Antibody synthesis Immune system

Antibodies are immune system-related proteins called immunoglobulins. An important component of the immune system, antibodies are found in the blood of all vertebrates. The synthesis, or manufacture, of antibodies is initiated when a foreign substance, referred to as an antigen, enters the body. Lymphocyte cells respond to the foreign substance by making an antibody with a molecular arrangement that fits the shape of molecules on the siuface of the substance so that the antibody combines with it. Common antigens are the protein components of bacteria and viruses. 

Cytokines. Figure 1 Inhibition of cytokine synthesis during activation of the specific immune system. The monoclonal antibodies Muromonab and Basiliximab are specific for the CD3 complex of the T-cell receptor, and for the IL-2 receptor on lymphocytes, respectively. Cyclosporin and Tacrolimus inhibit activation of cytoplasmic NF-AT, a transcription factor essential for activation of the IL-2 gene ( NFAT Family of Transcription Factors). Sirolimus interferes with mTOR signaling and inhibits IL-2 dependent proliferation. Red pharmaka, blue target proteins. 

After this initial phase of infection subsides, the free viral load in the blood declines, often to almost undetectable levels. This latent phase may last for anything up to 10 years or more. During this phase, however, there does seem to be continuous synthesis and destruction of viral particles. This is accompanied by a high turnover rate of (CD4+) T-helper lymphocytes. The levels of these T-lymphocytes decline with time, as does antibody levels specific for viral proteins. The circulating viral load often increases as a result, and the depletion of T-helper cells compromises general immune function. As the immune system fails, classical symptoms of AIDS-related complex (ARC) and, finally, full-blown AIDS begin to develop. 

The anticonvulsant phenytoin, and to a lesser degree carbamazepine, can inhibit the synthesis of antibodies, and in some cases these drugs can result in lymphoproliferation [77-79]. These effects on the immune system could be viewed as a type of autoimmunity. The relationship between such effects and autoimmunity are still not clear, although the more recent observations that cytokines and anti-cytokines can cause autoimmunity support the existence of such a relationship. The previous edition of this book contained an extensive discussion of the possible relationship between immunosuppression and autoimmunity [80], Phenytoin and carbamazepine can also cause a lupus-like syndrome although the incidence is lower than with many other drugs. 

An important application of fluorescence is in immunoassays, which employ antibodies to detect analyte. An antibody is a protein produced by the immune system of an animal in response to a foreign molecule called an antigen. The antibody recognizes the antigen that stimulated synthesis of the antibody. The formation constant for the antibody-antigen complex is very large, whereas the binding of the antibody to other molecules is weak. 

Several effects of forskolin on B-lymphocytes, the cells of the immune system responsible for the production of immunoglobulins, have further been reported. This diterpene was found to inhibit cellular proliferation of B cells stimulated either by antibodies to surface immunoglobulins (anti-mu), and an antibody to CD20 antigen or 12-O-tetradecanoyl phorbol 13-acetate [219]. There was also a clear inhibition of G1 entry and DNA synthesis, and forskolin maintained its inhibitory effect even when added later after anti-mu stimulation. Additionally, no differences were found in the inhibitory effect of forskolin on neoplastic B cells, as compared to the responses of normal cells. Growth inhibition associated with an accumulation of cells in G1 was later found when cells of the B-lymphoid precursor cell line Reh were incubated with forskolin [220]. In that study, a delay of cells in G2/M prior to G1 arrest was observed, suggesting that important restriction points located in the G1 and G2 phases of the cell cycle may be controlled by forskolin (due to cAMP levels elevation). In a subsequent study [221], it was found that the arrest of Reh cells was accompanied by rapid dephosphorylation of retinoblastoma protein, which was suggested to be a prerequisite for the forskolin mediated arrest of these cells in Gl. 

Related topics The immune system (Dl) Antibody synthesis (D4)... 

Since natural enzymes are unable to accept all of the unnatural substrates that they are called upon to accept for organic synthesis applications, alternative biocatalysts with expanded substrate specificity are needed. One approach toward the generation of new biocatalysts is to exploit the molecular diversity of the immune system by recruiting catalytic antibodies as protein catalysts. 

In this chimeric peptide construct the aim was to combine the carrier function and immunstimulatory activity of tuftsin derivatives with an epitope derived from HSV gD to achieve an increased antibody response. Tuftsin is a well-known natural tetrapeptide (TKPR) that has a pronounced effect on the immune system (28,29). Polymerized tuftsin (polytuftsin) is also considered as a carrier molecule that increased antibody levels against attached epitopes in mice (30,31). New, sequential oligopeptides based on repeated tuftsin derivatives (H-[Thr-Lys-Pro-Lys-Gly]n-NH2, where n = 2,4,6,8) were developed in our laboratory to eliminate the drawbacks of tuftsin derivatives produced by polymerization. These new, nontoxic, nonimmunogenic compounds have immunostimulatory activity and a minor chemoattractant effect on monocytes (32). An oligotuftsin derivative was used in this study for the synthesis of a peptide chimera containing an HSV peptide epitope. 

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