Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. [1] IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes.
Antibodies are major components of humoral immunity. IgG is the main type of antibody found in blood and extracellular fluid, allowing it to control infection of body tissues. By binding many kinds of pathogens such as viruses, bacteria, and fungi, IgG protects the body from infection.[ citation needed ]
It does this through several mechanisms:[ citation needed ]
IgG antibodies are generated following class switching and maturation of the antibody response, thus they participate predominantly in the secondary immune response. [3]
IgG is secreted as a monomer that is small in size allowing it to easily diffuse into tissues. It is the only antibody isotype that has receptors to facilitate passage through the human placenta, thereby providing protection to the fetus in utero . Along with IgA secreted in the breast milk, residual IgG absorbed through the placenta provides the neonate with humoral immunity before its own immune system develops. Colostrum contains a high percentage of IgG, especially bovine colostrum. In individuals with prior immunity to a pathogen, IgG appears about 24–48 hours after antigenic stimulation.[ citation needed ]
Therefore, in the first six months of life, the newborn has the same antibodies as the mother and the child can defend itself against all the pathogens that the mother encountered in her life (even if only through vaccination) until these antibodies are degraded. This repertoire of immunoglobulins is crucial for the newborns who are very sensitive to infections, especially within the respiratory and digestive systems.[ citation needed ]
IgG are also involved in the regulation of allergic reactions. According to Finkelman, there are two pathways of systemic anaphylaxis: [4] [5] antigens can cause systemic anaphylaxis in mice through classic pathway by cross-linking IgE bound to the mast cell receptor FcεRI, stimulating the release of both histamine and platelet activating factor (PAF). In the alternative pathway, antigens form complexes with IgG, which then cross-link macrophage receptor FcγRIII and stimulates only PAF release. [4]
IgG antibodies can prevent IgE mediated anaphylaxis by intercepting a specific antigen before it binds to mast cell–associated IgE. Consequently, IgG antibodies block systemic anaphylaxis induced by small quantities of antigen but can mediate systemic anaphylaxis induced by larger quantities. [4]
IgG antibodies are large globular proteins made of four peptide chains; [6] two identical γ (gamma) heavy chains of about 50 kDa and two identical light chains of about 25 kDa. The resulting tetrameric quaternary structure, therefore, has a total molecular weight of about 150 kDa. [7] The two heavy chains are linked to each other and to a light chain each by disulfide bonds. The resulting tetramer has two identical halves, which together form a Y-like shape. Each end of the fork contains an identical antigen binding site. The various regions and domains of a typical IgG are depicted in the figure "Anatomy of an IgG".
The Fc regions of IgGs bear a highly conserved N-glycosylation site at asparagine 297 in the constant region of the heavy chain. [8] The N-glycans attached to this site are predominantly core-fucosylated biantennary structures of the complex type. [9] In addition, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6-linked sialic acid residues. [10] The N-glycan composition in IgG has been linked to several autoimmune, infectious and metabolic diseases. [11]
There are four IgG subclasses (IgG1, 2, 3, and 4) in humans, named in order of their abundance in serum (IgG1 being the most abundant). [12]
| Name | Percentage | Crosses placenta easily | Complement activator | Binds to Fc receptor on phagocytic cells | Half life [13] |
|---|---|---|---|---|---|
| IgG1 | 66% | yes (1.47)* | second-highest | high affinity | 21 days |
| IgG2 | 23% | no (0.8)* | third-highest | extremely low affinity | 21 days |
| IgG3 | 7% | yes (1.17)* | highest | high affinity | 7 days |
| IgG4 | 4% | yes (1.15)* | no | intermediate affinity | 21 days |
| * Quota cord/maternity concentrations blood. Based on data from a Japanese study on 228 mothers. [14] | |||||
Note: IgG affinity to Fc receptors on phagocytic cells is specific to individual species from which the antibody comes as well as the class. The structure of the hinge regions (region 6 in the diagram) contributes to the unique biological properties of each of the four IgG classes. Even though there is about 95% similarity between their Fc regions, the structure of the hinge regions is relatively different.[ citation needed ]
Given the opposing properties of the IgG subclasses (fixing and failing to fix complement; binding and failing to bind FcR), and the fact that the immune response to most antigens includes a mix of all four subclasses, it has been difficult to understand how IgG subclasses can work together to provide protective immunity. In 2013, the Temporal Model of human IgE and IgG function was proposed. [15] This model suggests that IgG3 (and IgE) appear early in a response. The IgG3, though of relatively low affinity, allows IgG-mediated defences to join IgM-mediated defences in clearing foreign antigens. Subsequently, higher affinity IgG1 and IgG2 are produced. The relative balance of these subclasses, in any immune complexes that form, helps determine the strength of the inflammatory processes that follow. Finally, if antigen persists, high affinity IgG4 is produced, which dampens down inflammation by helping to curtail FcR-mediated processes.[ citation needed ]
The relative ability of different IgG subclasses to fix complement may explain why some anti-donor antibody responses do harm a graft after organ transplantation. [16]
In a mouse model of autoantibody mediated anemia using IgG isotype switch variants of an anti erythrocytes autoantibody, it was found that mouse IgG2a was superior to IgG1 in activating complement. Moreover, it was found that the IgG2a isotype was able to interact very efficiently with FcgammaR. As a result, 20 times higher doses of IgG1, in relationship to IgG2a autoantibodies, were required to induce autoantibody mediated pathology. [17] Since mouse IgG1 and human IgG1 are not entirely similar in function, and the inference of human antibody function from mouse studies must be done with great care. However, both human and mouse antibodies have different abilities to fix complement and to bind to Fc receptors.[ citation needed ]
The measurement of immunoglobulin G can be a diagnostic tool for certain conditions, such as autoimmune hepatitis, if indicated by certain symptoms. [18] Clinically, measured IgG antibody levels are generally considered to be indicative of an individual's immune status to particular pathogens. A common example of this practice are titers drawn to demonstrate serologic immunity to measles, mumps, and rubella (MMR), hepatitis B virus, and varicella (chickenpox), among others. [19]
Testing of IgG is not indicated for diagnosis of allergy, and there is no evidence that it has any relationship to food intolerances. [20] [21] [22]
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.
