Immunotoxicity

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Immunotoxicity is defined as the adverse effects of foreign substances xenobiotics on the immune system. Two types of effects are possible: immunosuppression which may result in an increased susceptibility to infection or to the development of tumours and immunopotentiation which may manifest as an allergy or as autoimmunity. There is, as yet, little evidence that well controlled occupational exposure to industrial chemicals has led to clinically significant immunosuppression. In contrast, a number of industrial chemicals have been shown to cause immunopotentiation in exposed populations, producing occupational asthma and contact dermatitis and possibly autoimmunity. In experimental models, immunosuppression usually assessed by in vivo or in vitro immune function tests has been induced by a wide range of chemicals but there are a few reports of the immunosuppression leading directly to an increased susceptibility to infection or to the development of tumours. Predictive experimental models are available for type IV allergic reactions, but the identification of chemicals that have a potential to cause other types of allergy or autoimmune reactions requires further research and the development and validation of new animal models. It is considered that routine subacute and chronic toxicity studies should include a full gross and histopathological assessment of the lymphoid organs to more accurately detect the potential of a chemical to cause immunotoxicity.

Immunotoxicity

Federal government websites often end in. The site is secure. The immune system defends the body against certain tumor cells and against foreign agents such as fungi, parasites, bacteria, and viruses. One of its main roles is to distinguish endogenous components from non-self-components. An unproperly functioning immune system is prone to primary immune deficiencies caused by either primary immune deficiencies such as genetic defects or secondary immune deficiencies such as physical, chemical, and in some instances, psychological stressors. In the manuscript, we will provide a brief overview of the immune system and immunotoxicology. We will also describe the biochemical mechanisms of immunotoxicants and how to evaluate immunotoxicity. Lymphocytes, neutrophils, macrophages, eosinophils, and basophils are the main players. A multipotent stem cell gives rise to either a myeloid stem cell or a lymphoid stem cell. Eosinophils, basophils, and neutrophils arise from myeloblasts through granulocytopoiesis. Myeloid stem cells also give rise to monoblasts, which become monocytes and later on macrophages through monocytpoiesis. Lymphoid stem cells give rise to B-cells, T-cells, and natural killer cells. The primary organs are the bone marrow where immune cell production and B-cell maturation take place and the thymus where T-cell maturation takes place. The secondary organs allow immune cells to interact with antigens.

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Direct immunotoxicity comprises chemical-associated immunosuppression and chemical-associated immunostimulation. Immunosuppression is the consequence of toxic effects of exposure to chemical on components of the immune system. Such effects may lead to decreased resistance to infections and tumours. Classically, this condition has been studied in animal models, but epidemiological studies have been carried out and shown such effects of environmental pollutants in the population. Currently, also in vitro techniques are being developed to study such effects. Chemical-associated immunostimulation is often a consequence of direct toxicity to components of the immune system, resulting in a lack of regulation. This may occur for instance by exposure to fine dust particles.

These immuno-toxicants affect both innate and adaptive immunity, and further activate numerous signaling pathways that are regulated in cancer and autoimmune disease. Presently, immunotoxicity is assessed by relying on different in vitro and in vivo models, utilizing high throughput immune-assessment assays or techniques. Advancements in the management of life-threatening disease may lead to an increase in immunotoxicity. Immunotherapies such as immune checkpoint blockade and chimeric antigen receptor CAR T cells therapy have taken the frontstage in the treatment of life-threatening diseases such as cancer and autoimmunity. Besides innovative management, immunotherapy has obvious complexity and uncertainty due to antigenic heterogenicity, moreover the resistance mechanism needs to be determined. To meet the demand for innovative tools, certain agents have been restructured for cancer treatment. However, upon further review, it is important to consider that these modifications could potentially lead to inflammatory diseases, exacerbating pre-existing conditions and compromising immune regulation. Significantly, various immunotoxins are not effectively scrutinized through standard screening procedure for immunotoxicity and thus the most important immune vulnerabilities remain unanswered. To understand such immune system complexity, there is a need to standardize more predictive assessment protocol for targeting the distinct vulnerabilities of the perinatal immune system compared with the fully matured and dispersed immune system of the adult.

Immunotoxicity

Immunotoxicology sometimes abbreviated as ITOX is the study of the toxicity of foreign substances called xenobiotics and their effects on the immune system. Consequences of xenobiotics affect the organ initially in contact often the lungs or skin. The study of immunotoxicology began in the s. In recent years, guidelines and laws have been created in the effort to regulate and minimize the use of immunotoxic substances in the production of agricultural products, drugs, and consumer products. Immunotoxic agents can damage the immune system by destroying immune cells and changing signaling pathways. Some common agents that have been shown to cause immunosuppression are corticosteroids , radiation, heavy metals, halogenated aromatic hydrocarbons, drugs, air pollutants and immunosuppressive drugs. This can be measured by decreased IgM and IgG antibody levels which are an indicator of immune suppression.

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Chemical-associated immunostimulation is often a consequence of direct toxicity to components of the immune system, resulting in a lack of regulation. Distrutti E. Gut Microbes. Staples J. The shift to a Th2 response promotes expression of Th2 cytokines, the most important being IL-4, and expanding the production of immunoglobulins, especially IgG1 and IgE [ ]. A pesticide, whether insecticide, herbicide, or fungicide, is any substance used to kill, repel, or control specific plants or animals [ ]. Aster R. Chou M. The role of the glucocorticoid receptor in inflammation and immunity. On the other hand, the adaptive immune response is much more intricate. PGD2 induces eosinophil infiltration and smooth muscle contraction.

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Cox L. Toporova L. This may occur for instance by exposure to fine dust particles. Nevertheless, the results further showed that atrazine also inhibited dendritic cell maturation, as suggested by the decrease in the proportion of mature splenic dendritic cells DC; CD11chigh [ ]. Shini S. Hari Y. They further proved that the fertility of these mice was reduced and if mating occurs, these effects can be transmitted to subsequent generations [ ]. Therefore, it is of no surprise that pregnant woman will have a Th2 dominated response because of their high estrogen levels and are more prone to Th2 mediated disease, whereas girls in their prepubescent years with low estrogen levels will be more prone to Th1 mediated diseases [ 48 ]. Published online Jul When mice were subjected to organo-chlorine, a shortened disease-free time was observed, which confirms that EDCs accelerate the development of autoimmunity [ ]. It has been shown that the powerful immunosuppressive drug cyclosporin A CsA , inhibits the synthesis of certain T lymphocyte cytokines at the level of gene transcription [ ]. Casale G.