Prenatal Exposure to Pollutants: Influence on the Immune Response
By Roberta Attanasio
The development of the immune system during fetal and neonatal life is negatively influenced by exposure to toxic chemicals, resulting in compromised immune function later in life. An example is fetal exposure to arsenic, which has deleterious effects on the immune response to influenza virus infection in adulthood. Now, results from a new study provide additional evidence for the role that exposure to toxic chemicals early in life plays in shaping the immune response to the influenza virus.
The study (by researchers at the University of Rochester) focused on a mouse model and the chemical 2,3,7,8-tetrachlordibenzo-p-dioxin, or TCDD for short. TCDD, a known carcinogen, is a persistent environmental contaminant usually present in a complex mixture of dioxin-like compounds. It’s a by-product of industrial processes such as pesticide and metal production, waste incineration and wood combustion, and acts via the aryl hydrocarbon receptor, which is present in all cells. The aryl hydrocarbon receptor is a ligand-activated transcription factor that controls the expression of a diverse set of genes.
The researchers designed their mouse study to expand previous epidemiological findings from human studies. These findings showed correlation between maternal exposure to pollutants that bind the aryl hydrocarbon receptor and the decreased ability of the offspring to combat respiratory infections and produce antibodies. In other words, the epidemiological findings indicated that mothers exposed to these pollutants while pregnant may give birth to babies with impaired immune function.
An effective immune response requires the coordinated action of several cell types. CD4+ T cells, one of these cell types, exist in different subsets. It has been known for several years that, by binding the aryl hydrocarbon receptor, some chemicals influence the different subsets of CD4+ T cells, thus resulting in the observed impaired immune function. However, it was not known whether or not prenatal exposure to these chemicals could cause changes in the different CD4+ T cell subsets.
The researchers that carried out the new study wanted to know whether or not fetal exposure to an aryl hydrocarbon receptor ligand (in this case TCDD) directly alters CD4+ T cell differentiation and function later in life. Thus, they exposed pregnant female mice to TCDD and then infected the adult offspring with the influenza virus. The results show that the offspring of the exposed pregnant mothers had a reduced frequency of different subsets of CD4+ T cells when compared with mice born to untreated mothers. In addition, exposed mice produced considerable lower levels of a specific class of antibodies against the influenza virus than control mice.
Then, the researchers transferred CD4+ T cells from the exposed offspring into unexposed mice. They found that, following cell transfer, the unexposed mice responded to influenza virus infection with a reduced number of CD4+ T cells specific for the virus.
CD4+ T cells play a major role in the immune response to a large variety of infectious microbes and are also involved in the development of several autoimmune diseases. Therefore, it is reasonable to speculate that exposure of the fetus to chemicals that bind the aryl hydrocarbon receptor may lead to impaired defense against several infectious microbes and to an increased risk of developing autoimmune diseases later in life.
The use of twin studies in toxicologic research is facinating. Genetics is such a dominating influence in our health and wellbeing, but twin studies offer a wealth of opportunity to clarify the influences of environmental factors on phenotypic expression. Epigenetics, is a fast growing field of research that promises a great deal of insight potential for better understanding of toxicant influence on health through time.
There are many toxic chemicals that are present in many things like insecticides for example. These toxins are very harmful to the human population but even more harmful for the fetal as demonstrated by this paper. Toxins like DDT and TCDD cause harm for the fetal in that either they impair the immune system or cause malformations in the baby. What is so interesting to me is how we introduce so many toxins in many things but we never try to compare the negative effects of these toxins as seen with previous ones. Another thing to take into consideration is the selective toxicity of the chemical toxin to the fetal. There are two important things to always consider in chemical toxins, one being the selective toxicity and second being the period of exposure to the fetal. It has been shown that the first trimester is the most critical period of development for the fetus because this is the time that most of the organs and the nervous system develops. This should also be the time that the mother should avoid any form of toxins as much as possible. Yes it sounds very difficult but its only 18-57 days that the mother has to be the most careful so that her child comes as healthy as possible.
Corporate ‘profit-taking’ only needs us to be alive enough to buy products, it helps to sell products if we have a lot of symptoms to treat (or mask). There is not such an obvious advantage to them to clarify and mitigate causation because symptoms would decline.
