Nutrition and the immune system

Synthesis of S- and N-arylpiperazinylalkyl derivatives of ethyl 2-thio-4-oxo-3,4-dihydro- and 2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-5-carboxylate is described. Some of the obtained compounds are pharmacologically active.     

Nutrition and the immune system: an introduction

Nutrition is a critical determinant of immune responses and malnutrition the most common cause of immunodeficiency worldwide. Protein-energy malnutrition is associated with a significant impairment of cell-mediated immunity, phagocyte function, complement system, secretory immunoglobulin A antibody concentrations, and cytokine production. Deficiency of single nutrients also results in altered immune responses: this is observed even when the deficiency state is relatively mild. Of the micronutrients, zinc; selenium; iron; copper; vitamins A, C, E, and B-6; and folic acid have important influences on immune responses. Overnutrition and obesity also reduce immunity. Low-birth-weight infants have a prolonged impairment of cell-mediated immunity that can be partly restored by providing extra amounts of dietary zinc. In the elderly, impaired immunity can be enhanced by modest amounts of a combination of micronutrients. These findings have considerable practical and public health significance.     

Intervention in autoimmune diabetes by targeting the gut immune system

BB rats and nonobese diabetic (NOD) mice spontaneously develop autoimmune insulin dependent diabetes and serve as models for human type I diabetes. During progression of the disease the cytokine pattern elaborated by islet infiltrating immune cells shifts from a Th2 or Th0 toward Th1 type. Only the latter is associated with "destructive" insulitis. We discuss here attempts to modulate disease progression by targeting the gut immune system with bacterial immunostimulants. Oral dosing of diabetes prone BB rats with lipopolysaccharide (LPS) or the Escherichia coli extract OM-89 lead to a Th2-shift of pancreatic mRNA expression. In vitro studies showed that repeated exposure toward LPS or OM-89 lead to downregulation of proinflammatory macrophage responses. In the NOD mouse, repeated oral dosing of OM-89 caused a Th2 shift in the gut cytokine gene expression, probably because of desensitization of macrophages and other antigen presenting cells. Concomitantly, diabetes prevention by oral insulin was improved. In conclusion, oral dosing with bacterial immunostimulants dampens Th1 type immune reactivities of the gut immune system and thereby promotes oral tolerance mechanisms. Downregulation of proinflammatory immune reactivities by repeated exposure to bacterial stimulants requires intact desensitization mechanisms in macrophages or other antigen presenting cells.     

Role of NF-kappaB in immune and inflammatory responses in the gut

BACKGROUND: Liver disease in chronic hepatitis C virus (HCV) infection ranges from minimal lesions to liver cirrhosis, eventually evolving to hepatocellular carcinoma. Whether and how HCV determines the different clinical and histological manifestations of the disease is not fully understood. AIMS: To verify whether the amount of virus in individual patients could be related to the severity of liver injury. PATIENTS AND METHODS: Levels of HCV RNA were measured in serum in 96 consecutive patients with chronic hepatitis type C using a signal amplification assay. The relation between viraemic values and the corresponding viral load in the liver was assessed in a subgroup of 21 patients in whom HCV RNA was measured in serum samples and liver specimens obtained at the same time. RESULTS: A positive correlation was observed between the amount of viral nucleic acid in the two compartments, indicating that levels of viraemia reflect the amount of virus present in the liver. Viral load did not correlate with aminotransferase activities nor with histological diagnosis, and serum and liver levels of HCV RNA were not significantly different in patients infected by the various HCV genotypes. CONCLUSIONS: Measurement of HCV replication in serum is a mirror of viral replication in the liver. The extent of replicative activity of HCV does not seem to play a role in the modulation of the associated hepatic disease.     

Sports and the immune system

Acute exercise is followed by a mobilization of white blood cells, mainly induced by increased levels of catecholamines and cortisol. NK-cells react the most intensive, they can increase fivefold after intensive exercise. Additionally a weak acute-phase reaction occurs. Most of these changes normalize during twenty-four hours. Parameters of the humoral immune system may be different from the pre-exercise levels up to seventy-two hours. Repeated physical exercise, which is typical for sports, is followed only by small changes of immunologic parameters under conditions of rest. Epidemiological studies give clues that the rate of upper respiratory tract infections in athletes can be described by a j-shaped curve. Moderately active subjects have the lowest rate of infection. For this influence of exercise on health mainly functional changes seem to be important. Especially after excentric exercise immunological cells can be seen in the muscle tissue, which remove destructed tissue. Not very much is known about the role of the immune system in the regeneration of tendons and other bradytrophic tissues.     

Ozone and the immune system

This review focuses on the effect on health of changes in the immune system secondary to ozone exposure and on various mechanistic hypotheses put forward. Beyond the problems related to the variability of study criteria (e.g. age, sex, concentration and duration of different types of exposure, the slightly volatile nature of ozone and the complexity of the immune system), ozone may induce immunostimulation as shown by intensified allergic phenomena or immunosuppression expressed by increased sensitivity to bacterial infections. Different functions of the immune response (for example macrophage and polynuclear phagocytic and bactericidal activity, NK activity, cytokine and antibody production ...) are affected. In terms of risk, the consequences of these changes depend on their intensity, their perennial nature and their association with particular genetic characteristics or other forms of external aggression, for example infection. The effect of exposure to a mixture of pollutants with unknown interactions should also be taken into consideration. Finally, the problem of normal but possibly exaggerated immune response to a compound whose allergenicity may have been modified by ozone must also be taken into account.     

