Ontogeny of Immunity in Frogs/Thyroid Hormone Effects

之前对蝌蚪和成年南非爪蛙的免疫反应的研究表明，蝌蚪的反应通常较差，这表明免疫系统不成熟。由于免疫反应在变态后有所改善，而且这种改善似乎是甲状腺激素依赖的，因此可以推测，变态时激素的变化将幼虫的免疫系统转变为成虫类型的系统。具体地说，有人提出一群幼虫淋巴细胞在变态时被破坏，并在新一轮造血潮后被另一群将在成虫中发挥作用的淋巴细胞所取代。这些研究旨在进一步研究发育和变态期间低浓度甲状腺激素引起的免疫缺陷，更清楚地确定是否存在不同的幼虫淋巴细胞群，并研究变态期间甲状腺激素浓度的变化对假定幼虫种群的下降和成虫种群出现的影响。甲状腺和皮质类固醇激素对培养的变态前蝌蚪、变态蝌蚪和成年青蛙淋巴细胞的活性和功能的直接影响也将被研究。最后，一项对早熟变态蛙的第I类MHC抗原表达的研究将检验这一假说，即这些青蛙的皮肤移植排斥反应的改变是由于成体淋巴细胞群体在表达第I类抗原之前过早扩张所致。因为蝌蚪发育为自由生活的有机体，它们需要一个功能强大的免疫系统来保护它们免受环境病原体的侵袭。幼虫的免疫系统必须在变态过程中改变，以适应新的成虫特有的抗原，否则这些抗原将被认为是外来的，变态的蝌蚪将开始自我毁灭。了解免疫系统在变态时是如何变化的，以及各种变态相关激素在这些变化中的作用，应该会让我们更深入地了解自我认识和对自我的免疫耐受发展的过程。

Previous studies of the immune responses of tadpoles and adult South African clawed frogs, Xenopus laevis, have shown that tadpole responses are generally poorer, indicative of an immature immune system. Because immune responses improve after metamorphosis, and this improvement appears to be thyroxine dependent, it is postulated that the hormonal changes at metamorphosis transform the larval immune system to an adult- type system. Specifically, it is proposed that a population of larval lymphocytes is destroyed at metamorphosis and is replaced following a new wave of hematopoiesis by another population that will function in the adult. The studies proposed here are designed to examine further the immunological deficits that result from low thyroid hormone concentrations during development and metamorphosis, to establish more clearly whether a distinct larval lymphocyte population exists, and to examine the effects of altered thyroid hormone concentrations during metamorphosis on the decline of the putative larval population and emergence of the adult population. Direct effects of thyroid and corticosteroid hormones on the viability and function of cultured lymphocytes from premetamorphic tadpoles, metamorphosing tadpoles, and adult frogs will also be studied. Finally, a study of the expression of Class I MHC antigens in precociously metamorphosis frogs will test the hypothesis that altered skin allograft rejection responses in these frogs is due to premature expansion of the adult lymphocyte population prior to expression of Class I antigens. Because tadpoles develop as free-living organisms they need a functional immune system to protect them from environmental pathogens. The larval immune system must change during metamorphosis to accomodate new adult-specific antigens, or these antigens would be recognized as foreign and the metamorphosing tadpole would begin to destroy itself. Understanding how the immune system changes at metamorphosis and the role of various metamorphosis-related hormones in these changes should give us greater insight into the process by which self-recognition and immunological tolerance to self develop.