抗原口服耐受性影响因素的研究进展

抗原口服耐受性是经口接触某种抗原物质后机体再次接触这种抗原时对其免疫应答的主动抑制.机体每天都要接触大量的食物抗原,而抗原口服耐受性的存在使绝大部分人不会对这些抗原产生过敏反应.食物致敏性是人们关注的热点之一,通过建立动物模型来研究食物致敏性是一条比较直接的途径,而降低实验动物的口服耐受性可有效提高该模型的检出效力.本文就近年来口服耐受性影响因素及消除口服耐受性的措施或方法方面的研究进展进行综述.     

Regulation of Dendritic Cell Function by Dietary Polyphenols

Marked changes in socioeconomic status, cultural traditions, population growth, and agriculture have been affecting diets worldwide. Nutrition is known to play a pivotal role in the pathogenesis of several chronic diseases, and the use of bioactive food compounds at pharmacologic doses is emerging as a preventive and/or therapeutic approach to target metabolic dysregulations occurring in aging, obesity-related chronic diseases, and cancer. Only recently have data on the effects of specific nutrients or food on the immune system become available, and studies regarding the human immune system are still in their infancy. Beyond providing essential nutrients, diet can actively influence the immune system. Understanding how diet and nutritional status influence the innate and adaptive arms of our immune system represents an area of scientific need, opportunity, and challenge. The insights gleaned should help to address several pressing global health problems. Recently, biologically active polyphenols, which are widespread constituents of fruit and vegetables, have gained importance as complex regulators of various cellular processes, critically involved in the maintenance of body homeostasis. This review outlines the potential effects of polyphenols on the function of dendritic cells (DCs), key players in the orchestration of the immune response. Their effects on different aspects of DC biology including differentiation, maturation, and DC capacity to shift immune response toward tolerance or immune activation will be outlined.     

Food allergy

Adverse clinical reactions to food associated with disturbed immunologic function (food allergy) affect 1-3% of the population and vary from life-threatening to a minor inconvenience. They must be differentiated from reactions caused by toxins, pharmacologic agents, enzyme deficiences and non-specific release of inflammatory mediator substances. Enteric absorption of food protein antigens which may occur despite an array of gastrointestinal protective mechanisms normally induces both a protective immune response and immunologic tolerance. Quantitative changes in absorption related to deficient protective mechanisms or excessive antigen load may contribute to the development of an allergic immune response and explain the greater incidence of food allergy in infants and children. Important factors include immunologic immaturity, enhanced macromolecular mucosal transport, intrauterine and neonatal malnutrition, breast feeding and infection. Double-blind food challenge tests remain as the most definitive diagnostic yardstick but carefully standardized skin tests may be helpful if interpreted in the context of the clinical history. Despite the association of food allergy with food antigen specific IgE hypersensitivity, immune complex formation and lymphocyte sensitization the pathophysiological changes which result in symptoms remain obscure. Recent advances have clarified many aspects of our knowledge of food allergy but inevitably have raised many more questions for future study.     

免疫耐受在牛乳过敏中的研究进展

食物过敏是机体对过敏原产生的一种不良免疫反应,而免疫耐受是指机体对摄入的食物抗原不产生此类免疫应答.近年来,牛乳过敏的发生率越来越高,大部分牛乳过敏的儿童3岁之后出现了免疫耐受.基于此,介绍了牛乳过敏及引发免疫耐受的相关免疫细胞包括树突状细胞、调节性B细胞、调节性T细胞在免疫耐受中的作用及3种诱导免疫耐受的方法.     