Don’t forget the industry geared towards “preventing” disease! Walking into a store like Whole Foods, I believe, gives the perfect experience of what I’m talking about. There are aisles and aisles of ‘natural medicine’ ranging from the ‘oh-so-expensive’ versions to the ‘not-so-expensive’ versions. But what are you supposed to choose? According to one of their online wellness guides for women, there is a list of what I should be taking for my age group. How much should this cost me? As I was trolling through their website I noticed a link for “How to Choose the Best Acne Care + Coupon”. Interesting…so am I choosing the best care product from a list of options or are you pushing me towards a specific product just like Big Pharma? No matter which angle you look at it, either from preventative care to post-treatement, yes @RayKinney, corporate is ‘profit-taking’ and no one cares to clarify and mitigate causation unless a profit can be made.
The EPA’s maximum contaminant level goal for dioxins iszero, but there maximum contaminant level is 0.00000003 mg/L (30 ppq). “MCLs are set as close to the health goals as possible, considering cost, benefits and the ability of public water systems to detect and remove contaminants using suitable treatment technologies”. I understand that the EPA can only do so much, but is there a strict standard that every state must follow when it comes to the specific “technology” and/or “methods” for detection of dioxin contaminants? According to to their website, there is a federal law called the Emergency Planning and Community Right to Know Act (EPCRA) which requires facilities to annually report the release of dioxins. These facilities are only a part of “certain industries” which manufacture, process and/or use a significant amount of toxic chemicals. But this is only once a year! What if they release these dioxins in January, June and September – that is three different incidences of release/exposure and they don’t have to make anyone aware of it until the end of the year? What happens? Do they just pay a fine and say “oops”?
So they make an annual report and they submit it to the EPA. Should we start spending more resources and time on looking at a trickle down effect – perhaps sooner rather than later? We saw beautiful results of dioxin-exposure impact on the offspring of mice exposed “in utero”. How about moving this study more towards human impact and performing a case-control study where at-risk/possibly exposed populations are analyzed and you focus on women that were pregnant, located within a specific parameter, during this dioxin-release time period then perform a prospective cohort study where you follow the children of the before-mentioned pregnant women over time to see the incidence of influenza, respiratory infection and their ability to fight off the infection. Since it is already known that TCDD activates AhR on CD4+T cells then we can begin to look for and categorize children into symptom-based categories such as those exhibiting: allergies, asthma, and organ-specific autoimmune disease(s). Then analyze their CD4+ T cell markers and differentiation-associated cytokines to come to a conclusion of the relationship of TCDD exposure in our local environment and impaired immune function in children exposed to dioxins while in the womb.
Other than having negative effect on fetal and neonatal T cell differentiation, TCDD intoxication also directly affect B cell function and antibody production through cytokine alteration. Studies have shown exposure to TCDD induces gene mutation that suppress antibody production by binding to aryl hydrocarbon receptor. a href=”http://www.annualreviews.org/doi/abs/10.1146/annurev.pa.35.040195.001515?journalCode=pharmtox”>Upon AHR’s binding to TCDD, the downstream pathway alters gene expression and regulation. I think this mechanism contributes to TCDD’s ability to negatively influence fetal and neonatal immune system as well as its tumor promotion function. Besides, as to the production of cytokines, I doubt if the binding of TCDD to AHR relates to the function of NF-kB as it is known that NF-kB is the upstream of a lot cytokines. I haven’t found an effective cure for TCDD intoxication. There are case reports suggesting giving patients methyl-prednisolone and analgesic drugs with antibodies, however, the benefit from the treatment is not significant. Let me know if I am wrong at some point.
It has be perpetuated many times that is insurmountable to eradicate TCDD from our environment, which is conceivably true; however, what we fail to understand is that even though TCDD may not be able to be removed from the environment, its mechanism can be altered in its way that it interacts with the body. TCDD is known to induce oxidative stress, which adversely effects gene regulation by altering the expression of DNA. By identifying TCDD mechanism, researchers are able to gain a better understanding of its effects on CD4+ T cells. TCDD interacts with the secondary lymphoid of the fetus, resulting in T cells not being able to properly differentiate.
Researchers are currently studying preventive measures that will potentially hinder the production of TCDD. From their studies they have identified TCDD to be located in meat (i.e. fat). They suggest for pregnant women to trim the fat from their meat and to consume low fat dairy products. In addition, they suggest eating organically grown products, which are absent of these doxins.
