Pollution's Immune Response Trigger: What You Need To Know

Air pollution is a worldwide problem that poses a challenge to human health, as well as to animals and plants. The immune system is sensitive to any environmental changes, and its functioning is vital for a healthy body.

The effects of air pollution on the immune system have been widely studied, and it has been found that air pollution can trigger immune responses and cause diseases. Air pollution can enhance T helper 2 (Th2) and T helper 17 (Th17) adaptive immune responses, as seen in allergy and asthma, and dysregulate anti-viral immune responses. Pollutants trigger inflammatory cytokine release from the epithelium and macrophages.

In addition to the respiratory system, air pollution also affects the skin and the nervous system. It can cause skin ageing, allergic contact dermatitis, atopic dermatitis, psoriasis, acne, and skin cancer. Air pollution exposure starts in utero and can cause delayed chronic diseases later in life.

The clinical effects of air pollution vary based on the type of pollutant, but generally include an increased risk of respiratory illness, cardiovascular problems, skin diseases, cancer, global warming, and acid rain.

Strategies such as vitamin D supplementation, adequate sleep, and a balanced and healthy diet can help to ameliorate the harmful effects of air pollution on the immune system.

Air pollution can trigger the release of inflammatory cytokines from the epithelium and macrophages

Air pollution is one of the greatest environmental risks to health, and it impacts the lungs' innate and adaptive defense systems. A major pollutant in the air is particulate matter (PM), a complex component composed of elemental carbon and heavy metals. According to the World Health Organization, 99% of people live in areas where air quality levels are lower than the recommended guidelines. This suggests that the effect of air pollution exposure on asthma is a crucial health issue worldwide.

Macrophages are essential in recognizing and processing any inhaled foreign material, such as PM. Alveolar macrophages are one of the predominant cell types that process and remove inhaled PM by secreting proinflammatory mediators from the lung.

The respiratory epithelium constitutes an active part of the immune system. It responds to environmental stimuli and secretes mediators, causes damage to the mucosa, and leads to a reduction in mucociliary clearance. Once activated, the inflammatory cells reach the lung tissue, enhance local inflammation, and influence the increased production of mediators by both epithelial cells and the endothelial cells of the airways.

The effects of air pollution on the immune system are notably diverse, and immunological research does suggest potential strategies to ameliorate such effects, for example, with vitamin D supplementation.

Pollutants can enhance T helper 2 and T helper 17 adaptive immune responses

T helper 2 (Th2) cells are a subset of T helper cells that secrete cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13. These cytokines are important in the immune response to extracellular pathogens, such as helminth infections. Th2 cells are also involved in the development of atopic diseases such as asthma.

T helper 17 (Th17) cells are another subset of T helper cells that produce cytokines such as interleukin-17 (IL-17), IL-21, and IL-22. Th17 cells play a crucial role in host defence against extracellular bacterial infections and are involved in the pathogenesis of many autoimmune diseases.

Pollutants can enhance the adaptive immune response by promoting the differentiation of naïve CD4+ T cells into Th2 and Th17 cells. This can lead to an imbalance in the immune system, resulting in allergic and autoimmune diseases.

For example, exposure to diesel exhaust particles (DEP) has been shown to enhance the production of IgE antibodies and skew the immune response towards a Th2-type cytokine pattern. DEP can also induce the production of IL-4, a key cytokine in the differentiation of naïve CD4+ T cells into Th2 cells and the production of IgE antibodies.

In addition, pollutants such as DEP can act as adjuvants, enhancing the allergic response to allergens. DEP can bind to pollen grains and act as a carrier, transporting allergens into the airway. DEP can also induce the production of IL-4, which promotes the differentiation of naïve CD4+ T cells into Th2 cells and the production of IgE antibodies.

Overall, pollutants can enhance T helper 2 and T helper 17 adaptive immune responses by promoting the differentiation of naïve CD4+ T cells into these subsets and by acting as adjuvants to enhance the allergic response.

Air pollution can dysregulate anti-viral immune responses

The primary site of exposure to air pollution is the respiratory tract following inhalation. The respiratory tract, from nasal passages down through the airways to alveolar gas exchange units in the lungs, represents the prime interface between the immune system and the airborne environment. Inhaled particulates and gases interact with epithelial cells lining the airways and professional immune cells within the airways. These cells sense and can be ‘stimulated’ by air pollution as pollution constituents trigger cellular signalling pathways. Stimulated cells act as part of multicellular immune responses, and perturbation of these can cause disease.

