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Prenatal Exposure to Pollutants: Influence on the Immune Response
Nov30

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...

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Sex Differences in the Immune Response to Vaccines
Feb11

Sex Differences in the Immune Response to Vaccines

By Roberta Attanasio Women and men respond differently to infectious microbes and vaccines – it is said, indeed, that the immune system of women is stronger than the immune system of men. Stronger or weaker, one thing is certain – men and women are not the same in terms of immune response. A few years ago, the journal Lancet Infectious Diseases published “ The Xs and Y of immune responses to viral vaccines” – a comprehensive article that clearly shows how the biological differences between sexes influence the immune response to vaccines, as for example the influenza, yellow fever and hepatitis vaccines. There are not many published studies on the same subject, though. The majority of scientists involved in vaccine research do not consider sex as a variable and, typically, vaccine trials are not designed to take into account the physiological differences that exist between men and women. If we had to take these differences into account, how would things change when vaccinating human populations? In the New York Times article “Do women need such big flu shots?” Op-Ed contributors Sabra Klein and Phyllis Greenberger provide an example related to one of the influenza vaccines: “Under the current guidelines, men and women are to get equal-sized doses of the H1N1 vaccine. Yet women’s bodies generate a stronger antibody response than men’s do, research shows, so less vaccine may be needed to immunize them. If we could give women a smaller dose, there would be more vaccine to go around. And we might also spare them the mild side effects that vaccines can cause, like pain at the injection site, inflammation and fever. All of these are more common in women than in men.” In 2010, the World Health Organization published “Sex, Gender and Influenza”, a report that “focuses on the different effects of seasonal epidemics, pandemics and localized outbreaks of influenza on males and females including pregnant women.” The report concludes that “significantly more research is required to gain a more complete understanding of the complex and varied effects of sex and gender on influenza infection and vaccination, and underscores the need to consider their interplay with any infectious disease of global concern.” However, there are still large gaps in our understanding of how sex differences influence the immune response to vaccines and not enough research is done to fill these gaps. May be, step by step, we’ll get there. Meanwhile, here is one of the steps – a new study found that high levels of testosterone make the immune response to the flu vaccine go south. The study – “Systems analysis of sex differences reveals an immunosuppressive role for...

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H7N9 Influenza Virus: Ethnicity and Protection from Infection
Jan29

H7N9 Influenza Virus: Ethnicity and Protection from Infection

By Roberta Attanasio In March 2013, a new flu virus — the H7N9 — was identified in China. By early May, before retreating and disappearing, it had infected 131 people and killed 26 of them.  However, less than two weeks ago (January 17), the New York Times reported that “China is disclosing a steadily growing number of cases of H7N9 bird flu, including four more cases announced on Friday, reviving concerns among health experts that the disease may be spreading and could pose a further threat as the world’s largest annual human migration begins ahead of Chinese New Year.” The H7N9 virus is a “reassortant” — it includes combined elements from three distinct viruses. People acquire the virus mostly from exposure to infected poultry. As of today (January 29, 2013), the World Health Organization states that there is no evidence of sustained person-to-person spread of H7N9. No cases of H7N9 infection have been reported outside of China. According to the Centers for Disease Control and Prevention (CDC), “It’s likely that sporadic cases of H7N9 associated with poultry exposure will continue to occur in China. Cases associated with poultry exposure also may be detected in neighboring countries. It’s also possible that H7N9 may be detected in the United States at some point, possibly in a traveler returning from an affected area. Most concerning about this situation is the pandemic potential of this virus.” During pandemics, which are caused by the worldwide spread of infectious microbes, different human populations respond differently to the infection, most likely because of specific differences in factors related to their immune system. Is this also true for the H7N9 virus? Should we expect differences in the susceptibility of different populations to infection? An international team of investigators from institutions in Australia, Singapore, the U.S. and the U.K. report, in an article recently published by the journal Proceedings of the National Academy of Sciences USA (January 21, 2014), that different human populations may indeed vary in their susceptibility to H7N9 infection. The article is titled “Preexisting CD8+ T-cell immunity to the novel H7N9 influenza A virus varies across ethnicities” and presents results related to several ethnic groups, including Caucasoid, North American natives, Oriental, African, Amerindian, Alaskan Yupik and Australian Aboriginals. Because H7N9 is a “new” virus, the immune system does not have memory of it and it is not ready to quickly produce neutralizing antibodies — which protect from infection or severe disease — when it encounters the virus. In absence of neutralizing antibodies, the human immune system relies mostly on a type of killer cells — called cytotoxic T lymphocytes — for protection against the virus.  These lymphocytes kill cells infected with the virus...

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