Nevertheless, even though TCDD cannot be completely removed from the environment, it can be better monitored. Therefore, industrial companies need to be better regulated, in order to reduce their emission of doxins.
A study on AhR and Listeria monocytogenes infection in mice found that AhR plays an important role in bacterial infection by promoting macrophage survival (prevents cell death caused by bacterial infection) as well as promoting ROS (reactive oxygen species) production contributing to clearance of the infection. AhR protects against macrophage cell death by inducing expression of AIM in the presence of LXR or RAR ligands. This may be one reason why prenatal exposure to pollutants such as TCDD are impairing the immune system response to bacterial infection. The study also found that adding AIM to macrophages without AhRs also promotes survival. So perhaps a therapeutic approach would be to develop a strategy to deliver AIM directly macrophages and prevent cell death to help clear infection.
AhR has been found to regulate intestinal innate lymphoid cells development/maintenance and function, and also potentially plays a role in human intestinal diseases. AhR expression was found in many types of immune cells in the gut. The environment that the immune cells live in is developed by AhR ligands coming from food or microflora. Dioxins and other dioxin-like compounds can bind and activate AhR as a ligand. Inflammatory bowel disease, IBD, which is caused by IL-17 and IL-22 cytokines secreted by Th17 cells, cause tissue inflammation and damage in the gut. These cytokines are regulated by the AhR transcription factor. A study in the Netherlands observed possible AhR ligands that people can obtain from their food intake. I think pollutants that bind AhR in foods should be more closely studied by researchers. Informed consumers can then direct the market perhaps helping to eliminate toxins such as these.
No doubt that toxins are a major issue to the immune system of adults and prenatal. Toxins in today’s environment should be taken very seriously because such toxins can lead to many mental illnesses. A study that I have come across researched that the aryl hydrocarbon receptor ligand does in fact alter CD4+ effector-cell subsets but demonstrates an increase in regulatory CD4+ T cells. My question is, why is there an increase of regulatory T cells? T cells in general helps fight off any sort of pathogen that have entered the body. If looking at the regulatory T cells, these cells prevent autoimmune disease from developing but they are not presented during the immune responses to a pathogen. If the pathogens are manipulating regulatory T cells to immunosuppress the host, how are they doing this? Regulatory T cells have also been increasing with other types of pathogens presented in the immune system such as HIV and bacterial infections. These pathogens might have something in common in order for these cells to increase within the immune system.
Since TCDD is so toxic to the human immune system and is a known by-product of pesticides, it’s easy to understand the push for “eating organic” that many individuals have adopted in today’s culture. Most dioxins are found in industrial processes but high levels of TCDD are found also found naturally in some soils. One study shows that women who had higher exposure to certain pesticides during pregnancy ended up giving birth to children who had lower IQ scores than children who were not exposed. It is evident the serious problems TCDD pose on the human body if exposed, not to mention the life-long health problems these babies will face as they get older. I think mostly there needs to be more regulation since we know the population’s exposure is currently unpreventable.
Medical research must, out of necessity, oversimplify to try to tease out effects of single toxicants, or at most just a few toxicants at a time. This is very limiting because it masks association and synergy involvement in real world multiple exposure environments that we all have to live in. We are fairly good at clarifying some of the associations, some of the additive effects, and a few of the synergistic effects that are truely causative in nature by their accumulative effects on wellness.Single toxicants are probably never the medical reality of causation except at higher doses that become obviously causative. The multiplicity of concurrent toxicant exposures is where ‘the devil in the details’ hides from applied medical science. As more is learned of the more subtle yet devastating chronic low dose effects of multiple toxicants, we have to try to clarify and treat for causation more than just putting fires out with treatment of symptom abatement. This has to become a paradigm shift quickly to inform the medical and political necessity of a more precautionary approach to how we live in the world, and how we regulate the new chemical products that we disperse around the globe to degrade as pollution. We are going to have to ‘bite the bullet’ and become far more precautionary while we desperately increase the science to reach more comprehensive understanding of how best to provide for public health of our great grandchildren in time.
The body burden levels of the toxic metal lead sequestered in our bones and other tissues, from legacy and current exposures, affects very many physiologic pathways in common with dioxins and many other toxicants. The resultant combined degradations of physiologic functions (neurologic, immune, etc.)are the devil in the details.