Air pollution can generate free-radical oxidants (reactive oxygen species) in both cellular and acellular experimental systems, and ambient particulate matter is well known to cause oxidative stress and reduction of endogenous antioxidants. The induction of oxidative stress by PM is thought to be caused by both the heavy metal and organic compound components of PM. Organic compounds present in PM, or formed by cellular metabolism of PM, can donate electrons to O2 molecules to form superoxide free-radicals. Transition metals can similarly donate electrons to form superoxide and hydrogen peroxide, and can directly deplete endogenous thiol antioxidants. Oxidative stress can induce NFκB and AP-1 signalling, as well as transcription of genes containing the antioxidant-responsive element (ARE) promoter , however the exact mechanisms are not fully elucidated.

TLRs are a type of cellular receptor designed to sense pathogen-associated molecular patterns (PAMPs) of potentially infectious micro-organisms and also other similar noxious stimuli, and it is notable that pollution can trigger these receptors. The ability of urban PM to stimulate cells through TLRs is thought to be due to the particles containing microbial molecules such as lipopolysaccharide (LPS) and fungal spores, that are natural ligands for TLRs, and also particles inducing production of host-derived molecules that can act as alternative agonists for TLRs, such as oxidised phospholipids and nucleic acids (from cellular damage).

The aryl hydrocarbon receptor (AhR) is a cytosolic environmentally sensing receptor, first discovered as a ligand for dioxin and extensively reviewed by Stockinger et al. Binding of PAH ligands triggers nuclear translocation and induction of xenobiotic-metabolising enzymes such as CYP1A1 and CYP1B1 and these, in turn, produce more cytotoxic/genotoxic products. The toxicity of PAHs is supported by research from den Hartigh et al. in which they have shown that addition of an AhR antagonist, a-naphthoflavone, to monocyte cultures can decrease PM-stimulated TNFα, indicating that this PM-stimulated pro-inflammatory cytokine release is somewhat regulated by AhR signalling.

Air pollution can directly trigger cellular signalling pathways, and both cell culture studies and animal models have shown profound effects of air pollutants on every type of immune cell studied. In addition to the general pro-inflammatory nature of these effects, many of these studies suggest an action of air pollution to augment Th2 immune responses and perturb anti-microbial immune responses. Consistent with these mechanistic immunological actions, elevated air pollution is associated with respiratory exacerbations.

Air pollution can cause oxidative stress, which can lead to DNA damage and cell death

Air pollution is a complex mixture of particulate matter and gases that are produced by multiple industrial, commercial, and individual activities. It is well known to be harmful to health, contributing to the development of cardiovascular disease, metabolic disorders, and a number of lung pathologies, including asthma and chronic obstructive pulmonary disease (COPD).

One of the mechanisms involved in the health effects of air pollution is oxidative stress, which can be induced by direct oxidative effects of ozone or the induction of reactive oxygen species (ROS) following particulate matter exposure. Oxidative stress activates downstream inflammatory pathways, such as mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and activator protein 1 (AP1), leading to increased cytokine expression, activation of immune cells, and ultimately inflammation.

Oxidative stress can also cause DNA damage, which is a prerequisite for most mutations and cancer. Studies have shown that exposure to air pollution particles is associated with elevated levels of oxidatively damaged nucleobases in circulating blood cells and urine from humans. This is supported by observations of elevated levels of genotoxicity in cultured cells exposed to similar particulate matter.

In addition, air pollution can affect the immune system and has been linked to an increased risk of allergies and autoimmune disorders. Certain pollutants, such as diesel exhaust particles, can act as adjuvants and enhance immunoglobulin production, skewing the immune response towards a Th2-type pattern, which is associated with allergic inflammation.

The effects of air pollution on the immune system are complex and can vary depending on individual factors such as genetic background, diet, and smoking habits. However, overall, air pollution has been shown to have detrimental effects on immune function and health.

Air pollution can have adverse effects on the skin, such as allergic contact dermatitis, atopic dermatitis, and acne

Allergic Contact Dermatitis

Allergic contact dermatitis is an inflammatory skin disease in which patients have underlying skin barrier defects and a heightened immune response to irritants and allergens. Air pollution can trigger this condition by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, impairing the skin barrier, and initiating a proinflammatory response.

Atopic Dermatitis

Atopic dermatitis is a common, heterogenous, chronic‐intermittent, eczematous skin disorder that starts at infancy or early childhood and persists for a large part of life. It is characterized by frequent relapse with intense pruritus that deteriorates the quality of life and decreases treatment satisfaction of afflicted patients. The increasing prevalence of atopic dermatitis parallels a global rise in industrialization, urban living, and increasing air pollution over recent decades.

Acne

Acne is influenced by air pollution. The prevalence of acne is similar between Asian and Caucasian women, but Asian women were reported to have a higher prevalence of inflammatory than comedonal acne. In addition, Asian women also report that their symptoms are exacerbated during periods of high air pollution.

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