Immune modulation in suckling rat pups by a growth factor extract derived from milk whey

Oral tolerance to foreign enteral antigens is not fully developed in early neonatal life. Epidemiological evidence supports a role for maternal milk in the development of immune responses, including oral tolerance. Formula fed infants have an increased susceptibility to food allergy and the later development of autoimmune disease. This may relate to the lack in infant formula of growth factors found in maternal milk. Bovine milk contains proteins, growth factors and cytokines. Various studies have outlined the immune modulating potential of bovine milk-derived products. Fractionated whey extracts have therapeutic potential in disease states where there is an excessive inflammatory reaction, and disease preventive potential for infants who are not breast-fed. We have shown that daily oral administration of a growth factor-enriched fraction from milk whey to naturally suckling rat pups between days 4-9 postnatal can down-regulate immune activation to a specific orally administered food antigen, ovalbumin, assessed by lymphocyte proliferation. In addition, non-specific down-regulation in the intestine was observed as assessed by the expression of MHC I. Treatment of rat pups with whey extract at the time of oral sensitisation to ovalbumin also resulted in an increased secretion of TGF-beta into the culture supernatant of spleen cells incubated with specific antigen. TGF-beta is an immuno-down-regulatory cytokine involved in tolerance induction. Immune modulation by extracts derived from milk whey could be of potential benefit for formula-fed and pre-term infants in reducing susceptibility to inappropriate activation to food antigens.     

乳酸菌作为粘膜重组疫苗呈递载体的研究进展

乳酸菌是对人和动物具有多种益生功能的食品级微生物,被广泛地应用于食品、医药、生物技术等领域。乳酸菌的安全益生特性及乳酸菌基因表达系统研究取得的重大进展,使得重组乳酸菌黏膜疫苗成为研究的热点。乳酸菌作为黏膜免疫的蛋白呈递载体,可诱导机体产生有效的免疫反应和免疫耐受,具有巨大的发展潜力。     

Assessment of Slovak population exposure to cadmium from food

Exposure of the Slovak Republic population to cadmium from food and drinks was studied. Calculations were done by means of 1,66,312 food, plant and animal raw materials and drinks sampled within systematic inspection and monitoring of contaminants in 1990–2003. Exposure assessment of average inhabitants to cadmium from actual and model consumption patterns were calculated and compared with the provisional tolerable weekly intake (PTWI) value. Considering the model consumption, the exposure doses were assessed also for selected demographic groups. The assessed exposure of the population to cadmium has been persistently low with a moderately decreasing tendency especially for the past few years. The assessed real weekly exposure doses of cadmium from foodstuffs and beverages in the last 5 years while using the mean values and median values were 20–14.8% PTWI and 12.6–7.6% PTWI, respectively.     

Satiety Effects of Lentils in a Calorie Matched Fruit Smoothie

The food environment is changing, with consumers being more health conscious and concerned about the wholesomeness of their food than ever before. Consumers are looking for nutritious whole food alternatives to fill their plates and stomachs. Pulse grains, rich in both protein and fiber, may be the ideal candidate to promote satiety at meals. In a crossover feeding study, participants consumed calorie‐matched fruit smoothies prepared with either an ice cream base or pureed red lentils. Self‐reported satiety, blood glucose response, and ad libitum food intake at a secondary meal were all measured along with breath hydrogen and methane and gastrointestinal tolerance. While there was no significant difference in satiety response or energy intake at the secondary meal, the nutrient profile of the lentil smoothie was improved with increased protein and fiber and dramatically lower fat content. Blood glucose response was not statistically different between the 2 treatments. Both smoothies were generally well tolerated; however, there was a slightly elevated AUC for perceived gastrointestinal tolerance over 24 h in the lentil smoothie. No difference in breath hydrogen or methane response was seen between treatments. The substitution of lentils into a meal is not likely to improve satiety; however lentils are a good source of fiber and protein and can greatly improve nutritional content of the meal.     

