With the advent of “–omics” technologies, there has been an explosion of data generation in the field of toxicology, as well as in many others. As new candidate biomarkers of toxicity are being regularly discovered, the next challenge is to validate these observations in a targeted manner. Tradit ...
Autoimmunity represents a potentially diverse and complex category among the range of adverse outcomes for detection with immunotoxicity testing. For this reason, the risk of autoimmune disease is discussed in this overview chapter with additional mention among the later specific ...
New chemical entities are tested in general toxicity assays during development before entering clinical trials. However, immunosensitization of these entities is not tested on a standard basis. There are no in vitro or in vivo standardized methods available for testing immunosensi ...
Developmental immunotoxicity (DIT) has emerged as a serious health consideration given the increases in the prevalence of many immune-based childhood diseases and conditions, including allergic diseases and asthma, recurrent otitis media, pediatric celiac disease, and type 1 d ...
A brief historical perspective of immunotoxicology is presented describing the early development of predictive screening tests to identify xenobiotics that may cause immunosuppression or skin sensitization. This includes a discussion of the evolution of the discipline to su ...
Inflammation is a complex and necessary component of an organism’s response to biological, chemical or physical stimuli. In the acute phase, cells of the immune system migrate to the site of injury in a carefully orchestrated sequence of events that is mediated by cytokines and acute phase prote ...
Syngeneic murine tumor models have been widely used by researchers to assess changes in tumor susceptibility associated with exposure to toxicants. Two common tumor models used to define host resistance against transplanted tumors in vivo are EL4 mouse lymphoma cells (established f ...
Macrophages are the heterogeneous grouping of cells that are derived from monocytes. They have a multitude of functions depending on their final differentiated state. These functions range from phagocytosis to antigen presentation to bone destruction, to name a few. Their importance ...
Immunotoxicity testing is used to provide safety assessment with the major objective being the avoidance of unacceptable risk of infectious or neoplastic disease. To this end, immunotoxicity testing has employed a variety of host resistance challenge models for measuring both host r ...
Identification of potentially immunosuppressive compounds typically involves assessing a combination of observational endpoints as surrogates for functional endpoints and functional endpoints as surrogates for resistance to infectious or neoplastic disease. Ho ...
A foremost objective of preclinical immunotoxicity testing is to address whether or not a drug or environmental toxicant causes adverse effects on net immune health, expressly the host’s ability to mount an appropriate immune response to clear infectious organisms. Given the complex i ...
Central to the evaluation of potential immunotoxicants is the concept that measurement of multiple parameters is required for the determination of toxicity toward the immune system. A carefully considered integration of endpoints involved in the immune response should be used to de ...
The sheep erythrocyte T-dependent antibody Response (TDAR) evaluates the ability of animals sensitized in vivo to produce primary IgM antibodies to sheep erythrocytes (sRBC). The assay enumerates the number of antigen specific IgM antibody producing cells in the spleen. When exposu ...
The delayed-type hypersensitivity (DTH) assay has a lengthy history in immunotoxicity testing since it was one of the original functional assays included in the National Toxicology Program (NTP) immunotoxicology test panel. Based on NTP data analysis, the DTH assay is among the most pred ...
The method describes production and the selection of neurosecretory PC12A123.7 cells stably transfected with human vesicular acetylcholine transporter (hVAChT). Transfected cells provide postnuclear supernatant used to characterize equilibrium binding of the neur ...
Skeletal muscle plays a key role in regulating whole body glucose homeostasis and severe dysfunction in insulin-mediated glucose uptake is the hallmark of insulin-resistant states and type II diabetes. Therefore it is highly pathophysiologically relevant to perform detailed st ...
ABC transporters have been implicated in a variety of human diseases. The ABCR gene and its protein have been linked to Stargardt’s disease, fundus flavimaculatus, cone–rod dystrophy, retinitis pigmentosa, and age-related macular degeneration. The genetic and molecular pathways i ...
Glucose and related hexoses play central roles in the biochemistry and metabolism of single-cell parasites such as Leishmania, Trypanosoma, and Plasmodium that are the causative agents of leishmaniasis, African sleeping sickness, and malaria. Glucose transporters and the genes t ...
Nuclear magnetic resonance studies of membrane proteins yield valuable insights into their structure and topology. For example, the tilt angle and rotation of the helices in an ion channel can be determined by solid-state NMR spectroscopy in aligned lipid bilayers. Details about the stru ...
The plasma membrane calcium–calmodulin-dependent ATPase (PMCA) is a calcium-extruding enzymatic pump that ejects calcium from the cytoplasm to the extracellular compartment. Although in excitable cells such as skeletal and cardiac muscle cells PMCA has been shown to play only a min ...
