Antibody

General structure

The antibodies are Glycoprotéine S of the Superfamille of the formed immunoglobulins of 4 polypeptide chains (150.000 uma): 2 heavy chains ( H for heavy of 50.000uma each one, purple on figure 1) and 2 light chains ( L for light of 25.000 uma each one, in green) which are connected between them by a variable number of bridges disulfides (in red) ensuring a flexibility of the molecule. These chains form a structure in Y and consist of fields immunoglobulin S of 110 amino-acid approximately. Each light chain consists of a constant field and a variable field; the heavy chains are made up of a variable fragment and 3 or 4 constant fragments according to the isotypic one. For a given antibody, the two heavy chains are identical, the same for the two light chains.

Figure 1: Diagram of a anticorps.

Constant fields

The constant fields are characterized by a sequence in amino-acids very near from one antibody to another, characteristic of the species and the isotypic one. Each light chain has of it a specimen noted C_L. The heavy chains comprise, according to isotypic, the three or four constant fields C_H1, C_H2, C_H3 and C_H4.
the constant fields are not implied in the recognition of the antigen, but intervene in the activation of the Système of the complement. The immunizing cells having the receivers with the constant fragments (RFC) are able to bind the antibodies.

Variable fields

An antibody has four variable fields located at the ends of the two “arms”. Association between a variable field carried by a heavy chain (V_H) and the adjacent variable field carried by a light chain (V_L) constitute the site of recognition (or Paratope) of the antigen. Thus, an immunoglobulin molecule has two sites of connection to the antigen, one at the end of each arm. These two sites are identical, from where the possibility of binding two antigen molecules by antibody.

Isotypie, Allotypie, Idiotypie

Isotypie

The antibodies (historically named Ig because they were used for the definition of the term Immunoglobuline) are subdivided in isotypic classes or , according to the structure of the constant fields of the heavy chains: the chains γ, α, μ, ε and δ correspond respectively to the immunoglobulins IgG, IgA, IgM, IgE and IgD (see Tableau 1). There exist also immunoglobulin subclasses, reflecting finer differences between heavy chains. The man thus has four subclasses of IgG and 2 subclasses of IgA. There exist also the isotypic ones of light chains, those being able to be κ (kappa) or λ (lambda).

Tableau 1: Properties of different isotypic from immunoglobulines.

Allotypie

It is into 1956 that Grubb and Laurell discovered the Gm system, system of group of the IgG immunoglobulins. This system highlights various the allotypes heavy chains. It also makes it possible to differentiate the molecules from the four subclasses, IgG1, IgG2, IgG3, IgG4.

C. Ropartz and coll in 1961 discovered system km (at the origin called Inv), carried by the light chain Kappa, this allotype is thus present on all the immunoglobulin class.

Finally the ISf system located on the heavy chain γ1 of IgG1, the expression of this specificity increasing with the age, of 25% of the subjects before 20 years with 60% beyond 70 years, at the Caucasians.

The allotypes defined by the system Am are located on IgA, and more precisely on the chains α2. There exist two isotypic α1 and α2 of chains α, characterizing the Am1 subclasses and Am2 of IgA.

Idiotypie

The idiotype is a épitope specific to a molecule resulting from only one clone. This épitope forms part or is very close to the site of recognition of the antigen, and is thus located on the variable part, Fab (fragment antigen binding), of immunoglobulin. In other words, the paratope or its area close to an immunoglobulin can be recognized like a épitope by certain lymphocytes. From where idiotypic concept of network.

Role of the antibodies

Figure 2: Bacterial toxins au
voisinage of a cell (high),
neutralization by antibodies (low).

During the immunizing response, the antibodies have three principal functions: to bind to the antigen, to activate the system of the complement and to recruit cells immunocompétentes.

Connection with the antigen

The antibodies have the capacity to recognize and to be fixed in a specific way on an antigen. This specificity is conferred by the presence of extremely variable fields at the ends of the antibodies. The recognition between antigen and antibody for example is made profitable in the fight against bacterial toxins. These toxins act while being fixed on receivers present at the surface of the cells of the organization, which causes important disordered states of the cellular activity. While being fixed on these toxins, the antibodies antitoxin neutralize them and prevent the connections with the cellular receivers (see figure 2).

Same manner, many viruses and bacteria exert their pathogenicity only after fixing with the cells of the organization. The bacteria use adhésines which are molecules of adhesion to the cellular membranes and the viruses have proteins of fixing on their external envelope. The anti-adhésines antibodies and anti-proteins of the viral capsid block the action of these disease-causing agents while binding on the molecules of fixing.