Impact of dietary factors and food processing on food allergy

Allergic reactions to food can significantly reduce the quality of life and even result in life‐threatening complications. In addition, the prevalence of food allergy has increased in the last decades in industrialized countries and the mechanisms underlying (increased) sensitization are still not fully understood. It is believed that the development and maintenance of oral tolerance to food antigens is a process actively mediated by the immune system and that this reaction is essential to inhibit sensitization. Ongoing research indicates that different dietary factors also may contribute to immune homeostasis and oral tolerance to food and that food processing modulates allergenicity. One of the major questions in food allergy research is therefore which impact nutrition and food processing may have on allergenicity of food and perhaps on sensitization. We summarize in this review the different dietary factors that are believed to contribute to induction of oral tolerance and discuss the underlying mechanisms. In addition, the functional consequences of allergen modification will be emphasized in the second part as severity of allergic reactions and perhaps sensitization to food is influenced by structural modifications of food allergens.     

食物致敏原表位定位技术的研究进展

食物致敏原是引起食物过敏的元凶，多为蛋白质。抗原表位是在抗原分子中与抗体反应或被抗原受体识别，并引发机体免疫应答的特殊化学基团。从表位水平认识食物致敏原，能揭示食物过敏的物质基础，为解决食物过敏问题提供精准的靶标。本文基于表位结构和定位方法的不同，介绍了食物致敏原表位定位技术的发展，并进一步展望了致敏原表位信息对于改进食物过敏鉴定技术和低致敏食物加工方法的应用前景。     

The use of gnotobiological models for the studies of immune mechanisms

Germfree (GF) animals are widely used for discrimination of natural mechanisms (genetically determined) from adaptive mechanisms of immunity induced by external antigens. GF rats fed at least for first 5 days after birth with artificial diet LNa, deficient in unsaturated fatty acids, were in contrast to those fed with K 50 diet deeply suppressed in humoral and cellular immune reactivities during their life. GF piglets, deprived from maternal colostrum (CF) as a source of passively transferred maternal antibody, immunized with preformed Ag/Ab complexes (HSA anti HSA) responded according to the composition of complexes (Ab excess, equivalence, Ag excess) by low or high dose tolerance or by secondary response. Similar pictures of response were obtained in groups of presensitized GF-CF piglets by immunization with different doses of antigen. It is concluded that 3 different types of response are the result of Ag/Ab complexes acting or formed on the lymphocyte membrane and exerting stimulatory or down-regulatory signals.     

Considerations on Developing Criteria to Determine Whether a Food Allergen is of Public Health Importance

Food allergy is the result of a particular type of immune response against one or more food components, usually proteins. The food allergy reactions that are the focus of regulatory measures are mediated by antibodies of the IgE class. Importantly, food allergy is a two-step process. The first step, the sensitisation phase, consists of an immune response resulting in production of IgE antibodies specific for the allergen. The second step, the provocation phase, is the triggering of a symptomatic allergic reaction as a result of exposure to the allergen after sensitisation has been established. For reasons not well understood, a majority of sensitised individuals never will experience clinical reactions. Determining the number of sensitised individuals (test positives) in a population will therefore grossly overestimate the prevalence of food allergy. The term ‘allergy’ should be used only if clinical reactions occur. For triggering a food allergic reaction in a sensitised individual, only the ‘acute’ food intake and not the intake over time is of importance, and food allergy in this aspect resembles acute poisoning. Because of the cultural, agricultural, economic and nutritional importance of the foods, society accepts that a small fraction of the population develops allergies to traditional food products. Prevention of allergic reactions is then sought by means of education and by labelling of the most important allergenic foods. However, some 200 allergenic foods have been described, but only a small minority of these appears to be of importance in terms of frequency and severity of reactions triggered in the population. When it comes to management of the allergens, however, there is a lack of clear criteria at two levels: at the level of defining what documentation should be required to enter a proposed new food allergen into one of the large allergen databases, as well as at the level of determining which food allergens are of sufficient public health importance to require special regulatory attention in terms of labelling. With the aim of increasing transparency and predictability of decision-making processes and obtaining more consistency between labelling of different allergens as well as between labelling of allergens in different food regulatory jurisdictions, ILSI Europe has taken an initiative to establish clear criteria and a framework to determine the public health importance of a given food allergen. These criteria will consist of factors relating to food properties, population factors, and exposure factors.     

