The TH2Bias of the Neonatal Immune System

Before the fetus has even a rudimentary immune system, the maternal immune response has had to adapt to permit development of a child whose paternal antigens are cause for immune rejection. Evidence exists in both murine and human studies that during pregnancy, TH2 immune responses dominate in the mother, reducing TH1 type reactions that would presumably mediate rejection of the fetus (reviewed in Donovan and Finn 1999 Warner and Warner 2000). In support of this idea, Sills and coworkers...

Fetal IgE

Although T cells act as a driving force in the asthmatic response, the IgE-mast cell interaction is a central component, as it is for all immediate-type hypersensitivity responses. Therefore, understanding the production of IgE in the fetus provides a key for not only elucidating asthma development in children, but also in exploring the maternal influence on fetal and neonatal sensitization to allergens. Several studies indicate that increased cord blood levels of IgE are associated with an...

Sensitization vs Triggering

Encountering any particular antigen (Ag) for the first time sensitizes, or primes, a developed immune system. This elicits a primary T cell response characterized by a relatively slow clonal expansion of antigen-specific T cells secreting a variety of cytokines of no particular biological focus. Sensitization of T cells also allows the immune system to react with a memory, or anamnestic, response upon a second exposure and all subsequent exposures to the same antigen. A memory T cell response...

Nicotine

Cholinergic input plays a critical role in brain development, and nicotine, a cholinergic agonist, can disrupt this normal development (Roy et al. 2002). Interference with this input (excessive or inappropriately timed) can have broad-ranging results both in the brain and the peripheral nervous system. Activation of cholinergic input by nicotine is suspected to cause many of the adverse effects of maternal smoking. This is particularly important since the fetus accumulates relatively high...

Effects of ETS on Respiratory Health

There exists a significant body of research on the potential effects on respiratory health from exposure to environmental (passive) tobacco smoke (ETS) (reviewed in National Academy of Sciences 2000). Many components of ETS are known lung irritants. There have been direct associations shown between exposure to tobacco smoke and the development of lung cancer, obstructive airway disease, chronic bronchitis, ear infections, and asthma. It is small wonder that ETS is associated with so many...

Development Of The Newborn Immune System

Upon parturition, the immune system of the neonate becomes abruptly released from the immunosuppressive intrauterine environment (Holt 2003 Janeway Jr. et al. 1997b West 2002) and is concomitantly exposed to a world of antigens. Unlike the situation in rodents, the human neonatal immune system has achieved a significant level of maturity (Holt and Jones 2000 Peakman et al. 1992 West 2002). However, in comparison with the human adult immune system and with respect to the antigenic challenges...

Heavy Metals

The immunotoxic effects of heavy metals, such as lead, arsenic, and mercury exposure are well recognized (Bernier et al. 1995 Schuppe et al. 1998). In comparison to most environmental toxicants, the mechanism of metal immunotoxicity is well studied (reviewed in Schuppe et al. 1998). It is currently believed that metals initially elicit a cell-mediated immune response by binding to MHC class II molecules or MHC-bound self-peptides. The metal-MHC complex is then recognized by CD4+ T cells....

Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are a group of unsaturated cyclic hydrocarbons containing two or more rings, derived from the incomplete burning of organic materials. They are common environmental contaminants produced by diverse industrial (Ball and Dawson 1969 Ball et al. 1966 Gricuite 1979) and domestic (Huhti 1981 Aggarwal et al. 1982 Grimmer and Pott 1983) processes. Contamination and exposure to PAHs can occur in industrial, rural, and urban settings, as PAHs can be found in...

Common Effects of TCDD and CsA on T Cell Development

The developing immune system has been demonstrated to have a high sensitivity to TCDD. This, coupled with evidence that increased autoimmune disease may result following TCDD exposure in adult animals, has raised questions regarding possible relationships between prenatal exposure to TCDD and increased postnatal autoim-munity. Low-level maternal TCDD exposure results in atrophy of the developing thymus as well as inhibition of thymocyte differentiation (Table 13.2). T-progenitor cells from the...

Manipulators Of The Developing Immune System

The immune system matures according to developmental pathways but also in response to the environment. Four manipulators impact many facets of the immune system and deserve attention. First and foremost, nutrition plays a vital role in the ability of the body to defend against pathogens (Bardare et al. 1993 Devereux et al. 2002). The majority of immunocompromised individuals in the world simply lack nourishment (Janeway Jr. et al. 1997a). Studies implicate maternal diet in development of atopic...

Pyrethroid Insecticides Cypermethrin

Cypermethrin is a widely used synthetic type II pyrethroid insecticide due to its high insect toxicity, low mammalian toxicity, and rapid metabolism (Crawford et al. 1981 Rhodes et al. 1984). Cypermethrin is primarily considered to be a sodium channel toxin. At high concentrations, pyrethroids induce a long-lasting depolarization and block nerve conduction. However, other secondary mechanisms of action are also involved in their toxicity, including antagonism of GABA inhibitory action,...

