Life-threatening antibodies: The discovery of anaphylaxis.

It was at the turn of the 20th century, that immune serum was found both to save children dying from toxins of deadly pathogens, and to kill a dog within minutes following an injection of harmless doses of sea anemone toxins. This means that, before being formally identified in immune serum, antibodies were already known to be both protective and pathogenic. For this provocative finding, Charles Richet was awarded the 1913 Nobel Prize in Physiology or Medicine.

The function of antibodies.

Antibodies have multiple biological activities. They can both recognize and act on specific antigens. They can protect against and cause serious diseases, enhance and inhibit antibody responses, enable survival, and threaten life.

The immune system as a system of relations.

Progress in neuroimmunology established that the nervous and the immune systems are two functionally related physiological systems. Unique sensory and immune receptors enable them to control interactions of the organism with the inner and the outer worlds. Both systems undergo an experience-driven selection process during their ontogeny.

InterCarb: A Community Effort to Improve Interlaboratory Standardization of the Carbonate Clumped Isotope Thermometer Using Carbonate Standards.

Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth-system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories.

["Immune checkpoint inhibitors in oncology"].

"Immune checkpoint inhibitors in oncology.Cancer immunotherapy has revolutionized oncology. It results from a long history that went along with that of immunology, with its hesitations and failures, and which led to two complementary approaches.

Publisher Correction: Harnessing innate immunity in cancer therapy.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Harnessing innate immunity in cancer therapy.

New therapies that promote antitumour immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. Although these therapies have led to unprecedented successes, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in the next generation of immunotherapy.

Most Earth-surface calcites precipitate out of isotopic equilibrium.

Oxygen-isotope thermometry played a critical role in the rise of modern geochemistry and remains extensively used in (bio-)geoscience. Its theoretical foundations rest on the assumption that O/O partitioning among water and carbonate minerals primarily reflects thermodynamic equilibrium. However, after decades of research, there is no consensus on the true equilibrium O/O fractionation between calcite and water (α).

Lamb dip CRDS of highly saturated transitions of water near 1.4 μm.

Doppler-free saturated-absorption Lamb dips were measured at sub-Pa pressures on rovibrational lines of HO near 7180 cm, using optical feedback frequency stabilized cavity ring-down spectroscopy. The saturation of the considered lines is so high that at the early stage of the ring down, the cavity loss rate remains unaffected by the absorption. By referencing the laser source to an optical frequency comb, transition frequencies are determined down to 100 Hz precision and kHz accuracy.

Basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals.

Background: Basophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, both positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals when aggregated, the ratio of which depends on the concentration of allergen recognized by receptor-bound IgE.

Direct, Precise Measurements of Isotopologue Abundance Ratios in CO Using Molecular Absorption Spectroscopy: Application to ΔO.

We present an ultrasensitive absorption spectrometer based on a 30 Hz/s stability, sub-kHz line width laser source coupled to a high-stability cavity-ring-down-spectroscopy setup. It provides direct and precise measurements of the isotopic ratios δO and δO in CO. We demonstrate the first optical absorption measurements of O anomalies in CO with a precision better than 10 ppm, matching the requirements for paleo-environmental applications.

Trans-inhibition of activation and proliferation signals by Fc receptors in mast cells and basophils.

Allergic and autoimmune inflammation are associated with the activation of mast cells and basophils by antibodies against allergens or auto-antigens, respectively. Both cell types express several receptors for the Fc portion of antibodies, the engagement of which by antigen-antibody complexes controls their responses. When aggregated on the plasma membrane, high-affinity immunoglobulin E (IgE) receptors (FcεRI) and low-affinity IgG receptors (FcγRIIIA in mice, FcγRIIA in humans) induce these cells to release and secrete proinflammatory mediators, chemokines, and cytokines that account for clinical symptoms.

Science Signaling Podcast for 20 December 2016: Trans-inhibition by Fc receptors.

This Podcast features an interview with Marc Daëron, author of a Research Article that appears in the 20 December 2016 issue of Science Signaling, about a mechanism by which an Fc receptor can inhibit signaling by other receptors without aggregating with those other receptors. Engagement of Fc receptors on basophils and mast cells can either activate these cells, which promotes autoimmune and allergic inflammation, or prevent these cells from being activated. Whether these cells are activated depends upon which Fc receptors are present in clusters, because some Fc receptors can inhibit signaling by other Fc receptors that are present in the same signalosome, a phenomenon known as cis-inhibition.

Individual strains of Lactobacillus paracasei differentially inhibit human basophil and mouse mast cell activation.

Introduction: The microbiota controls a variety of biological functions, including immunity, and alterations of the microbiota in early life are associated with a higher risk of developing allergies later in life. Several probiotic bacteria, and particularly lactic acid bacteria, were described to reduce both the induction of allergic responses and allergic manifestations. Although specific probiotic strains were used in these studies, their protective effects on allergic responses also might be common for all lactobacilli.

Innate myeloid cells under the control of adaptive immunity: the example of mast cells and basophils.

Mast cells and basophils are mostly known as the initiators of IgE-dependent allergic reactions. They, however, contribute to innate immunity against pathogens and venoms. Like other myeloid cells, they also express receptors for the Fc portion of IgG antibodies.

Fc receptors as adaptive immunoreceptors.

Most biological activities of antibodies depend on their ability to engage Receptors for the Fc portion of immunoglobulins (FcRs) on a variety of cell types. As FcRs can trigger positive and negative signals, as these signals control several biological activities in individual cells, as FcRs are expressed by many cells of hematopoietic origin, mostly of the myeloid lineage, as these cells express various combinations of FcRs, and as FcR-expressing cells have different functional repertoires, antibodies can exert a wide spectrum of biological activities. Like B and T Cell Receptors (BCRs and TCRs), FcRs are bona fide immunoreceptors.

Computational modeling of the main signaling pathways involved in mast cell activation.

A global and rigorous understanding of the signaling pathways and cross-regulatory processes involved in mast cell activation requires the integration of published information with novel functional datasets into a comprehensive computational model. Based on an exhaustive curation of the existing literature and using the software CellDesigner, we have built and annotated a comprehensive molecular map for the FcεRI signaling network. This map can be used to visualize and interpret high-throughput expression data.

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus.

Background: Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages.