黏膜免疫反应与呼吸道过敏性疾病

黏膜免疫是近年来倍受关注的免疫学新理论之一,促使人们对黏膜免疫有了新认识。黏膜免疫系统是由黏膜相关淋巴样组织（MALT）组成。黏膜上皮细胞持续不断地接触外环境中微生物及过敏原等刺激物,发挥着黏膜免疫屏障保护性防御功能,作为机体对抗外来刺激物的第一道防线,以保障机体内环境的稳定。     

The effects of maternal smoking on early mucosal immunity and sensitization at 12 months of age

With the dramatic rise in asthma and respiratory disease, there is an urgent need to determine the effects of common environmental exposures on early immune development. In this study, we examined the effects of maternal smoking as a major adverse exposure in early life, on mucosal immune function and allergen sensitization in the first year of life. A cohort of 60 smokers and 62 non-smokers was recruited in pregnancy, and followed prospectively at 3 and 12 months of age for saliva collection [for immunoglobulin (Ig) A measurements], urine collection (for cotinine levels) and clinical assessments (for allergy and infection history). Allergen skin-prick tests were also performed at 12 months of age. Specific IgA to common colonizing bacteria was measured on saliva samples, including pneumococcal polysaccharide (PS) serotype 14 and non-typeable Haemophilus influenza (NTHI) outer membrane protein 6 (OMP6). Eighty-two mothers and their infants completed the 12-month follow-up period--56 in the maternal non-smoking group and 26 in the maternal smoking group. Maternal smoking was associated with significantly higher total infant salivary IgA at 12 months of age (p = 0.026), and more chronic upper respiratory tract symptoms (p = 0.012). However, there were no differences in the level of specific IgA antibodies to common colonizing bacteria (pneumococcal PS serotype 14 and NTHI OMP6). In general, the IgA levels at 12 months were higher in children who had more chest infections in the first year (Kendall's tau b, 0.282; p = 0.003). There was also a trend of lower respiratory tract symptoms (wheeze) (p = 0.142) in infants of smokers. There were no effects of maternal smoking on the rates of allergen sensitization, atopic dermatitis and food allergy at 12 months of age. In conclusion, maternal smoking did not inhibit the production of anti-microbial IgA, suggesting that other factors are responsible for the increased susceptibility to infection in these infants. The increased mucosal inflammation in these children was not associated with effects on early allergy propensity.     

Mucosal Neuromas and Plexiform Neurofibromas: An Immunocytochemical Study

Mucosal neuromas (MN), a component of multiple endocrine neoplasia (MEN) type IIb, may be confused histologically with plexiform neurofibromas (PN), a component of neurofibromatosis. The ability to distinguish between these two markers for different genetic diseases is crucial, as the risk of development of medullary thyroid carcinoma and pheochromocytoma in affected patients with MEN IIb is great. We studied two cases each of MN and PN by immunocytochemistry (IC). Epithelial membrane antigen (EMA) proved to be the most useful marker. MN consisted of bundles of disorganized and tortuous nerve fibers surrounded by a thickened perineurium that expressed the cellular phenotype EMA(+), S-100(-). PN consisted of enlarged neroe fascicles with a loose myxoid stroma and was EMA negative. Thus, IC highlighted the differing pattern of growth and histogenesis of the proliferating cells in the two lesions and is likely to be especially useful in those lesions with atypical histology.     

短链脂肪酸与食物过敏的肠道黏膜免疫

食物过敏的发病机制、诊断标准以及治疗方案仍需进一步探究.短链脂肪酸是肠道菌群的代谢产物之一,关于其免疫调节作用的研究逐渐增多并且已经应用于某些免疫相关疾病的临床治疗.为全面了解短链脂肪酸对食物过敏的肠道黏膜免疫调节以及潜在的治疗作用,文章综述了食物过敏的肠道黏膜免疫机制、短链脂肪酸与食物过敏的联系,以及短链脂肪酸在其中...     

Th17细胞在肠黏膜免疫中的作用

肠黏膜是人体最大的淋巴器官,它与呼吸道黏膜、泌尿生殖道黏膜等一起构成机体的第一道防御体系.肠黏膜经常抵御细菌、病毒、食物抗原、非甾体类抗炎药等的侵袭,若肠黏膜免疫系统遭受破坏,机体发生感染性疾病、自身免疫性疾病等.因此,肠黏膜免疫功能正常对机体的健康非常重要.Th17细胞是近年来发现的一类不同于Th1和Th2细胞的T细...     

Mucosal receptor for IgA in the breast-fed neonate

Immunoglobulin A from human milk binds to neonatal buccal cells. Pretreatment of the cells with anti-secretory component antiserum blocks this binding, suggesting that secretory component (SC) contributes to the adhesive process. The concentrations of SC in saliva of preterm neonates is lower than that of full-term infants. This may lower the effectiveness of mucosal immunity passively transferred from the mother.     

Current issues regarding the use of pneumococcal conjugate and polysaccharide vaccines in Australian children

OBJECTIVE: To present the results of child pneumococcal vaccination studies in the setting of current Australian disease epidemiology and immunization policy, and issues that clinicians should consider in discussions with families. METHODS: This paper includes a narrative review of randomized, controlled, double blind studies and systematic reviews which evaluated the efficacy of child pneumococcal vaccination. RESULTS: 7PCV is expected to prevent > 80% of childhood invasive pneumococcal disease (IPD, includes meningitis, septicaemia/bacteraemia) and the associated mortality. 7PCV may prevent 6% of all pneumonia, 18% of radiographically-defined pneumonia, 6% of all otitis media (OM) and 20%-40% of tympanostomy tube procedures. It may also reduce IPD due to antibiotic-resistant pneumococci, and prevent IPD in unvaccinated individuals. The impact of replacement disease caused by non-vaccine serotypes is not yet known. Pneumococcal polysaccharide vaccines given to 2-year-old children may prevent approximately 19% of all and 26% of recurrent OM. CONCLUSION: The Australian Standard Vaccination Schedule recommends universal infant immunization with seven-valent pneumococcal conjugate vaccine (7PCV). Universal infant 7PCV will prevent pneumococcal diseases and deaths. The potential for its impact to be reduced in the long-term by serotype replacement must be closely monitored. Information concerning disease epidemiology, vaccine efficacy and safety, disease risk perception and national costs may prove useful in discussions with families.     

THE MUCOSAL IMMUNE RESPONSE IN THE NEONATE

Hanson LÅ, Brinton C, Carlsson B, Dahlgren U, Mellander L, Sutton A and Söderström T. (Departments of Clinical Immunology and Paediatrics, University of Göteborg, Sweden, Bureau of Biologies, FDA, Bethesda, and Department of Life Sciences, University of Pittsburg, USA). The mucosal immune response in the neonate. Acta Paediatr Scand, Suppl. 296:53, 1982. — Human infants are relatively deficient in the IgA system defending mucosal membranes, but are provided via the maternal milk with considerable amounts of SIgA directed against microbes and food antigens to which both mother and infant are exposed. It is possible that serum antibodies may support the mucosal defense as do the lactoferrin, lysozyme and other defense factors present in the milk.     

Challenges in developing mucosal vaccines and antibodies against infectious diarrhea in children