Suppression of immune responses to β‐lactoglobulin in mice by the oral administration of peptides representing dominant T cell epitopes

BACKGROUND: The significance of oral tolerance in the treatment of adverse immune reactions such as allergic and autoimmune diseases has been noted. In the present study, peptides that could effectively induce oral tolerance to bovine β‐lactoglobulin (BLG), a milk allergen, were investigated in a murine model. RESULTS: The oral administration of peptides corresponding to the T cell epitope regions of BLG, i.e. p42–56, p62–76 and p139–154, apparently down‐regulated T cell proliferation to BLG. The in vitro cytokine production by the lymph node cells from the peptide‐fed mice cultured in the presence of the antigen was also analysed. It was found that p62–76 and p139–154 feeding suppressed the production of both Th1 and Th2 types. Interestingly, p139–154 feeding suppressed both T cell and antibody responses to BLG. Additionally, p139–154 feeding diminished BLG‐specific IgE and IgG1 antibody responses. CONCLUSION: The unique tolerogen peptide p139–154 that could suppress both T and B cell responses to BLG in a murine model was identified. These findings can be useful for the selection of an optimum tolerogenic peptide to prevent and treat milk and other food allergies. Copyright © 2007 Society of Chemical Industry     

肠道菌群调控下的食物过敏机制研究进展

随着过敏人群数量的快速增加,食物过敏日益受到人们的关注。肠道微生物在机体免疫系统的形成和发展 中扮演着重要角色,越来越多的研究表明,抗生素的使用、膳食结构的改变等因素所引起的肠道菌群紊乱将会增加 人群患食物过敏的机率。本文将从细胞和分子水平综述目前对口服耐受的产生及因其缺失而引起食物过敏的相关机 理的研究,并在此基础上讨论肠道微生物调节食物过敏的潜在通路,最后概述有关益生菌缓解食物过敏的应用及机 制研究。通过了解肠道微生物与宿主黏膜系统的相互作用,可为预防及治疗食物过敏提供新的调控靶点和研究思 路,并为益生菌缓解食物过敏提供理论依据和改进方案,从而减少食物过敏的发生。     

重组乳酸乳球菌滴鼻免疫小鼠后粘膜免疫特性及耐

乳酸菌NICE(乳链菌肽控制表达nisin controlled expression,NICE)系统可将治疗性蛋白或保护性抗原蛋白表达于细胞外或锚定于菌体的肽聚糖上,递呈抗原蛋白并激活粘膜免疫系统,刺激特异性s-IgA的产生使其作为粘膜免疫原递呈的活载体成为可能。本试验将构建的重组乳酸乳球菌PNZ8149/NZ3900-M/PRRS鼻腔免疫BALB/c小鼠,检测呼吸道粘膜中抗体s-IgA和血清中特异性抗体IgG含量,评价其动态变化情况,同时检测脾脏细胞因子IL-4和IL-10的活性。结果重组乳酸乳球菌PNZ8149/NZ3900-M/PRRS免疫小鼠后,在测定时间内重组菌试验组小鼠呼吸道粘膜中特异性s-IgA水平高于对照组,差异极显著((P<0.01);血清中特异性抗体IgG水显著高于对照组((P<0.01);脾脏细胞悬液中的IL-10和IL-4含量与对照组无差异性(p>0.05),结果表明重组菌PNZ8149/NZ3900-M/PRRS经粘膜途径免疫小鼠后能能刺激小鼠粘膜特异性抗体s-IgA和血清中特异性抗体IgG的分泌,且能避免粘膜免疫耐受的产生,为该重组疫苗的进一步应用奠定了理论基础。     

Induction of oral tolerance, in mice, to gum arabic

As part of a programme of research on the immunological properties of the exudate gums, the capacity of gum arabic to induce immunologic hyporesponsiveness when fed (oral tolerance) has been examined. Inbred mice were fed saline or gum arabic; 1 week later all were systemically immunized with the antigen emulsified in complete Freund's adjuvant. Mice which had been fed the antigen had significant suppression of the humoral (P less than 0.01) and cell mediated (P less than 0.01) immune responses to the antigen. These results demonstrate that although gum arabic is a complex, proteinaceous polysaccharide antigen, it is tolerogenic when an animal encounters it by the natural route, via the gut.     