CD32, also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in monomeric form, but high affinity for IgG immune complexes. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include phagocytosis, cytokine stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of autoimmunity, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.
A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Friedrich von Recklinghausen and later rediscovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumors.
Hypersensitivity is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes immune diseases including allergies and autoimmunity. It is caused by many types of particles and substances from the external environment or from within the body that are recognized by the immune cells as antigens. The immune reactions are usually referred to as an over-reaction of the immune system and they are often damaging and uncomfortable.
Immunoglobulin A is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other types of antibody combined. In absolute terms, between three and five grams are secreted into the intestinal lumen each day. This represents up to 15% of total immunoglobulins produced throughout the body.
Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.
Immunoglobulin M (IgM) is the largest of several isotypes of antibodies that are produced by vertebrates. IgM is the first antibody to appear in the response to initial exposure to an antigen; causing it to also be called an acute phase antibody. In humans and other mammals that have been studied, plasmablasts in the spleen are the main source of specific IgM production.
Type I hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Type I is distinct from type II, type III and type IV hypersensitivities. The relevance of the Gell and Coombs classification of allergic reactions has been questioned in the modern-day understanding of allergy, and it has limited utility in clinical practice.
In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades. Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. Memory B cells have B cell receptors (BCRs) on their cell membrane, identical to the one on their parent cell, that allow them to recognize antigen and mount a specific antibody response.
Antibody opsonization is a process by which a pathogen is marked for phagocytosis through coating of a target cell with antibodies. Immunoglobulins participate in molecular tagging of pathogens which display antigens recognised by their specific paratope. The binding of antibodies enhances pathogen identification and recruitment of immune effector cells, ultimately accelerating microbial clearance through phagocytic destruction or antibody-dependent cellular cytotoxicity.
In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.
The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-affinity receptor for the Fc region of immunoglobulin E (IgE), an antibody isotype involved in allergy disorders and parasite immunity. FcεRI is a tetrameric receptor complex that binds Fc portion of the ε heavy chain of IgE. It consists of one alpha, one beta, and two gamma chains connected by two disulfide bridges on mast cells and basophils. It lacks the beta subunit on other cells. It is constitutively expressed on mast cells and basophils and is inducible in eosinophils.
Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the isotype IgM to the isotype IgG. During this process, the constant-region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same. Since the variable region does not change, class switching does not affect antigen specificity. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.
The word allotype comes from two Greek roots, allo meaning 'other or differing from the norm' and typos meaning 'mark'. In immunology, allotype is an immunoglobulin variation that can be found among antibody classes and is manifested by heterogeneity of immunoglobulins present in a single vertebrate species. The structure of immunoglobulin polypeptide chain is dictated and controlled by number of genes encoded in the germ line. However, these genes, as it was discovered by serologic and chemical methods, could be highly polymorphic. This polymorphism is subsequently projected to the overall amino acid structure of antibody chains. Polymorphic epitopes can be present on immunoglobulin constant regions on both heavy and light chains, differing between individuals or ethnic groups and in some cases may pose as immunogenic determinants. Exposure of individuals to a non-self allotype might elicit an anti- allotype response and became cause of problems for example in a patient after transfusion of blood or in a pregnant woman. However, it is important to mention that not all variations in immunoglobulin amino acid sequence pose as a determinant responsible for immune response. Some of these allotypic determinants may be present at places that are not well exposed and therefore can be hardly serologically discriminated. In other cases, variation in one isotype can be compensated by the presence of this determinant on another antibody isotype in one individual. This means that divergent allotype of heavy chain of IgG antibody may be balanced by presence of this allotype on heavy chain of for example IgA antibody and therefore is called isoallotypic variant. Especially large number of polymorphisms were discovered in IgG antibody subclasses. Which were practically used in forensic medicine and in paternity testing, before replaced by modern day DNA fingerprinting.
In immunology, antibodies are classified into several types called isotypes or classes. The variable (V) regions near the tip of the antibody can differ from molecule to molecule in countless ways, allowing it to specifically target an antigen . In contrast, the constant (C) regions only occur in a few variants, which define the antibody's class. Antibodies of different classes activate distinct effector mechanisms in response to an antigen . They appear at different stages of an immune response, differ in structural features, and in their location around the body.
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-2-like cytokine, alarmin, and growth factor involved in numerous physiological and pathological processes, primarily those of the immune system. It shares a common ancestor with IL-7.
Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.
The following outline is provided as an overview of and topical guide to immunology:
Lirentelimab is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis. Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.
Long-lived plasma cells (LLPCs) are a distinct subset of plasma cells that play a crucial role in maintaining humoral memory and long-term immunity. They continuously produce and secrete high-affinity antibodies into the bloodstream, conversely to memory B cells, which are quiescent and respond quickly to antigens upon recall.