Activation of the complement

The antibodies also protect the organization by starting the cascade from the complement. It is about a whole of proteins of the plasma whose activation (by the traditional way in the case of antibody) makes it possible to destroy bacteria by perforation and to facilitate the Phagocytose, the elimination of the complex immunes and the release of chimiotactic molecules . What brings us to the hémolyse red globule.

Activation of cells immunocompétentes

After having recognized an antigen thanks to its variable part, an antibody can bind to cells of the immune system by its constant part. These interactions are of a great importance in the course of the immunizing response. Thus, the antibodies fixed on a bacterium can bind to the Macrophage S and start a phagocytosis. The Lymphocytes NK (Natural Killer) can exert to them Cytotoxicité and lyse opsonized bacteria by antibodies.

Synthesis of the antibodies

General information

The antibodies are coded by genes undergoing a Recombinaison V (D) J in the lymphocytes B. This recombination is the source of their diversity.

Commutation of class

During maturation of a lymphocyte B, and according to the stimuli which accompanied this maturation, the clones of cells B recognizing the épitope undergo a commutation of class. The immature cells B, which basic express only of IgM and IgD, can evolve/move not to produce more but one isotypic (IgM, IgE, IgA or IgG), by operating a recombination of gene coding fragment FC of the heavy chains, but by keeping intact the variable fragment.

Monoclonal and polyclonaux antibody

Figure 3: Monoclonal antibodies,
liaison with a épitope spécifique.

Figure 4: Polyclonaux antibody,
liaison with épitopes différents.

An disease-causing agent (Bactérie, Virus, etc) is recognized by the immune system via Antigène S. an antigen generally has several épitope S different which is as many sites of connection to the antibodies. One can classify a population of antibody according to his capacity to recognize only one or several épitopes. One speaks then respectively about monoclonal and polyclonaux antibody.

Monoclonal antibodies

See also: monoclonal Antibodies

The monoclonal antibodies are antibodies recognizing one type of épitope on a given antigen (see figure 3). They by definition all identical and are produced by only one clone of Plasmocyte.

The monoclonal antibodies are very largely used in Biologie and Médecine, at the same time like tools of diagnosis and with therapeutic aims. The monoclonal antibodies used as drugs have a whole a DCI ending in " mab" , acronym of " monoclonal antibody" such as for example the Rituximab. They for example are used in the tests of pregnancy sold in the trade. They are used in many fields of the Recherche in Biologie by many techniques, such as the Cytométrie in flow or the Western blot S for example. They are used also more and more in the tests in laboratory of immuno-hematology to raise the positive reactions.

The production of monoclonal antibodies in vitro was made difficult a long time because of the weak lifespan of the secreting cells of antibody, the plasmocytes. The antibodies were then obtained in vivo by injecting in the animal a given antigen and by collecting the antibodies in blood. This method was very expensive, gave antibodies in small quantities and polluted by many impurities. An major advance was made at the end of the Années 1970 by César Milstein and Georges Köhler with the technique of the Hybridome S. the antigen is injected in the animal, and of the cells of Rate are taken at the end of a few weeks. Among these cells plasmocytes secreting of the antibodies directed specifically against the selected antigen are. The plasmocytes are then amalgamated in vitro with myélomes, which are tumoral cells having the property to multiply indefinitely. The hybrid cells thus obtained are called hybridomes and, after selection and multiplication in a suitable Culture medium, produce monoclonal, very pure antibodies and in significant amounts.

Thanks to the techniques of genetic Engineering, it is from now on possible to produce in practice clinical antibodies monoclonal usable human. But the majority of the antibodies being produced in cells of Rodent S (Mouse, Rat, Hamster, Rabbit more rarely Chicken, Mule), they start an immune reaction during their injection to a patient. This inactive immunity gradually the beneficial action of the antibody. To avoid that, one produces chimerical antibodies " humanisés" , modified by genetic engineering to replace to the maximum constant fragments FC of the species of origin by human fragments.

Polyclonaux antibody

The polyclonaux antibody are a mixture of different antibodies recognizing épitope S on a given antigen, each idiotype being secreted by a clone of different plasmocyte. During the immunizing response, an organization synthesizes antibodies directed against several épitope S of an antigen: the answer is known as polyclonale. In vivo , the answer is always polyclonale, except exceptional cases (Vaccination for example). This example is in fact an example of antibody polyclonal monospecific which is in fact an antibody which recognizes different épitope S from the same antigen whereas an antibody polyclonal recognizes the épitope S of various antigens.

Appendices

External bonds

Site of the medical students of Grenoble
Microbiology and on-line Immunology (in English)
Site SVT of the Academy of Lyon

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