not bind to the antigen, but mediates various effector functions of antibodies, such as opsonization, complement activation, antibody-dependent cellular cytotoxicity (ADCC), and placental transfer. The Fc region also determines the isotype and subclass of the antibody. Different classes and subclasses of antibodies have different Fc regions that can bind to specific Fc receptors on various immune cells. For example, IgG1 and IgG3 can bind to FcγRI on macrophages and activate them to phagocytose the antigen-antibody complex. IgE can bind to FcεRI on mast cells and basophils and trigger degranulation and release of inflammatory mediators.

The Fab region and the Fc region are connected by a flexible hinge region that allows the antibody to adopt different orientations and conformations. The hinge region also contains disulfide bonds that link the two heavy chains together. The hinge region is susceptible to proteolytic cleavage by enzymes such as papain and pepsin. Papain cleaves the antibody above the hinge region, generating two Fab fragments and one Fc fragment. Pepsin cleaves the antibody below the hinge region, generating one F(ab`)2 fragment that retains both antigen-binding sites, and several small Fc fragments that are degraded.

The Fab region and the Fc region of antibodies play complementary roles in mediating immune responses. The Fab region binds to the antigen with high specificity and affinity, while the Fc region interacts with other immune components to elicit various effector functions. Together, they enable antibodies to neutralize, eliminate, or regulate antigens in different ways.

As mentioned earlier, antibodies are classified into five major classes based on the type of heavy chain they have: IgM, IgD, IgG, IgE and IgA. Each class of antibody has distinct features and functions in the immune system. Here is a brief overview of each class:

• IgM: This is the first antibody produced in response to an antigen. It is mainly found in the blood and lymphatic fluid, where it forms pentamers (five antibody molecules joined together). IgM is very effective at activating the complement system, a group of proteins that enhance the immune response. IgM also acts as a receptor for antigens on the surface of B cells, along with IgD.

• IgD: This antibody is mainly found on the surface of B cells, where it serves as a receptor for antigens along with IgM. It is also present in small amounts in the blood and lymphatic fluid. The function of IgD is not fully understood, but it may play a role in regulating B cell activation and differentiation.

• IgG: This is the most abundant and diverse antibody in the blood and extracellular fluid. It can cross the placenta and provide passive immunity to the fetus. It can also bind to Fc receptors on various immune cells and mediate different effector functions, such as opsonization (coating of pathogens for easier phagocytosis), antibody-dependent cellular cytotoxicity (killing of target cells by natural killer cells or macrophages), and neutralization (blocking of toxins or viruses from binding to their receptors). IgG has four subclasses: IgG1, IgG2, IgG3 and IgG4, which differ in their structure and function.

• IgE: This antibody is mainly involved in allergic reactions and parasitic infections. It binds to mast cells and basophils, which are granulocytes that release histamine and other inflammatory mediators when triggered by an antigen. IgE also activates the complement system and attracts eosinophils, which are white blood cells that kill parasites.

• IgA: This antibody is mainly found in mucosal secretions, such as saliva, tears, breast milk, and intestinal fluid. It protects the mucosal surfaces from pathogens by preventing their attachment and invasion. It can also neutralize toxins and viruses in the lumen of the gut. IgA exists as a monomer (single antibody molecule) or a dimer (two antibody molecules joined by a J chain). The dimeric form of IgA can bind to a polymeric immunoglobulin receptor (pIgR) on epithelial cells and be transported across the mucosal barrier.

These are the main classes of immunoglobulins that are involved in humoral immunity. Each class has its own advantages and disadvantages in terms of affinity, specificity, stability, distribution, and effector functions. The diversity and flexibility of antibodies allow them to recognize and eliminate a wide range of antigens. In the next section, we will discuss the physical properties of each immunoglobulin class.

The five classes of immunoglobulins differ not only in their heavy chain constant regions, but also in their physical properties, such as size, shape, valency, and molecular weight. These properties affect the distribution and function of the antibodies in the body.

• IgM is the largest antibody class, with a pentameric structure consisting of five monomers linked by disulfide bonds and a J chain. Each monomer has two antigen-binding sites, so the valency of IgM is 10. The molecular weight of IgM is about 900 kDa. IgM is mainly found in the blood and lymph, where it serves as the first line of defense against pathogens. IgM is also the first antibody class produced during a primary immune response.