Infectious diarrhea in children can be life‐threatening and imposes a large economic burden on healthcare systems, therefore more effective prophylactic and therapeutic drugs are needed urgently. Because most of the pathogens responsible for childhood diarrhea infect the gastrointestinal mucosa, providing protective immunity at the mucosal surface is an ideal way to control pathogen invasion and toxic activity. Mucosal (e.g. oral, nasal) vaccines are superior to systemic (subcutaneous or intramuscular) vaccination for conferring both mucosal and systemic pathogen‐specific immune responses. Therefore, great efforts has been focused on the development of cost‐effective mucosal vaccines for the past 50 years. Recent progress in plant genetic engineering has revolutionized the production of inexpensive and safe recombinant vaccine antigens. For example, rice plant biotechnology has facilitated the development of a cold‐chain‐free rice‐based oral subunit vaccine against Vibrio cholerae. Furthermore, this technology has led to the creation of a rice‐based oral antibody for prophylaxis and treatment of rotavirus gastroenteritis. This review summarizes current perspectives regarding the mucosal immune system and the development of mucosal vaccines and therapeutic antibodies, particularly rice‐based products, and discusses future prospects regarding mucosal vaccines for children.     

母乳喂养与新生儿免疫

新生儿的免疫系统尚不成熟。母乳中含有多种具有抗感染作用的生物活性成分,如sIgA、乳铁蛋白、溶菌酶、低聚糖、游离脂肪酸、白细胞及细胞因子等,能为新生儿提供免疫保护。母乳的部分成分还可能与促进新生儿免疫发育有关,而母乳中的抗原成分和细胞因子则具有诱导免疫耐受的作用。     

Measles,mumps, rubella (vaccine) and varicella vaccines in pediatric liver transplant: An initial analysis of post‐transplant immunity

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post‐transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy‐two (22%) patients were measles non‐immune, and 42/67 (63%) were varicella non‐immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27‐27.41) and technical variant graft (OR 0.07, 95% CI 0.01‐0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30‐11.01). This study demonstrates that non‐immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non‐immunity in this high‐risk population.     

Innate and adaptive immunity in necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most frequent and devastating gastrointestinal disease of premature infants. Although the precise mechanisms are not fully understood, NEC is thought to develop following a combination of prematurity, formula feeding, and adverse microbial colonization. Within the last decade, studies increasingly support an important role of a heightened mucosal immune response initiating a pro-inflammatory signaling cascade, which can lead to the disruption of the intestinal epithelium and translocation of pathogenic species. In this review, we first describe the cellular composition of the intestinal epithelium and its critical role in maintaining epithelial integrity. We then discuss cell signaling during NEC, specifically, toll-like receptors and nucleotide oligomerization domain-like receptors. We further review cytokines and cellular components that characterize the innate and adaptive immune systems and how they interact to support or modulate NEC development.     

Meningococcal A, C, Y and W-135 polysaccharide-protein conjugate vaccines

Serogroup C meningococcal conjugate vaccines, first launched in the UK in 1999, have been used successfully in Australia, Canada and several other European countries. Combination conjugate vaccines, containing more than one meningococcal polysaccharide, have been developed to broaden protection against the disease. A tetravalent meningococcal A, C, Y and W-135 conjugate vaccine was licensed for use in 11-55 year old adolescents and adults in the US in January 2005, and subsequently also in 2-11 year old children in Canada in May 2006. This article discusses the different glycoconjugate meningococcal vaccines which have been developed and the potential for their use to control disease caused by serogroups A, C, Y and W-135 of Neisseria meningitidis.     

Dysfunction of innate immunity and associated pathology in neonates

The neutrophils and complement system are the critical elements of innate immunity mainly due to participation in the first line of defense against microorganisms by means of phagocytosis, lysis of bacteria, and activation of naive B-lymphocytes. In this report we provide an overview of the up to date information regarding the neutrophil and complement system’s functional ability in newborn infants in association with the maternal conditions that exist during the intrauterine stage, gestational age and post-neonatal pathology. The neonates’ capacity to control the neutrophil and complement protein activation process has also been discussed because of the evidence that uncontrolled activation of these immune elements provides a significant contribution to the tissue damage and subsequent pathology. The authors are confident that despite the many unanswered questions this review updates their knowledge and points the need for further research to clarify the role of the age-associated dysfunction of neutrophils and complement system in the infection and inflammation related pathology of newborn infants.     

