Veterans and Agent Orange Update 11 (2018) (2018) / Chapter Skim
Currently Skimming:
6 Immune System Disorders
6 Immune System Disorders
Pages 195-212
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 195... ...
and any specific diseases involving immune suppression, allergy, autoimmunity, or inflammation. Immune-system disorders affect more than 23.5 million Americans (NIEHS, 2012)
|
From page 196... ...
. Most times, immune suppression manifests itself as an increased incidence of infections or an increased risk of neoplasia.
|
From page 197... ...
, it is often difficult to obtain clinical evidence that directly links chemically induced changes in immune function to increases in infectious diseases or cancers because many confounding factors and effect modifiers can influence a person's ability to combat infection. These factors include age, vaccination status, the virulence of the pathogen, the presence of other diseases (such as diabetes)
|
From page 198... ...
Other systemic autoimmune diseases also occur. Systemic lupus erythematosus is an autoimmune disease in which multiple organs are targeted by a variety of autoantibodies.
|
From page 199... ...
The adaptive immune response follows with specific antibodies and cell-mediated immunity that add to the inflammatory process. Interactions among innate immune cells and epithelial and endothelial cells are important in regulating the magnitude of inflammation, and improperly regulated inflammation can contribute to diseases that arise in non-lymphoid tissues, such as the lungs, skin, nervous system, endocrine system, and reproductive system.
|
From page 200... ...
-α. A few studies also included disease or condition endpoints, such as rheumatoid arthritis, systemic lupus erythematosus, immune suppression, and sensitivity to fungal infection.
|
From page 201... ...
Some early studies of the Quail Run Mobile Home Park population who were exposed to TCDD-contaminated soil reported that dioxin exposure was associated with a reduction in a specific type of cell-mediated immune response, the delayed type hypersensitivity response (Andrews et al., 1986; Hoffman et al., 1986; Knutsen et al., 1987; Stehr-Green et al., 1987)
|
From page 202... ...
. After adjusting for mercury blood level, race, menopausal status, diet, and BMI, total TEQs for PCBs were significantly associated with antinuclear antibody positivity for each quartile compared with the referent group, and the overall trend was significant (p < 0.001)
|
From page 203... ...
Cases in which disease-modifying antirheumatic drugs or other medications for rheumatoid arthritis were identified were considered to be probable instances of rheumatoid arthritis, and those individuals for whom a medical record review allowed confirmation of the diagnosis were considered to be definite cases of rheumatoid arthritis. Surveys collected information on age, tobacco use, menopausal status, childhood farm exposure, non-specific household and specific farm pesticide exposure, farm activities related to pesticides and other activities such as sun exposure, exposure to solvents and exposure to pesticides through mixing or application.
|
From page 204... ...
(2016) performed a retrospective study of 331 male electric arc foundry workers at a single plant in Trentino, Italy, to determine if they had experienced excess mortality from all causes or were at an increased risk for several other diseases, including rheumatoid arthritis, due to occupational exposures to foundry dust.
|
From page 205... ...
(2017) , studied serum TCDD levels, the expression of AHR, and a variety of pro-inflammatory cytokines in Vietnamese who were either exposed or not exposed to TCDD-like chemicals.
|
From page 206... ...
While the levels of proinflammatory cytokines were significantly elevated in the exposed population, they did not correlate with serum dioxin levels. While there were more cases of rheumatoid arthritis in the exposed population than in the general population, neither the dioxin levels nor pro-inflammatory cytokines were compared between exposed people with and without rheumatoid arthritis.
|
From page 207... ...
TCDD-induced immunotoxicity is due primarily to changes in adaptive immune responses resulting in the suppression of both antibody-mediated and cell-mediated immunity. Dioxin and other AHR agonists may also reduce the clearance of infections and promote tumor growth through alterations in immune function.
|
From page 208... ...
These data show that pluripotent hematopoietic human cells express AHR and that AHR agonists enhance erythroid differentiation, whereas the antagonism of AHR favors the expansion of megakaryocyte cells. This finding supports previous work indicating that B-cell activation results in increased AHR expression and that an exposure of B-cells to benzo[a]
|
From page 209... ...
, providing a suggestive mechanistic link between TCDD exposure and some lymphomas. Cellular immunity, which is mediated by the thymus and T cells, is also a target of TCDD and dioxin exposure and the AHR pathway (Baricza et al., 2016; Feng et al., 2016; Kuwatsuka et al., 2014)
|
From page 210... ...
Thus, depending on the disease, TCDD exposure could exacerbate or ameliorate symptoms. SYNTHESIS Previous VAO committees have concluded that the data were inadequate or insufficient to support an increased risk of immune suppression, allergy, or autoimmune disease.
|
From page 211... ...
It is biologically plausible for dioxins to influence immune dysfunction, but because of the variety of methods and endpoints used in studies to date, it is hard to confirm specific mechanisms by which the COIs induce immune suppression and auto-immunity. TCDD has been shown to suppress both limbs of the adaptive immune response, reduce the clearance of infection, and promote tumor growth (Bruhs et al., 2015; Kerkvliet, 2009, 2012; Kreitinger et al., 2016; Marshall and Kerkvliet, 2010)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.