Interaction of the epiphysis and the immune system

First indications that the pineal gland may be involved in endocrine immunomodulation came from early reports on anti-tumor effects of pineal extracts in animals and humans. In the meantime, evidence has accumulated suggesting that melatonin, the major endocrine product of the pineal gland-as a well preserved molecule during evolution-is indeed involved in the feedback between neuroendocrine and immune functions. At present we are beginning to understand the mechanisms of action by which melatonin affects cellular functions, and from the variety of possible direct and indirect interactions it appears that melatonin may play a complex physiological role in neuroimmunomodulation. In this article we present a critical review of the numerous reports on the influence of melatonin on immune functions and discuss the possible underlying molecular pathways. In addition, a short comment is given on the current public discussion as to the clinical value of melatonin.     

Female sex hormones and the immune system

Generally, females have a more active immune response and a concomitantly higher incidence of autoimmune diseases as compared to males. Growing evidence has shown that female sex hormones play a major role in this heightened immune response. However, despite extensive studies, the mechanisms of female sex hormones are not precisely understood. Earlier evidence suggest that female sex hormones acted via the thymus gland. In recent years it has become apparent that female sex hormones have distinct effects on the function of T cells, B cells, or mononuclear phagocytes. The presence of sex hormone receptors on the immune cells indicates the effects of female sex hormones on these cells are mediated by these receptors. The effects of female sex hormones on the immune system and the possible mechanisms are discussed in this review. Female sex hormone modulation of immune responses provides a basis for understanding gender-related differences in certain autoimmune and neoplastic disorders.     

Enteric nervous system and endocrine cells demonstrated in the gut in teratomas

A case of retroperitoneal teratoma, showing considerable morphological development presented as an encapsulated and pedunculated tumour with a seemingly mature intestinal loop. Markedly complex intramural nerve plexuses and numerous epithelial endocrine cells were revealed immunohistochemically in the gut tissue. Ten other mature teratomas containing gastrointestinal tissues were examined for comparison, but neither intramural ganglia nor nervous networks were found in the gut components, despite the presence of amine- and/or peptide-containing endocrine cells in all intestinal mucosa linings. Enteric endocrine cells were found to occur irrespective of the differentiation of intestinal layers or the occurrence of neural elements. These findings suggest that the epithelial endocrine cells of intestinal mucosa do not have the same origin as enteric neurons, but are rather of endodermal origin. This invertebrate well-formed teratoma, containing a highly organized enteric nervous system, suggests that teratoma and fetus in fetus are related entities distinguished by the presence of a vertebral axis.     

Changes in the aging immune system

We describe a solid-state, silicon integrated, bidirectional flow sensor for respiratory applications. The sensor is a thermal vector sensor. The electronic circuitry for obtaining bidirectional sensitivity is presented together with actual application to a healthy volunteer put on mechanical ventilation. The sensor's input flow range is from -60 to +60 L/min, and its rise-time is < or = 40 ms and fall-time is < or = 60 ms. The effect of changes in gas composition as used in mechanically ventilated patients on the sensor output signal are estimated to be less than 2%. The temperature sensitivity is about -1.5% per degree Celsius.     

Cell adhesion in the immune system

Cell adhesion molecules have an important role to play in many facets of the immune system. At a recent meeting their role in leukocyte migration, inflammation, cancer metastasis and lymphocyte development was discussed.     

Nutrition in the pathogenesis, therapy and prevention of digestive system diseases

The role of nutrition in the pathogenesis, therapy, and prevention of gastrointestinal diseases is discussed. Although nutrition is not a leading cause of most gastrointestinal diseases, the role of nutrition in their pathogenesis is very great. Nutritional monitoring of the Russian Federation's population has revealed a shortage of many essential nutrients to be consumed, which may result in worsening of various gastrointestinal diseases. The most promising way of solving this problem is to supplement their diets with biologically active additives (Nutricevtics) which may be a main source of essential nutrients, such as vitamins B, beta-carotene and omega 3-polyunsaturated fatty acids.     

The autonomic nervous system and the immune system in juvenile rheumatoid arthritis

CD16, the low affinity receptor for monomeric IgG (Fc gamma RIIIA), is a well characterized activation molecule on NK cells. In this study we investigated the role of CD16 in NK cell-mediated regulation of immunoglobulin production. Cocultures of the CD16+ human NK clone CNK6 and highly purified SAC/IL-2-activated B lymphocytes with various CD16 antibodies showed significantly diminished NK-enhanced immunoglobulin production in a dose-dependent manner, indicating that CD16 is relevant in NK-B cell interaction. Similarly, recombinant soluble CD16 incubated with B cells before cultures, suppressed the NK cell-stimulated B cell antibody response. Enhanced immunoglobulin production was also inhibited by Fc-specific F(ab')2 anti-body fragments. Coculture of NK cells with B lymphocytes resulted in induction of mRNA for IFN-gamma and TNF-alpha. The accumulation of mRNA for these cytokines was prevented by addition of CD16 and Fc-specific antibodies. It is proposed that interaction of CD16 on NK cells with B cell bound immunoglobulin leads to induction of cytokines in NK cells which stimulate immunoglobulin production by B cells.