There is no way to escape pollutants, I agree with many other readers. If one chemical gets regulated and gets somewhat out of the way, another new one comes, it’s an endless cycle. What we have to change – and it’s impossible to do – is our culture of profit at all cost, at the expenses of everything else. There must be a way to combine progress with respect for the environment, but as of now this way seems to elude our world. Awareness of the problems is not sufficient, as profit will dictate how to move on even in the face of awareness of the enormous damage caused by the indiscriminate release of toxicants, with no control and no assessment done. At the moment, I don’t see any way out, but I hope there is a little star hidden somewhere in the sky that eventually will shine and make everyone realize that we can do way better than this.
Awareness and research are not considered to be the only solution for eliminating or reducing exposure to toxic chemicals. However, these are valid parts of the whole solution to this global health issue. People should certainly be more informed about the serious ramifications that result from exposure to harmful chemicals. Maybe that would motivate them to demand that the government, science and medicine work swiftly and effectively together to formulate better ways to control pollutant exposure. It has been proven that there is strength in numbers, and the more people that bring the issue to light the more likely that change will occur. In order for change to happen it has to be fully understood that there is actually a problem. Performing more research on the effects of exposure to these chemicals will also help evoke change. The research is the scientific and medical proof that can be used as supporting evidence that this issue is real and needs to be handled immediately. If more people truly understood the devastation that pollutants can cause to them now and in the future, I am convinced that we would see significant progress made toward resolving this problem.
Mila A., I couldn’t agree with you more. But as Rachel M. stated, we ultimately have to wait on the government for any regulations limiting our exposure to these chemicals. What will it take to persuade our lawmakers to enforce stricter regulations on chemical production and distribution? An endless amount of information is available proving the dangers associated with chemical exposure, but as individuals we can only do so much to protect ourselves from the negative side effects. One organization known as the Environmental Working Group, or EWG, is working to incorporate scientific data with chemical reform to protect our population from toxic pollutants. Unfortunately, the structure of our government is very hard to persuade, and millions of Americans are left in the dark, unable to prevent their exposure. Isn’t our government supposed to protect us? Unfortunately, the chemical industry is a multitrillion-dollar industry, and has a larger influence on government policy than the voice of common Americans. Money is apparently more important than our health, and something has to change soon to influence American politics to ultimately protect our health and well-being. Studies that provide detailed mechanisms of the toxic effects of pollutants like arsenic and TCDD such as these should alarm the public of the dangers that are caused by exposure to chemicals. If our government isn’t going to reform their policies on chemical production and distribution based on scientific research that has proven their detrimental impacts on health, how can we avoid them? Elaine Shannon of the EWG explained in an article that, “federal regulators must confront a mass of incomplete but worrisome evidence and decide whether it’s time to say that the chemical’s risks to people, especially babies and children, outweigh its benefits.” Scientific research is our light at the end of the tunnel, and we can only hope that increased awareness of these dangers will someday make a difference.
What the Chemical Industry Doesn’t Want You to Know
I agree with you that scientists need to “oversimplify” their research, but the issue is granting funding for this research and not “stepping on the toes” of those making the most money for our government. But what really happens when scientists discover negative causal associative effects regarding toxicants we are regularly exposed to on a daily basis? Sure you might see a short-period of “news-worthy” media attention, but normally this is where it stops. When the average person hears about the dangers of something that they encounter on a regular basis they normally change their habits or try to avoid the danger for a short period of time, but for the majority of persons (not all) they seep back into the habit of the aforementioned exposure to danger. The average medical doctor, in my opinion, does not take this new information into account when practicing medicine on their patients. I rarely see medical practitioners campaigning for public awareness regarding how, when, where to avoid toxicants in our daily lives. This precautionary approach that you speak of is necessary and its necessity has been stated among many audiences — but when will we see this put into action? I guess we have to wait on the government for that answer.
It is somewhat encouraging that the glacialy slow process of change after the science finally sinks into the social arena actually was able to greatly reduce exposures to lead in house paints, gasoline, and many household products such as miniblinds and childrens toys. It only took since roman times to influence some oversight via regulation changes on industry. Yet, we still dump many tons of lead fishing sinkers into water that disolves lead and poisons fish and supportive species… and tackle-box contamination from lead sinkers rolling around transfering particulate lead onto hands, lunches, caught fish, and clothing to take home to pollute the frying pans and surfaces that the baby crawls around on. Another thousand years and maybe we will get it together to figure out that we really could figure out some other less toxic way to weight fishing lines…. but by that time we probably will not very many fish… because we are poisoning them anyway… so perhaps the NRA will still win out over the next millenium.
