The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Each B cell expresses multiple copies of the same antigen-specific receptor on its cell surface. These structures are commonly called B cell Receptors (BCR). The receptor has the basic immunoglobulin structure, consisting of two L chains paired with either two μ chains (IgM) or two δ chains (IgD) (Figure 7.8). Both types of BCR on a given cell have the same H and L variable (V) region and thus the same antigen-specificity. Since the BCR is composed of immunoglobulin, it is also often referred to as surface lg (slg). The receptor has a transmembrane domain that anchors it to the cell surface. Ln addition, there are proteins associated with the BCR, called iga and igβ, that are involved in transmembrane cell signaling. The binding of the BCR with an epitope along with other costimulatory molecules signals the B cell to begin clonal expansion. Some of the daughter cells resulting from this expansion develop into plasma cells. Antibodies secreted by these plasma cells have the same specificity as the BCR on the original B cell.
Dopamine Receptors, Signaling Pathways, and Drugs
Nira Ben-Jonathan in Dopamine, 2020
Receptor desensitization is defined as a time-dependent diminished responsiveness to a bound agonist that affects the dynamics, plasticity, and the overall activity of a given receptor. Desensitization protects against receptor overstimulation and enables the integration of a biological signal through feedback from second messengers [37]. Therapeutically, however, desensitization is viewed as a considerable impediment because it ultimately limits the efficacy of some drugs. Two types of desensitization modes have been recognized: homologous and heterologous [7]. Homologous desensitization refers to loss of response to an agonist that acts upon a specific receptor subtype, whereas heterologous desensitization refers to diminished responsiveness to a ligand resulting from input by signaling component(s) downstream of the receptor [38].
Receptor-Ligand Interactions that are Disaproportionate With Their Physiological Effects
John C. Matthews in Fundamentals of Receptor, Enzyme, and Transport Kinetics, 2017
RLS is the stimulated receptor-ligand complex and RLdes is the desensitized receptor-ligand complex. The nicotinic acetyl choline receptor of the mammalian neuromuscular junction is an example of a receptor system that automatically desensitizes shortly after the stimulated receptor-ligand complex has formed. Desensitization functions physiologically to provide an automatic off switch for this receptor-mediated signal transduction system. Often, desensitization is accompanied by a decrease in the affinity of the receptor for its agonists, but this is not always the case. With desensitization, BL is not proportional to SL. If desensitization changes the affinity for L it could cause Eadie-Hofstee or Rosenthal-Scatchard plots to be nonlinear. This is shown in Figure 29. The concave curvature of Figure 29 is the result of a summation of binding to two sets of sites having different affinities and different BLmax values. This is indicated by the dashed lines. This behavior is described by Equation 85:
Emerging drugs in the treatment of chronic cough
Published in Expert Opinion on Emerging Drugs, 2023
Danica Brister, Mustafaa Wahab, Moaaz Rashad, Nermin Diab, Martin Kolb, Imran Satia
The involuntary cough reflex is designed to protect against aspiration of food, foreign bodies and prevent the inhalation of noxious gases. It can be triggered by stimulation of peripheral receptors of vagal nerve fibers innervating the larynx, upper and lower airways. There are at least two known subtypes of vagal nerve afferents involved in the cough reflex response; myelinated A fibers which originate in the nodose ganglion, and the slower, unmyelinated C-fibers of the jugular ganglion (Figure 1) [50,51]. A fibers are predominantly mechanosensitive, whilst C-fibers are activated by chemical and temperature triggers and will respond to flavors and fragrances such as capsaicin, garlic, cinnamaldehyde, and methanol [51–53]. Multiple receptor subtypes have been identified on these afferent fibers, including ligand gated ion channels (LGIC), and G protein coupled receptors. LGIC include transient receptor protein (TRP) vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and TRP melastin 8 (TRPM8) can be found on both alpha-delta and c-fibers [50,52]. Purinergic receptors, such as P2×3, are activated by extracellular ATP release in response to cellular injury and within the upper airway are expressed on C-fibers of the jugular ganglion [10]. Patients with RCC/UCC demonstrate a heightened response to capsaicin inhalation compared to healthy controls, which may be mediated by more peripheral receptors, the or the sensitization of peripheral nerves [10].
Second messengers and their importance for novel drug treatments of patients with bipolar disorder
Published in International Review of Psychiatry, 2022
Gabriele Sani, Georgios D. Kotzalidis, Federica Fiaschè, Giovanni Manfredi, S. Nassir Ghaemi
Cells interact with each other and with distant stimuli through receptors embedded in their cell membranes, so to preserve their inner integrity and their homeostasis. The receptor ligand-receptor interaction is then transduced in a message to the internal of the cell, which subsequently reacts, providing a response to the environment. What intervenes between the receptor ligand-(the first messenger)-receptor interaction and the response, be the receptor ligand a hormone or a neurotransmitter, is regulated through molecular chains that constitute cascades, termed second messenger cascades. Second (and third, fourth, and so on) messengers are intracellular signalling molecules which are activated within the cell in response to the extracellular-membrane receptor event. Second messengers, once activated, trigger cellular changes in cascades, termed intracellular signal transduction cascades, which regard proliferation, differentiation, migration, survival, apoptosis and, in the case of neurons, depolarization.
Carbapenem-resistant Klebsiella pneumoniae outbreak in a COVID-19 intensive care unit; a case-control study
Published in Journal of Chemotherapy, 2022
Pınar Ergen, M. Esra Koçoğlu, Müge Nural, Mert Ahmet Kuşkucu, Özlem Aydin, Ferda Y. İnal, Hande Öztürk, Ayşe C. Üçişik, Hülya Çaşkurlu, Büşra Güneysu, Büşra Yildirim, Kenan Midilli, Yasemin Çağ, Ferhat Arslan, Haluk Vahaboglu
COVID-19 is a severe viral respiratory infection caused by the novel coronavirus, SARS-CoV-2, which uses the angiotensin-converting enzyme (ACE-2) receptor for cell adhesion [17]. Following cell attachment, a specific transmembrane serine protease (TMPRSS2) cleaves the spike protein, allowing viral RNA to infect the cell successfully [18]. In other words, a permissive cell line should express both the receptor and enzyme. Accordingly, SARS-CoV-2 infects and eventually destroys secretory goblet cells and ciliated lower respiratory tract cells [19]. When the primary protective mechanism of the human lung deteriorates, secretions, microorganisms and debris cannot be excreted and thereby accumulate in the alveolar space [20,21]. Fatal bacterial and fungal infections complicate severe viral respiratory infections, as demonstrated among influenza pandemic victims [22,23].
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