Context: Immune system: Dendritic cells are 'the watchers' for the immune system. They communicate with other immune cells directly or remotely (via cytokines) to bring evidence of foreign invaders -- molecules called antigens -- to helper T cells and other immune system defenders.
Bringing the antigens to helper T cells provokes an immune response. The dendritic cells capture antigens, take them apart and show pieces of the invader to the helper T cells. The activated T-cells then release their own specialized fighters to combat infections, allergens or other intruders.
Immune cells use cytokines (long-distance signaling molecules similar to hormones) to talk to each other and alter immune responses. The combination of cytokines released by dendritic cells determines what kind of T-helper (Th) cells dominate an immune response. A Th1 response prompts the killing of infected cells, and thus a local immune response (cellular immune system). A Th2 response promotes B-cells to produce antibodies and invoke a body-wide response (humoral immune system). Asthma and other allergic reactions are typically Th2 responses.
A balanced immune system responds to foreign antigens without producing a reaction to the host tissues. An unbalanced, or hypersensitive, immune system over-reacts to low levels of antigen, or to the host itself. In these cases, small amounts of pathogens and allergens heighten the immune reaction, which can cause a bevy of typical allergic symptoms, including swelling, sneezing and rashes. Each subsequent exposure to the allergen increases the immune response and reaction, thus their hypersensitivity to that substance.
One kind of hypersensitivity, called type 1, increases production of the immunoglobulin E (IgE) antibody. Each person has unique types of IgEs based on past exposures and genetic makeup.
Context: Asthma: Immune systems in people with asthma and allergies react more vigorously to allergens than the immune system of someone without the conditions. Asthma is a chronic allergy affecting the ability to breathe. During an asthmatic attack, an allergen, such as pollen or dust, triggers an immune response. The airways (the trachea and bronchial tubes) narrow as mucus accumulates and muscles tighten. Breathing becomes difficult, and the asthmatic person wheezes and gasps for air.
About 20 million Americans have asthma; 9 million of them are children. The rate of diagnosis of asthma increased dramatically in the last few decades (American Academy of Allergy, Asthma and Immunology). The nature of the increase continues to perplex scientists.
In the US, asthma affects minorities and those of low socioeconomic status disproportionately, (CDC). African-American and Hispanic children have asthma emergency room visits at rates two to four times higher than Caucasian children (American Academy of Allergy, Asthma and Immunology). The increase in asthma rates worldwide is linked to increased economic development and consequent urban living, suggesting there are elements of city life that might predispose children to develop the respiratory disease (Environmental Health Watch). More on asthma...
Context: Lead: Societal and regulatory changes in the US have reduced environmental lead exposure since the 1970s when the heavy metal was removed from gasoline and lead soldering. Yet, it remains a health threat in some locations.
A long-term government study called the National Health and Nutrition Examination Survey (NHANES) has monitored lead levels in the US since the 1970s . As lead was phased out of gasoline, blood lead levels dropped dramatically -- even more precipitously than expected, paralleling the decreasing levels in gasoline. Levels that declined further during the 1980s and 1990s continue to fall but at less dramatic rates.
Children between the ages of 1 and 5 with elevated blood lead levels (greater than or equal to 10 micrograms per deciliter (µg/dL)) declined from 4.4% to 2.2% during the 1990s, according the third National Report on Human Exposure to Environmental Chemicals (2003), which reports the NHANES data . In 2000, blood lead levels in the same aged children were measured at 2.23 µg/dL. Still, nearly half a million US children have high enough levels to cause permanent health damage (CDC). Higher levels are seen in urban dwellers, immigrants and refugees.
A main reason for lowering exposure is because lead is a major neurotoxin that can affect childhood development and cause lowered IQs, mental retardation, hyperactivity and stunted growth. As a heavy metal, lead does not break down in the body. What is not excreted is absorbed and settles in bone (90% of adult lead burden), teeth and some tissues, such as the kidneys and liver.
Lead can also affect the immune system. Environmental exposure to lead promotes IgE antibody production in children (Lutz et al. 1999). More IgE can influence stronger asthmatic and allergic reactions. Higher levels of IgE are found in patients with asthma with unknown lead exposure, and in children with or without asthma with elevated lead levels (Joseph et al. 2005).