You bring up a great point – our consumption of fish. According to a report from June of 2013, published by the Earth Policy Institute, farm raised fish production overtakes beef and even wild-caught fish. The US commonly farms tilapia, catfish, barramudi, striped bass and rainbow trout. These farmed-fish are normally regarded as a “safe alternative” that is eco-friendly and perhaps even “green”. So maybe the NRA is not winning after all? Who am I kidding – they still are winning. The warnings of farm-raised fish is something that I have seen a lot lately, particularly on Facebook, that eating Tilapia is worse than eating bacon.
But is this really a safe alternative to wild-caught fish, are we really “avoiding” pollutants like dioxins? Tell me, who is monitoring these waters for dioxin contamination and when contamination does occur, is it too late? Have shipments to local grocery stores already been made and how many people consistently stay on the look-out for a “recall” sign regarding foods they normally consume when they go to the grocery store? Farm-raised fish may bring about a whole other set of problems in regards to strict regulation, dioxin consumption and effects on our health. More specifically, as stated by this blog article, an increase in autoimmune disease as a result of disruption in adequate and functional CD4+ T cell differentiation. What if the fish are being farmed in an area where run-off drops off into their habitat water and that run-off contained a multitude of pollutants? So this all adds to the problems that you listed and then imagine, like you said, we go home and cook it on non-stick surfaces and we perpetuate the cycle of pollutant consumption! We, as a society, are already aware that TCDD persists and accumulates within our food chain, most notably in the fat of vertebrate species, therefore it should be of major concern that food be regulated on a higher level. But it should not just encompass the animals that we feed on, it should encompass ingredients of their feed, their local habitat soil and/or water contaminants and testing of their local watershed. The FDA does allow a specific level of TCDD for pesticides and other synthetic organic chemicals; more specifically, 3 x 10^-8 (0.00000003) mg/L. It does not seem like a very high level when you first look at it, but what about constant exposure at low levels from one or more sources? How does that effect add up? A horrendous example of food contamination with TCDD that I found — closely related to the topic of this article — had to do with the US FDA determining that TCDD had been found in chicken-containing baby foods. So instead of just worrying about the surfaces that babies crawl on, in addition to pollution exposure in the womb, we now have to worry about food prepared specifically for them in the early stages of their life – outside of the womb. This time in development is so critical on so many different levels. This information came from the US FDA’s annually conducted total diet survey conducted during the last half of 1997 through the first half of 1998. It was discovered that TCDD and other PCDDs (polychlorinated dibenzodioxins) were in a feed additive called ball clay. This ball clay was used as a flowing agent (aka anti-caking agent) during the production of soybean meal that was used to feed pellets given to chickens, catfishes, and cows — popular for use during the 1990s in the US southern states. This also ties back to farm raised fish! Fortunately, the US FDA intervened and stopped further distribution of this contaminated soybean feed in early June of 1997, but contaminated chicken products (used in the baby food) that was processed before this intervention could still be found in products being sold in retail outlets. It took them 3 years to announce a revised guidance for industry use of dioxins as a part of anti-caking agents used in animal feeds production. My problems with this guidance is that first of all it took 3 years to notify feed industry manufacturers AND it was not a document stating that use needed to stop; instead, it was a document offering “general
advice regarding monitoring of these products”. According to an informative FDA web page, last updated on 06/05/2014, “There are no tolerances or other administrative levels established by the FDA for dioxins in feed”.
The issue of awareness and its short-term effects are probably due to the symptoms that TCDD causes. An impaired immune system due to external, non-genetic factors is something that most people may not understand. An impaired immune system is not as obvious as physical defects in other diseases such as fetal alcohol syndrome. While researchers may simplify the findings to laymen, there is ultimately something lost in translation because the laymen do not have the same immunological background. This lack of understanding of how TCDD affects fetal development will always be a problem unless TCDD is implicated in more severe and obvious physical phenotypes. Some of the more severe physical phenotypes that TCDD may cause include lethality, wasting, lymphoid and gonadal atrophy, chloracne, hepatotoxicity, adult neurotoxicity, and cardiotoxicity at high levels of TCDD exposure and cleft palate and hydronephrosis at low levels. Although some may argue that TCDD levels may never reach those levels, the low dose exposure causing those symptoms may be enough to cause concern for pregnant mothers. This may be the “angle” that you would want to earn grants for TCDD/AhR/CD4+ T cell effects.