A review on the fate of pesticides during the processes within the food-production Chain

Only the intake of toxicologically-significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of residues in foods this is based on two major aspects--first, how to determine quantitatively the presence of a pollutant in individual foods and diets, including its fate during the processes within the food production chain; and second, how to determine the consumption patterns of the individual foods containing the relevant pollutants. The techniques used for the evaluation of the fate of pesticides during food processing have been critically reviewed in this paper to determine those areas where improvements are needed or desirable. Options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food pesticides, and harmonization of food consumption survey methods with the option of a regular pan-European survey. The ultimate aim is to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general. Existing pragmatic approaches are a first crude step to model food pollutant intake. It is recommended to extend, refine, and validate this approach in the near future. This has to result in a cost-effective exposure-assessment system to be used for existing and potential categories of pollutants. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.     

基于系统文献检索食品添加剂脱氢乙酸及其钠盐危害识别

本文基于系统性文献检索对食品添加剂脱氢乙酸及其钠盐进行危害识别。脱氢乙酸及其钠盐急性毒性属于低毒,其主要表现为中枢神经系统中毒症状;亚急性、亚慢性和慢性毒性主要表现为体重、进食量和其他生长指标明显降低,以及抗凝血作用;具有生殖发育毒性,主要表现为降低仔代体重及抑制骨骼发育。危害识别结果表明,脱氢乙酸及其钠盐经口暴露在一定剂量下可产生潜在毒性作用,目前亟需制定其健康指导值,为其作为食品添加剂使用的安全性评价提供依据。     

大米过敏的研究进展

食物过敏是机体针对摄入的食物产生的一种有害的、具有复发性的特定免疫反应,能够引起食物过敏反应的物质称为食物过敏原,食物中含有的致敏蛋白是引发食物过敏反应的一大来源。大米是世界上公认的最重要的粮食作物之一,全球约有一半以上的人口以大米为主食。大米蛋白占大米总量的8%~10%,含有丰富的必需氨基酸,易于被人体消化吸收,是公认的谷类蛋白中的上佳者。传统上认为,大米是低致敏性谷物,已被广泛应用于婴幼儿及配方食品中,但近年来的研究表明,大米也可引发食物过敏反应,可诱发过敏性皮肤炎、过敏性荨麻疹等症状,严重者还可引起过敏性休克。本文从大米过敏的流行性分布、主要的大米过敏蛋白以及过敏蛋白的检测方法等方面阐述了大米过敏的研究进展。     

Impairment of cellular immunity in west Greenland sledge dogs (Canis familiaris) dietary exposed to polluted minke whale (Balaenoptera acutorostrata) blubber

Minke whale (Balaenoptera acutorostrata) blubber is rich in organohalogen contaminants, mercury, and n-3 fatty acids. In the present study we show that a daily intake of 50-200 g of minke whale blubber causes an impairment of the nonspecific and specific cellular immune system in the West Greenland sledge dog (Canis familiaris). Immune reactions were measured by mitogen (PHA, Con A) and antigen (KLH) intradermal testing, and as the study used exposure levels similar to those of Inuits and polar bears (Ursus maritimus), it is reasonable to infer that Inuits and polar bears suffer from similar decreased resistance to diseases. It is speculated that food sources are depleted by thinning sea ice due to climate change and that more research should assess the forecasted rise in additive immunopathy effects in polar bears. Additionally, our study suggests that the fatty acid composition may be of importance when investigating combined immunotoxic effects of contaminated food resources in future Inuit and polar bear studies.