What Is the Basic Antibody Structure?

Antibodies refer to proteins with protective effects produced by the body due to the stimulation of antigens. It (immunoglobulin is not just an antibody) is a large Y-shaped protein secreted by plasma cells (effector B cells) and used by the immune system to identify and neutralize foreign substances such as bacteria and viruses. The surface of cell membranes of vertebrate blood and other B cells. Antibodies recognize a unique feature of a particular foreign object, which is called an antigen. ^[1]

Antibodies are a class of immunoglobulins that specifically bind to an antigen. Antibodies are divided into lectin, sedimentin, antitoxin, lysin, opsonin, neutralizing antibody, complement-binding antibody and so on according to their reaction forms. According to the source of antibody production, it is divided into normal antibodies (natural antibodies), such as anti-A and anti-B antibodies in the blood group ABO type, and immune antibodies such as anti-microbial antibodies. Divided into heterogeneous antibodies, heterotropic antibodies, alloantibodies and autoantibodies according to the source of the reactive antigen. According to the agglutination state of antigen reaction, it is divided into complete antibody IgM and incomplete antibody IgG. Antibodies are widely used in medical practice. For example, it has certain effects in the prevention, diagnosis and treatment of diseases. Clinically, gamma globulin is used to prevent viral hepatitis, measles, rubella and the like, and anti-Rh immunoglobulin is used internationally to prevent hemolysis caused by Rh blood group incompatibility. Diagnostics such as rheumatoid factor for rheumatoid arthritis, antinuclear antibodies (ANA), anti-DNA antibodies for systemic lupus erythematosus, antisperm antibodies for the diagnosis of primary infertility, etc. Antipoison treatment for poisoning and treatment of immunodeficiency diseases. ^[2-3]

In the late 19th century, V on Behring and his colleague Kitasato found that immunizing animals with diphtheria or tetanus toxin can produce a substance that neutralizes toxins, called antitoxin, and then introduced the term "antibody" Refers to antitoxins. Antibodies (antibody, Ab) are glycoproteins produced by B cells undergoing antigen stimulation to proliferate and differentiate into plasma cells. They are mainly present in body fluids, such as serum, and are important effector molecules for mediator fluid immunity. Exert immune function. In 1937, Tiselius and Kabat used electrophoresis to separate serum proteins into albumin, 1, 2, , and gamma globulin, and found that antibodies mainly exist in the gamma region, so antibodies are also called gamma globulin. Subsequently, after discussions between the World Health Organization and the Immune Society in 1968 and 1972, the globulins with antibody activity or chemical structure similar to antibodies were collectively named immunoglobulin (Ig). Ig can be divided into secreted Ig (Secreted Ig, SIg) and membrane type Ig (Membrane Ig, mlg). Slg mainly exists in blood and interstitial fluid, and performs various functions of antibodies; mlg mainly constitutes the antigen receptor on the surface of B cell membranes ^[4]

First, the basic structure of antibodies

X-ray crystal structure analysis showed that Ig was composed of four polypeptide chains, and the number of interchain disulfide bonds between the peptide chains varied. Ig can form a "Y" -shaped structure, called an Ig monomer, and is the basic unit of antibodies. ^[4]

The function of an antibody is closely related to its structure. The difference in the amino acid composition and sequence of the V region and c region of the same antibody determines the functional differences. The V and C regions of different antibodies have certain rules in structural changes, which in turn makes them functionally similar. The composition and structure of the V and C regions determine the biological function of the antibody. ^[4]

First, IgG

IgG is synthesized 3 months after birth, and it is close to the adult level at the age of 3 to 5. IgG is the highest level of antibody in serum and body fluids, accounting for 75% to 80% of total serum Ig. There are 4 subclasses of human lgG, which are sorted according to their concentration in the serum, respectively IgG1, IgG2, IgG3, and IgG4. IgG has a half-life of 20 to 23 days. It is the main antibody produced by the re-immune response. It has high affinity, is widely distributed in the body, has important immune effects, and is the "main force" of the body against infection. IgG1, IgG2, and IgG3 can cross the placental barrier and play an important role in anti-infection immunity in newborns. IgG1, lgG2, and IgG3 can activate complement through classical pathways, and can bind to Fc receptors on the surface of macrophages and NK cells to exert opsonization and ADCC effects; human IgGl, IgG2, and IgG4 can interact with staphylococcal proteins through their Fc segments A (SPA) binding, whereby antibodies can be purified and used for immunodiagnosis. Certain autoantibodies such as anti-thyroglobulin antibodies, antinuclear antibodies, and antibodies that cause type II and III hypersensitivity reactions also belong to IgG ^[4]

The unique biological activity of antibodies makes them play an important role in disease diagnosis, immune prevention and basic research. As early as the late 19th century, people began to immunize animals with specific antigens to prepare corresponding antisera. In 1975, Kohler and Milstein established the monoclonal antibody (monoclonai antibody, mAb) technology, which made it possible to prepare highly specific and homogeneous antibodies on a large scale. However, the emergence of human anti-mouseantibody (HAMA) from mouse-derived mAbs after repeated immunizations in humans has largely limited the clinical use of mAbs. In recent years, with the development of molecular biology, people have been able to prepare human-mouse chimeric antibodies, humanized antibodies, or humanized antibodies through antibody technology. ^[4]

There are many kinds of antibodies in human serum. The types of antibodies produced by B lymphocytes are above 10 ⁸ and can specifically bind to many different antigens. There are two main reasons for antibody diversity:

1. There are many types of antigens in the environment of exogenous factors, and each macromolecular antigen has multiple antigenic epitopes. Each epitope can choose to activate a B cell clone in the body to produce a specific antibody.

2. Endogenous factors Another reason for antibody diversity is determined by the structural and functional characteristics of genes. The genes encoding human Ig heavy chain and kappa and lambda light chains are located on chromosomes 14, 2 and 22, respectively. The genes encoding the Ig heavy chain include V, D, J encoding the variable region and the C gene encoding the constant region; the genes encoding the Ig light chain include V, J encoding the variable region, and the C gene encoding the constant region. Each gene fragment exists in multiple copies. The number of VH, DH, and JH gene fragments encoding the heavy chain V region is 50, 23, and 6, respectively; the number of Vx and JK gene fragments encoding the K light chain V region There are 60 and 5, respectively, and the number of VX and J genes into the light chain V region is 30 and 7, respectively. These genes exist in separate forms at the germline stage. During the differentiation and development of B cells, these gene fragments are rearranged and combined, resulting in a large number of BCRs that can recognize specific antigens. Each B-cell clone with a specific BCR recognizes the corresponding antigen and produces a specific antibody. Ig gene recombination is the main reason why B cells synthesize countless specific antibodies. ^[6]

All higher animals (including humans) that can produce antibodies have the same law of antibody production when injected with thymus-dependent antigen (TD antigen) for immunization, that is, there is a primary immune response and a secondary immune response response). The primary immune response refers to the process in which the body's first contact with an antigen substance causes specific antibody production. It is characterized by a long incubation period (more than one week), low antibody titer (titer), and short maintenance time. The antibodies produced are mainly IgM; the re-immune response refers to the body's subsequent production after it contacts the same antigen again Antibody response process. It is characterized by the short incubation period of antibody production, high antibody titer, and long maintenance time. The antibodies produced are mainly IgG.

Because humoral immunity caused by non-thymus-dependent antigens (TI antigens) does not produce memory cells, there is only a primary immune response and no further immune response. ^[7]