Nineteen cases of persistent pruritic nodules and contact allergy to aluminium after injection of commonly used aluminium-adsorbed vaccines

Rare cases of persistent pruritic nodules, sometimes associated with aluminium (Al) allergy, have been reported after the use of several Al adsorbed vaccines. During vaccine trials in the 1990s a high incidence of pruritic nodules (645 cases/76,000 recipients), in 77% associated with Al allergy, was observed after the administration of diphtheria–tetanus / acellular pertussis (DT/aP) vaccines from a single producer. In the present report 19 children with pruritic nodules after vaccination with Al hydroxide-adsorbed DTaP/polio+Hib (Infanrix, Pentavac) are described. The children had intensely itching nodules at the injection site, often aggravated during upper respiratory tract infections, and local skin alterations. So far, the symptoms have persisted for up to 7 years. The median time between vaccination and onset of symptoms was 1 month. 16 children were epicutaneously tested for Al, all with positive reactions indicating delayed hypersensitivity to Al. The condition is not commonly known but is important to recognise, as the child and the family may suffer considerably. Future vaccinations with Al-adsorbed vaccines may cause aggravation of the symptoms and the Al allergy. Al-containing skin products, such as antiperspirants, may cause contact dermatitis. Nodules may be mistaken for tumours. Even though the incidence of itching nodules and Al allergy after administration of Infanrix, Pentavac and other Al-adsorbed vaccines is probably low, research to replace Al adjuvants seems appropriate. We conclude that intensely itching subcutaneous nodules, lasting for many years, and hypersensitivity to aluminium may occur after DTaP/polio+Hib vaccination of infants.     

Developmental aspects of cell-mediated immunity and findings in low birth weight infants

The development and maturation of immunity is a series of timed steps beginning with the epithelial outgrowth of the thymus from the third branchial pouch. Lymphoid cells, probably of extrathymic origin, populate the anlagen around the 6th week gestation. This is followed by the ability to respond to allogenic cells and later on to mitogens. The acquisition of surface markers occurs around the 10–11th week gestation. In the newborn, the absolute number of T cells is comparable to that in older children. However, the ability to mount delayed hypersensitivity reactions is impaired. The synthesis of some lymphokines is normal whereas that of others is reduced. Fetal growth retardation due to variety of causes can result in severe deficits in cell-mediated immunity of the newborn. This impairment may persist for several months to years, despite adequate nutrient intake in postnatal life. Infection, maternal ingestion of drugs and many other factors can affect the normal development of the immune system.     

Immunoglobulin G subclasses in human colostrum, milk and saliva

Previous studies have suggested local production of IgG4 in human colostrum and mature milk. We extended these observations to examine all IgG subclasses in mammary secretions and in saliva, a mucosal secretion. In human colostrum and milk, the geometric mean percentages of IgG contributed by IgG2 were 44% and 43%, respectively, and by IgG4, 6% in both. These percentages are significantly increased compared to the contributions in matched plasma, 29% for IgG2 and 2% for IgG4. The contribution of IgG1 (47%) and IgG3 (less than 4%) were decreased compared to plasma which contained 64% IgG1 and 6% IgG3. Similarly, in salivary secretions the percentages of IgG contributed by IgG2 and IgG4 were increased compared to serum while the percentage of IgG1 was decreased. IgG3 was not measurable in any saliva specimen by the technique used. These data demonstrate that IgG subclass distribution in two separate mucosal secretions is uniquely different from that in matching plasma or serum.     

Effect of persuasive messaging about COVID-19 vaccines for 5- to 11-year-old children on parent intention to vaccinate

Aim

Uptake of COVID-19 vaccines for children aged 5–11 years old in Australia has plateaued. Persuasive messaging is an efficient and adaptable potential intervention to promote vaccine uptake, but evidence for its effectiveness is varied and dependent on context and cultural values. This study aimed to test persuasive messages to promote COVID-19 vaccines for children in Australia.