• IgG is the most abundant and diverse antibody class, with four subclasses: IgG1, IgG2, IgG3, and IgG4. Each subclass has a slightly different heavy chain constant region and biological function. IgG has a monomeric structure with two antigen-binding sites, so its valency is 2. The molecular weight of IgG is about 150 kDa. IgG is widely distributed in the blood, lymph, and tissues, where it provides long-term protection against pathogens. IgG can also cross the placenta and provide passive immunity to the fetus.

• IgA is the main antibody class found in mucosal secretions, such as saliva, tears, breast milk, and intestinal fluids. IgA has two subclasses: IgA1 and IgA2. Each subclass has a slightly different heavy chain constant region and susceptibility to proteases. IgA can exist as a monomer or a dimer. The dimeric form is more common in secretions and is linked by a J chain and a secretory component. Each monomer has two antigen-binding sites, so the valency of dimeric IgA is 4. The molecular weight of monomeric IgA is about 160 kDa, and that of dimeric IgA is about 385 kDa. IgA protects the mucosal surfaces from pathogens and prevents their adherence and invasion.

• IgE is the least abundant antibody class, with a monomeric structure and two antigen-binding sites. The molecular weight of IgE is about 190 kDa. IgE is mainly found bound to mast cells and basophils in the skin and mucosal tissues. IgE mediates allergic reactions and immunity against parasites by triggering the release of histamine and other inflammatory mediators from these cells.

• IgD is a poorly understood antibody class, with a monomeric structure and two antigen-binding sites. The molecular weight of IgD is about 180 kDa. IgD is mainly found on the surface of naive B cells, where it serves as a co-receptor with IgM for antigen recognition and activation.

  Biological Properties of Major Ig

The five primary classes of immunoglobulins are IgG, IgM, IgA, IgD, and IgE. These are distinguished by the type of heavy chain found in the molecule. Each class has different biological properties that determine their roles in immune responses. Here is a summary of the main biological properties of each class:

IgG

IgG is the main type of antibody found in blood and extracellular fluid, allowing it to control infection of body tissues. It has four subclasses: IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties. By binding many kinds of pathogens such as viruses, bacteria, and fungi, IgG protects the body from infection. Some of the functions of IgG are:

• It mediates the secondary response, which is faster and stronger than the primary response mediated by IgM.
• It opsonizes pathogens, which means it coats them with antibodies to enhance their phagocytosis by macrophages and neutrophils.
• It activates the complement system, which is a cascade of proteins that can lyse pathogens or mark them for phagocytosis.
• It crosses the placenta and provides passive immunity to the fetus and newborn.
• It binds to Fc receptors on natural killer cells and mediates antibody-dependent cellular cytotoxicity (ADCC), which is a process of killing target cells coated with antibodies.

IgM

IgM is the largest antibody molecule and the first antibody to appear in response to an initial exposure to an antigen. It is mainly found in the intravascular space. It forms pentamers of five identical units linked by a J chain. Some of the functions of IgM are:

• It mediates the primary response, which is slower and weaker than the secondary response mediated by IgG.
• It activates the complement system more efficiently than any other class of immunoglobulins.
• It agglutinates pathogens, which means it clumps them together to prevent their spread and facilitate their clearance.

IgA

IgA is the most abundant antibody in mucosal secretions such as saliva, tears, milk, and intestinal fluids. It has two subclasses: IgA1 and IgA2. It can exist as a monomer or as a dimer of two identical units linked by a J chain. Some of the functions of IgA are:

• It provides mucosal immunity by preventing the attachment of pathogens to epithelial cells and neutralizing their toxins.
• It protects the newborn from gastrointestinal infections by being present in colostrum and breast milk.

IgD

IgD is a monomeric antibody that is mainly found on the surface of mature B cells along with IgM. It has a very low serum concentration and a short half-life. Its function is not fully understood, but it may play a role in:

• B cell activation by binding to antigens and inducing proliferation and differentiation.
• B cell tolerance by deleting self-reactive B cells.

IgE

IgE is a monomeric antibody that has a very low serum concentration and a short half-life. It binds with high affinity to Fc receptors on mast cells and basophils. Its function is mainly involved in:

• Allergic reactions by triggering the release of histamine and other inflammatory mediators from mast cells and basophils upon exposure to allergens.
• Immunity to parasites by coating them with antibodies and activating eosinophils and mast cells to kill them.

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