While lead is no longer used in paint or as a public gasoline additive, it still contaminates drinking water, dust and pollution particles, especially in urban environments (Environmental Health Watch). The CDC defines a dose of lead of 10 micrograms per deciliter of blood (ug/dL) as a level of concern for developmental, behavioral and learning problems. In at least 10 major cities, though, blood lead levels are higher than this standard for 5% or more of tested children (Environmental Health Watch). Minority children have blood lead levels four times higher than those of Caucasians (CDC). While the CDC's 10 ug/dL is a guide for harmful effects from lead, adverse outcomes also occur at lower levels. |
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| A recent recall of toy trains because of lead paint in a hugely popular line of toys reminded parents that lead exposure can come from seemingly innocuous sources. |
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What did they do? Gao et al. collected bone marrow cells from the leg bones of mice and established cell culture conditions that encouraged the development of dendritic cells. The cell cultures were grown for 10 days in solutions that contained 0 (controls), 1, 5 or 25 micromolar (µM) of lead. Lab tests and mouse experiments examined immune response changes associated with lead treatment of the dendritic cells. Responses of exposed and nonexposed cells were compared for differences in quantity, growth, gene expression, signaling, cytokine profiles and other characteristics associated with immune hypersensitivity responses.
What did they find? Lead exposure reduced the number of dendritic cells (DC) produced by the cultured bone marrow cells. However the DCs present were more mature than nonexposed cells. The cytokine profiles were indicative of hypersensitive immune responses.
DCs exposed to lead more effectively stimulated T-cells in animals. When the cells were injected into mice, the lead-exposed DCs produced a more extensive Th2 immune response, which is characteristic of hypersensitivity.
Significant results were found only at the highest lead dose tested of 25 µM.
What does it mean? Lead exposure while dendritic cells (DC) are developing in bone marrow may lead to an enhanced immune response to allergens because the heavy metal changes the way DCs form and respond.
Levels used in these culture experiments are higher (25 µM) than the CDC's intervention level of 10 µg/dL and much higher than the average measured blood level in young children of 2.23 µg/dL. However, millions of US children have much higher blood lead levels due to their environmental exposure to the metal from dust, paint and other sources. Adults exposed to the higher levels through their childhoods harbor more lead in their bodies. Since lead tends to accumulate in teeth and bones, it is likely the DCs that grow in the bone marrow could develop in a lead enriched microenvironment. It is important to note that DCs are constantly being matured in the bone marrow.
Because of the close and essential relationship between dendritic cells and the rest of the immune system, changing the environment surrounding the dendritic cells when they are developing in the bone marrow can alter the general alertness and response of the rest of the immune system.
Lead has been linked to intensified allergic reactions and affects development of certain immune system cells. This is the first report of its effect on the all-important dendritic cells. DCs initiate many kinds of immune responses so altering their behavior could have lasting health consequences.
Eradication of lead from gasoline, solder in tin cans and other products has been very effective at reducing the number of children suffering from lead-induced neurotoxic effects. However, the residual lead in the environment may play a role in other human health issues. The increase in asthma, which is linked to living in developed areas, is one such intersection. The changes described in this paper suggest one way that lead exposure can change the immune system and contribute to allergies and asthma.
Resources:
American Academy of Allergy, Asthma and Immunology.
Centers for Disease Control and Prevention. Asthma.
Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey.
Centers for Disease Control and Prevention. Exposure to lead.
Centers for Disease Control and Prevention. 2003. National Report on Human Exposure to Environmental Chemicals.
Collaborative on Health and the Environment. Asthma: What we know.
Environmental Health Watch. Lead Poisoning.
Environmental Protection Agency. Lead in paint, dust and soil.
Joseph, CLM, S Havstad, DR Ownsby, EL Peterson, M Maliarik, MJ McCabe, Jr., C Barone, and CC Johnson. 2005. Blood lead levels and risk of asthma. Environmental Health Perspectives 113:900-904.
Lutz, PM, TJ Wilson, AL Jones, JS Gorman, NL Gale, JC Johnson and JE Hewett. 1999. Elevated immunoglobulin E (IgE) levels with exposure to environmental lead. Toxicology 134:63-78.
Mannino DM, DM Homa, LJ Akinbami, JE Moorman, C Gwynn, and SC Redd. 2002. Surveillance for asthma -- United States, 1980-1999. MMWR Surveillience Summary 51(1):1-13.
Wikipedia. Dendritic cells.
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