传统观点认为,胎儿的免疫系统极为脆弱,对病毒只能作出基本的反应,根本无法达到一般成年人所具有的能精准定位的防御水平。然而,最近美国科学家的研究打破了这一观点。
来自哥伦比亚大学过敏症学家和免疫学家Rachel Miller相信,胚胎免疫系统比研究人员想象的要高级的多。
Miller与其同事征集了126名妊娠期间接受过禽流感疫苗注射的126名孕妇为志愿者。这些妇女生产时,Miller采集每位新生儿的脐带血样本,共得到70个可用样本,并利用一种从未在脐带血中应用的技术在细胞水平观察免疫反应。他们一个细胞一个细胞地鉴别,是否胚胎在对流感疫苗的反应中产生特定抗体。他们发现40%的样本含产生了能够攻击流感病毒的抗体和T细胞。Miller说,还不清楚的是为何只有某些胚胎呈现了免疫反应,但她说值得注意的是存在流感特异抗体,一些是体积过大无法从母体通过胎盘到达胎儿的IgM抗体,这意味着它们无疑是胎儿产生的。这一成果刊登于6月1日《Clinical Investigation》。
来自威斯康星大学麦迪逊分校(University of Wisconsin-Madison)的免疫学家William Burlingham说:"这表明,从诞生那刻起,婴儿便具有了一个较成熟的免疫系统。"
虽然胎儿的免疫系统是否强大到足够抵御病毒的侵扰还有待证实,但是这些免疫细胞的存在已经表明,这种新生的免疫系统能够产生免疫细胞以对抗特定的抗原。
来自哈佛医学院的内科医生及免疫学家Ofer Levy说,如果新生儿由此真的具有了抵抗病毒的能力,那么这项研究成果将对公众健康产生重要的意义。他说:"如果优化疫苗,那么你将能够增加同时保护母亲和新生儿的可能性。"
胎儿通过胎盘,从母体处获得长达6个月的抗体供应,为其抵抗充满敏感诱发颗粒和病毒的外部世界进行武装。最新研究结果提示发育过程中的胎儿能够对来自母体的流感疫苗进行特异免疫反应。这项发现有助于结束围绕胚胎免疫系统复杂性的争论。
威斯康星州立大学免疫学家Aimen Shaaban说,这项成果证实了“胚胎可以进行特定免疫反应”的长期争论的理论,是该领域的一颗重磅炸弹。但他也强调,疫苗接种在三个月时进行,因为那时的胚胎免疫系统有时间变得更复杂。Shaaban说认为,重复工作有助于观察早期trimesters时的胚胎,确定这种先进的免疫系统反应开始工作的确切时间。
原始出处:
J. Clin. Invest. 117:1637-1646 (2007). doi:10.1172/JCI29466.
Research Article
Antigen-specific immune responses to influenza vaccine in utero
Deepa Rastogi1, Chaodong Wang2, Xia Mao3, Cynthia Lendor3, Paul B. Rothman4 and Rachel L. Miller3
1Children’s Hospital at Montefiore, Albert Einstein College of Medicine, New York, New York, USA. 2Department of Neurology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of China. 3Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA. 4Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
Address correspondence to: Rachel L. Miller, PH8C, Columbia University College of Physicians and Surgeons, 630 W. 168th Street, New York, New York 10032, USA. Phone: (212) 305-7759; Fax: (212) 305-2277; E-mail: rlm14@columbia.edu .
Received for publication June 21, 2006, and accepted in revised form April 9, 2007.
Abstract
Initial immune responses to allergens may occur before birth, thereby modulating the subsequent development of atopy. This paradigm remains controversial, however, due to the inability to identify antigen-specific T cells in cord blood. The advent of MHC tetramers has revolutionized the detection of antigen-specific T cells. Tetramer staining of cord blood after CMV infection has demonstrated that effective CD8+ antigen-specific immune responses can follow intrauterine viral infections. We hypothesized that sensitization to antigens occurs in utero in humans. We studied cord blood B and T cell immune responses following vaccination against influenza during pregnancy. Anti-Fluzone and anti-matrix protein IgM antibodies were detected in 38.5% (27 of 70) and 40.0% (28 of 70), respectively, of cord blood specimens. Using MHC tetramers, HA-specific CD4+ T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father. Matrix protein–specific CD8+ T cells were detected among 10.0% (2 of 20) of HLA-A*0201+ newborns. These results suggest that B and T cell immune responses occur in the fetus following vaccination against influenza and have important implications for determining when immune responses to environmental exposures begin.