Prenatal exposure to dangerous chemicals such as Arsenic and TCDD(dioxin)is a very serious public health issue that we must continue to bring awareness to. I believe doing research that provides vital information about these chemicals and their adverse effects is a key component to solving this problem. However, the knowledge we obtain has to be applied in order to make a significant difference. Of course in an ideal world, we would not be exposed to TCDD, but since we are regularly exposed to this toxic chemical we must learn as much as possible about it. TCDD the is most toxic of all of the dioxins, and therefore has been the most studied. Yet, we still have not figured out how to eliminate it or at least its adverse effects on the body. There have been several studies done on the Ah receptor and dioxin. One study stated that Ah receptor control is dependent on the tyrosine kinase c-Kit, and the transcription factor Notch. Maybe if c-Kit and Notch were inhibited somehow, we can eliminate or reduce the effects of TCDD on the immune system. . In the meantime, there are some precautionary steps that we can take to limit dioxin exposure such as proper incineration of contaminated material,good controls and practices of food production that will make sure food is dioxin free, and eating a healthy well-balanced diet can also help reduce dioxin exposure. The research must continue about this major public health issue, as well as the conversation and the awareness.
Reference: Bock, Karl Walter, The human Ah receptor: hints from dioxin toxicities to deregulated target genes and physiological function, 2013
I agree, TCDD is an extremely toxic dioxin, and there are other environmental toxins that are just as harmful such as Polychlorinated biphenyl (PCB)- Which has a similar structure and toxic mode of action as this dioxin. Similarly to dioxin, PCB is an Ah-R agonist; therefore, exposure to this toxin can also result in alterations in cellular growth and function. Not surprisingly, comparable to dioxin, PCB also hinders many biological functions, including the nervous system, endocrine system, and the immune system. The fetus is reported to be extremely vulnerable to toxic effects of PCB. Studies in human populations reveal that neonates who were exposed to PCB during fetal development exhibited atrophy of the thymus gland, the organ responsible for lymphocyte maturation. The same studies report that children who were exposed to levels of PCB demonstrated a decreased antibody response to diphtheria toxoid at 18 months of age, a decreased response to tetanus toxoid at 7 years of age, reduces MMR reactivity after vaccination, and increased incidence of ear infections.
My question is about the specific subsets of CD4+ T cells. Looking at the study I see that they looked specifically at Th1 CD4+ cells and Tfh CD4+ cells. They mention that these two are significantly diminished. This leads me to believe that this is pushing us towards Th2 CD4+ cells which are linking to allergies and hypersensitivity. This could mean that people subjected to TCDD might be more prone to allergies and asthma. Perinatal exposure of mice to TCDD decreases allergic sensitisation through inhibition of IL-4 production rather than T regulatory cell-mediated suppression./a> This study shows that Th2 CD4+ cells are suprisingly being suppressed as well. Those with TCDD exposure show a complete lacking in allergies. They theorize that Treg cells are not suppressed by TCDD. T lymphocytes are direct, aryl hydrocarbon receptor (AhR)-dependent targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): AhR expression in both CD4+ and CD8+ T cells is necessary for full suppression of a cytotoxic T lymphocyte response by TCDD../a> This study shows that cytotoxic CD8+ T cells are also suppressed by TCDD. We are looking at at least partial suppression of the adaptive immune system. This leads to relying solely on the innate immune system for defense against all pathogens.
TCDD is a compound found in the infamous chemical known as Agent Orange. Numerous studies have shown that it caused birth defects to the offspring when the parents were exposed. ahR when bonded to compounds such as TCDD, initiates transcription factors forming enzymes such as cytochrome P450 which is used to metabolize toxic compounds in the body. Time of exposure is also critical as one study pointed out The study posted above focused only on CD4+ cells, but what about CD8? Since it is a viral infection, they should have also have focused on CD8 activation helps fight off viral infected cells. While most studies focused on the phenotype of a disorder, we must not forget that it is the subtle changes in the genotype is causing the disorder.
Exposure to TCDD may now be unpreventable, but was this class of chemical not greatly increased into the environment by production and dispersal of herbicides across the land?