Methods

A parallel, online, randomised control experiment was conducted between 14 and 21 January 2022. Participants were Australian parents of a child aged 5–11 years who had not vaccinated their child with a COVID-19 vaccine. After providing demographic details and level of vaccine hesitancy, parents viewed either the control message or one of four intervention texts emphasising (i) personal health benefits; (ii) community health benefits; (iii) non-health benefits; or (iv) personal agency. The primary outcome was parents' intention to vaccinate their child.

Results

The analysis included 463 participants, of whom 58.7% (272/463) were hesitant about COVID-19 vaccines for children. Intention to vaccinate was higher in the community health (7.8%, 95% confidence interval (CI) −5.3% to 21.0%) and non-health (6.9%, 95% CI −6.4% to 20.3%) groups, and lower in the personal agency group (−3.9, 95% CI −17.7 to 9.9) compared to control, but these differences did not reach statistical significance. The effects of the messages among hesitant parents were similar to the overall study population.

Conclusion

Short, text-based messages alone are unlikely to influence parental intention to vaccinate their child with the COVID-19 vaccine. Multiple strategies tailored for the target audience should also be utilised.     

巨细胞病毒肝炎患儿细胞免疫功能变化和干扰素的临床疗效

目的研究巨细胞病毒（ＨＣＭＶ）肝炎患儿细胞免疫功能是否受损；经治疗后临床症状恢复期中免疫功能的恢复情况；干扰素对巨细胞病毒肝炎的疗效。方法用ＤＮＡ探针斑点原位杂交，酶兔方法检查ＨＣＭＶ抗原，尿中分离ＨＣＭＶ３种方法诊断ＨＣＭＶ肝炎。用ＩＬ－２活性测定、Ｔ细胞亚群测定检测患儿细胞免疫功能，将患儿分为干扰素加维生素Ｃ、肌苷治疗组（γＩＦＮ）和仅用维生素Ｃ、肌苷治疗组（非γＩＦＮ），连续观察３个月临床症状恢复情况。结果ＨＣＭＶ肝炎患儿有明显的细胞免疫功能损伤，且临床症状缓解后部份免疫功能尚不能完全恢复。干扰素治疗组的临床症状恢复和第１月与第２月的痊愈率明显优于无干扰素治疗组。黄疸消退平均提前１４．９天（Ｐ＜０．０５）；肝肿大恢复正常提前２８．４天（Ｐ＜０．０１），ＳＧＰＴ恢复正常平均提前１４．９天（Ｐ＜０．０１）。两组的第１月与第２月痊愈率分别为４８．６％与２０．６％、８８．６％与４７．１％（Ｐ＜０．０５）。结论ＨＣＭＶ患儿细胞免疫功能均受损，且不能随症状好转而立即全部好转。干扰素能使ＨＣＭＶ患儿的临床症状加快消退。     

小剂量补充锌剂对学龄前儿童血清锌水平及细胞免疫功能的影响

为观察补充锌剂对学龄前儿童体内锌水平以及细胞免疫功能的影响 ,对143名学龄前儿童进行了为期6个月的对照观察 ,其中补锌组88名 ,对照组55名。每天补充10mg元素锌。6个月后 ,补锌组儿童的血清锌浓度从12.8μmol/L±1.87μmol/L提高到15.4μmol/L±1.68μmol/L(P<0.01) ;并明显高于对照组14.4μmol/L±1.20μmol/L(P<0.01) ;此外 ,对其中血清锌浓度低下的40名儿童 ,补锌组25名 ,对照组15名 ,用流式细胞技术分析补充锌剂前后T细胞亚群的变化 ,结果显示补锌组儿童的CD4 +细胞从37.3 %±4.54%上升到39.6 %±3.36 %(P<0.01),CD8 +细胞从26.7 %±5.07 %上升到28.2 %±4.66 %(P<0.01)。表明小剂量补充锌剂能改善儿童的锌营养状况及免疫功能 ,可能有助于减少感染性疾病的发生