Alcohol

A number of studies have shown that consumption of alcohol inhibits immune function in both adult humans and animals (Jerrells et al. 1986). In adults, ethanol is immunosuppressive, decreasing both the cellularity of the thymus and spleen and interfering directly with B and T-lymphocyte responses. Additionally, alcohol suppresses the phagocytic activity of macrophages and reduces NK cell activity (Seelig et al. 1996). Ethanol consumption alters cytokine production, including IL-2, IL-5, IL-6,...

Current Assessment Of The Immune System In Epa Guideline Studies

A number of guideline toxicity studies utilized in the regulation of pesticides, industrial chemicals, and environmental pollutants include assessments of immune system structure and or function. The majority of these studies are performed in adult animals. Although they were not developed to assess the developing immune system, they can provide valuable information that could indicate the necessity for further testing to evaluate effects on the immune system following developmental exposure....

Signaling Pathways and Transcription Factors Involved in Asthma Pathogenesis

Soluble mediators may play important roles in the sensitization and triggering of asthmatic responses, but they only do so by acting through specific receptors. Binding to a specific receptor by any cognate ligand normally transduces a signal to the nucleus to transcribe, or block the transcription of, a gene or genes via one or more intracellular biochemical pathways. Steps along a pathway are referred to as pathway intermediates, and those intermediates directly responsible for binding to DNA...

Asthmatic Inflammation

Trimeric Fceri Eosinophils

Asthma is a chronic inflammatory disease of the airways. Asthmatic inflammation involves complex interactions between the cytokines and signaling pathways of many cell types. In adults and children, T cells are known to be integrally involved in this process (Azzawi et al. 1990 Corrigan and Kay 1990 Wardlaw et al. 1988). The maintenance of airway inflammation is attributed, in adults, to chronically activated memory T cells sensitized against a variety of allergens (Corrigan and Kay 1990) and,...

Therapeutic Immunosuppressant Levels In Mammary Gland Secretions

Many of the immunosuppressive drugs used during pregnancy are also found in breast milk. Currently, the American Academy of Pediatrics AAP provides guidelines for breastfeeding based on the excretion rate and potential teratogenic effects of each drug Tendron et al. 2002 . For example, limited concentrations lt 10 of prednisone and prednisolone have been measured in breast milk, levels perceived by the AAP as nonthreatening to the breastfed infant Coulam et al. 1982 Ost et al. 1985 . Thus,...

Timing Of Immune Assays For Detecting Developmental Immunotoxicity

Development of the immune system has been more studied and better defined in the mouse than any other species see Chapter 1 . With this in mind, many immune function tests utilized in adult mouse models are not valid in perinatal mice simply because of the immaturity of their immune systems. Therefore, an adult mouse immunotoxicity risk assessment screening battery must be modified to be age-appropriate, if it is to be used for detecting postnatal immune deficits following prenatal chemical...

The Pigs Intestinal Immune System During Postnatal Development

The early postnatal development of the gut immune system is important for effective immunological responses towards nutritional and microbial antigens in the intestinal lumen. Adaptation to the commensal flora, defense against pathogens, and the development of oral tolerance to food components are essential immunological processes. Depending on the food composition and on the presence of oral food components, the morphology of both the intestinal mucosa and the intestinal immune cells changes...

Diazepam Valium

Diazepam DZP is a benzodiazepine BDZ with central nervous system CNS -depressant properties. It has anxiolytic, sedative hypnotic, muscle relaxant, and anticonvulsant effects. DZP is used in humans for the short-term relief of symptoms related to anxiety disorders the treatment of agitation, tremors, delirium, seizures, and hallucinations as a result of alcohol withdrawal the relief of muscle spasms in certain neurological diseases and the control of active seizures Costa and Guidotti 1979 ....

Postnatal Immune System

Continued maturation of the macaque immune system has been provided by evaluation of various serum parameters during the postnatal period. Longitudinal measurements of CD4 CD8 T cell ratios have been reported in colony-bred rhesus Dykhuizen et al. 2000 and cynomolgus Bleavins et al. 1993 Baroncelli et al. 1997 macaques using flow cytometry. In both macaques, the CD4 CD8 ratios slowly decline with age, predominantly due to decreasing CD4 T cell counts Table 7.7 . The CD4 CD8 values between 6...

Proposed Content Of A Developmental Immunotoxicity Study

Although the need for developmental immunotoxicity testing has long been recognized by the scientific and regulatory communities NRC 1993b USEPA 1999, 2002b , there is currently no formal EPA testing guideline protocol for this study. Studies have, however, been conducted in numerous laboratories to assess the developmental immunotoxic potential for a myriad of pharmaceuticals, pesticides, and environmental pollutants. Additionally, the National Toxicology Program NTP has devised an...