Doesn’t this call out for better precautionary measures from society when allowing the production of 85 thousand chemicals, many of which are largely new to the world environment, new to breastmilk, and new to the unborn? Current science is well capable of doing a far better job of ecotoxicologic assessment of proposed products BEFORE wide dispersal around the globe. Very little adequate testing has been done on any but a few hundred of the 85K chemicals released into the environment. Should we not require testing adequately prior to massive production and dispersal? The emerging science of epigenetics is already demonstrating very serious implications for future generations. we had better think long and hard about our responsibilities to our great great grandchildren.
I agree, most toxicants are unpreventable because they are so common in the environment, seen and unseen. We as a generation have focused on present earth so much that we have forgotten about the future. There are critical periods during fetal development that is critical to determine birth outcomes. Not to mention, birth outcomes are not only limited to exposures after conception.In article Prenatal Exposures states in males can affect sperm quality and egg development in females affecting fetal development. What we do today can cause major consequences to our offspring to come. The authors in Prenatal environmental exposures, epigenetics, and disease.html have introduced great implications that many chemicals are endocrine disruptors and other xenobiotics acting in a combination with genetics to adversely affect human health from birth through to adulthood. This suggests that epigenetic dysregulation is possible and how autoimmune diseases are common. Overall the present generation is putting future offsprings at risk for multigenerational diseases generations before conception. So we can not escape our genes and genetics play a vital role how our immune system is developed.
C:\Users\University Library\Downloads\Prenatal Exposures A continuum of vulnerability to environmental toxicants PSR.html
C:\Users\University Library\Downloads\Prenatal environmental exposures, epigenetics, and disease.html
My question was: How come the binding to aryl hydrocarbon receptor (Ahr) influences the subset of CD4+ T cells? and what I found is that this receptor plays a role in cell development and the adaptive response in our body. Ahr is involved in the differentiation of many developmental pathways including the differentiation of CD4+ T cells in our body that will later be activated as TH1 or TH2, each one performing different roles in the immune response. Control of T cell differentiation by the aryl hydrocarbon receptor On the other hand, this receptor is also the one who will recognize toxic chemicals like Arsenic. Now, Arsenic is not the only chemical that could cross the placenta and harm a developing baby. According to a study, mercury, cadmium, and lead are well known metals that could also cross the placenta. The role of the placenta in fetal exposure to heavy metals For example, prenatal mercury exposure can have detrimental impacts on the baby’s immune system since it decreases B cell proliferation (antibody making process) increasing susceptibility to diseases on the first months of age of the baby. Decreased immune response: sublethal doses of mercury Because of all these facts, prenatal chemical exposure should be highly informed to our community. Toxic Substances Control Act, or TSCA should step up and eliminate some unsafe chemicals because this does not only affect pregnant women; it also affects the public in general.
The population’s exposure to TCDD is unpreventable. TCDD is found throughout our environment. Small traces of TCDD can be found in our fish, meat, and dairy products. In the study, researchers knew from previous research that the binding of aryl hydrocarbon receptors can cause changes in function of CD4+ T cells however, they didn’t know the mechanism that would cause changes in the immune system. The activation of AhR will only decrease the number of CD4+ T cells responding to the site of infection but it doesn’t affect CD4+ T cells ability to differentiate. Eliminating TCDD from the environment isn’t a feasible task therefore researchers should figure out the mechanism behind TCDD and how activation of AhR can be inhibited. It is when AhR is activated that it decreases antibody responses. Reactive oxygen species (ROS) is one of the byproducts of TCDD that makes it so toxic. Once researchers figure out how to inhibit either the activation of AhR, prevent the binding of TCDD to AhR, or understanding the role of ( ROS ) then we can possibly prevent the adverse effects of TCDD on the immune system.
You have a great point about how there needs to be more research on ways to figure out how to stop the binding of AhR to TCDD. The abundance of chemical toxins in our daily life increases our exposure to these toxins and their harmful effects. If we had more research that went in finding ways to limit the negative effects of these toxins to our immune system then they would not pose a danger for us. While searching for some answers to how we can stop AhR binding, I found some interesting studies that have been done to try and find a way to stop this process. One research showed how resveratrol present in many plants binds the aryl hydrocarbon-induced tumorigenesis in mice. Binding and activation of AhR by TCDD causes many reactions including toxicity, teratogenicity, and cancer. Therefore, it is very important to find ways to prevent the binding of the AhR with TCDD.