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The Inducible System: Antigens
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Any molecule that will induce an immune response and interact specifically with the products of the induced immune response is an antigen, Immunogen is another term preferred by some for molecules that will induce such a response. Classically, antigens have been considered to consist of a hapten, which cannot induce an immune response by itself, and a carrier protein which will induce a response. An antigenic determinant, or epitope, is the site on an antigen to which the antibody binds. The three-dimensional shape, amino acid sequence, and ionic charge of the antigen are all crucial to antibody binding. T cell receptors bind to protein fragments presented on the surface of MHC proteins. Therefore, the TCR recognizes two molecules at once: the MHC protein and the presented antigen-fragment.
Pharmacology of Local Anesthetics
Published in Pamela E. Macintyre, Stephan A. Schug, Acute Pain Management, 2021
Pamela E. Macintyre, Stephan A. Schug
Ester local anesthetic drugs are metabolized in plasma (and to a lesser extent the liver) by pseudocholinesterases; thus, their half-lives in the circulation are shorter than amide local anesthetic drugs (Becker & Reed, 2012; Mather & Tucker, 2009). These drugs are thought to have a greater potential to cause allergic reactions as they are metabolized to para-amino benzoic acid, which acts as a hapten; however this has not been proved (Lirk et al, 2018). They are also less stable in solution than amide local anesthetics. For these reasons, they are no longer widely used and are more of historical interest. In particular, they play no role in the treatment of acute pain and will therefore only be discussed briefly.
Monographs of fragrance chemicals and extracts that have caused contact allergy / allergic contact dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
In groups of patients allergic to cinnamyl alcohol, reduced rates of both ‘current’ and ‘past’ atopic dermatitis have been found, which was not the case with fragrances with only cutaneous exposure. It has been suggested that such atopic individuals have heightened oral tolerance to dietary haptens (118).
Evaluation of pathophysiological relationships between renin-angiotensin and ACE-ACE2 systems in cardiovascular disorders: from theory to routine clinical practice in patients with heart failure
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
Alberto Aimo, Giuseppe Vergaro, Claudio Passino, Aldo Clerico
However, more than 20 years ago, Grassi et al. [125] suggested two different approaches for developing sensitive and specific immunometric assays for haptens, including small peptides such as Angio-II. The first approach for small peptides (8–11 amino acids) is based on the selection of two sets of antibodies specifically directed against the C- and N-terminal moieties of the peptide. The second approach is based on a solid-phase-immobilized epitope immunoassay in which a single monoclonal antibody uses the same epitope for capture and tracer binding, and the hapten analyte (i.e. the small peptide) is covalently cross-liked to a solid-phase [125]. Unfortunately, at this time, all the commercially available immunometric assays for Angio-II are approved for research only (Table 3) [86,92,114–123]. Furthermore, these assay methods are laborious and time consuming due to the need for manual preparation of reagents, long incubation times, and non-automatic instrumentation for fluorescence/luminescence detection [86,92,114–123], limiting their application in a clinical setting.
Novel chimeric monoclonal antibodies that block fentanyl effects and alter fentanyl biodistribution in mice
Published in mAbs, 2021
Bhupal Ban, Rodell C. Barrientos, Therese Oertel, Essie Komla, Connor Whalen, Megan Sopko, Yingjian You, Partha Banerjee, Agnieszka Sulima, Arthur E. Jacobson, Kenner C. Rice, Gary R. Matyas, Vidadi Yusibov
Current research efforts are focused on developing alternatives or complementary modalities to the four approved products. An alternative approach to treat substance use disorders is use of vaccines or biologics that target specific drugs of abuse (DoA). Although the proof-of-concept for vaccines against DoA was demonstrated over 40 years ago,12,13 it has taken decades for the use of vaccines to treat SUDs to gain momentum. In the early 1970s, seminal efforts were devoted to hapten design that mimicked morphine, methamphetamine, and nicotine. These haptens, primarily, were used to generate antibodies for the detection of DoA. This area of research waned by the 1980s, but, over the past 15–20 years, interest in drug-specific antibodies resurfaced. As such, continued efforts to improve hapten design have led to vaccine candidates that can induce effective antibodies.14,15 When the DoA enters the bloodstream, these antibodies bind the drug and impede it from crossing the blood–brain barrier, thereby preventing it from interacting with its molecular target (e.g., the µ-opioid receptor) in the central nervous system (CNS).
Vaccine development against methamphetamine drug addiction
Published in Expert Review of Vaccines, 2020
Md Kamal Hossain, Majid Hassanzadeganroudsari, Kulmira Nurgali, Vasso Apostolopoulos
The conjugate vaccines development strategies through hapten design have been studied most extensively for all the drugs of abuse including METH [8,9]. METH is a small molecule and the body’s immune system cannot recognize it. Therefore, METH or METH with a linker (hapten) needs to be tagged with a known immunogenic carrier to be recognized by the immune system and its effective processing (Figure 2) [8,29]. This strategy has been shown to be effective for both nicotine and cocaine vaccines and the strategy is viable for the application of developing a vaccine against METH [8]. In order to prevent METH from entering the central nervous system (CNS), a high concentration of anti-METH antibodies is required. The selectivity and affinity of the anti-METH antibody largely depend on an effective METH hapten molecule. This is a significant challenge as METH is a small molecule with limited chemical epitope [8,20]. Inclusion of a linker at the appropriate position of the ‘hapten’ (METH) is crucial for the generation of high antibody titers and antibody specificity [30]. Hence, the proper design of hapten is important for immune recognition due to its role in the presentation of target antigen to the antigen presenting cell. A series of METH haptens have been investigated (Table 1) by various research groups in the last few decades in regards to their efforts to develop a METH vaccine (hapten-carrier approach).