![]() Once the TFR is recycled and returns to the cell membrane, apo-TF is released to the extracellular matrix. Iron-free TF (apo-TF) has an affinity to TFR at this pH. Acidic pH of the endosomic lumen causes a conformational change in TF, which causes the release of iron. Circulating TF binds to TFR when it is loaded with iron and internalized by receptor mediated endocytosis. Iron bound TF (holo-TF) has high affinity to TFR at physiological pH. Transferrin (TF) is a vital protein facilitating iron uptake by the cells. In order to induce the immunogenicity of haptens, whether they are needed for antibody development or vaccine studies, they are chemically conjugated to immunogenic proteins, and act as a part of that protein. Only peptides can be presented via MHC molecules therefore, proteins are the strongest immunogens, and haptens cannot elicit immune response. After internalization, the antigen is processed by digestion into fragments, and combined with MHC molecules to be presented on the cell surface. The internalization is either by phagocytosis or receptor mediated endocytosis. ![]() When an antigen enters the body, it is internalized by a group of cells called APCs, which include dendritic cells, macrophages, and B cells themselves. ![]() However, the encounter of T cells with the antigen should be through specialized molecules called “major histocompatibility complexes” (MHCs) on the surface of antigen presenting cells (APC). The B cell needs the assistance of another group of immune cells called T cells for stimulation, and T cells also need to be activated via antigen encounter. The antigen encounter is necessary but not enough for antibody production. A mature B cell lives for 3–4 days and dies unless it encounters the specific antigen with structural compatibility to its BCR. Due to extensive genetic variability, which is beyond the scope of this paper, there may be more than 10 11 different receptors with different antigen specificities. These receptors are immunoglobulins embedded the cell membrane which serve as B-cell receptors (BCR). In the mammalian body, there is a repertoire of mature B cells, each of which express a different cell surface receptor. B cells of the immune system are specialized cells for the production of antibodies. To be able to induce such immunogenicity in these non-immunogenic antigens, we first need to understand the mechanism of antibody production.Īntibodies are produced as the defense molecules of the body through humoral immune response. But we sometimes need a humoral immune response against hapten molecules, because we need antibodies to use in immunodiagnostic systems. Haptens are not immunogenic because even though they may pose a threat to the organism, like in the case of mycotoxins, they can be detoxified by chemical modification with liver enzymes, and there is no need to start the energy consuming humoral immune response. There are non-immunogenic antigens, like some bacterial toxins which non-specifically induce the immune system to exhaustion which are called “superantigens”, or some molecules which are too small to be immunogenic are called “haptens”. All immunogens are at the same time antigens, but the reverse is not true. An immunogen, on the other hand, is a molecule which not only binds to these molecules, but is also capable of triggering the cell-mediated immune response or humoral immune response and the production of antibodies. Monoclonal antibodies were successfully developed with mice immunized with either of the conjugates.Īn antigen is any molecule that can bind to the surface receptors of immune system cells and antibodies. Transferrin conjugates induced aflatoxin-specific immune responses in the second immunization, while ovalbumin conjugates reached similar antibody titers after 5 injections. We conjugated aflatoxin, a potent carcinogenic food contaminant, to transferrin and evaluated its potential to stimulate antibody production with respect to ovalbumin conjugates. Here, we induced an endocytic receptor, transferrin receptor, by selecting its ligand as a carrier protein to enhance antibody production. However, the carrier is usually considered merely as a bulk mass, and its biological activity is ignored. Immunogenic forms of haptens are usually prepared by conjugating them to a protein carrier which serves as an immune stimulator. However, antibody development for these molecules is a challenge, because they are haptens and cannot induce a humoral immune response in experimental animals. Immunoanalytical methods are frequently employed in the detection of hazardous small molecular weight compounds.
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