van Niekerk Gustav, Davis Tanja, Engelbrecht Anna-Mart
Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Matieland, Stellenbosch, 7600, South Africa.
Biol Direct. 2015 Sep 4;10:47. doi: 10.1186/s13062-015-0079-0.
The characterization of a completely novel adaptive immune system (AIS) in jawless vertebrates (hagfish and lampreys) presents an excellent opportunity for exploring similarities and differences in design principles. It also highlights a somewhat neglected question: Why did vertebrates, representing only 5 % of all animals, evolve a system as complex as an AIS twice, whereas invertebrates failed to do so? A number of theories have been presented in answer to this question. However, these theories either fail to explain why invertebrates would not similarly develop an AIS and are confounded by issues of causality, or have been challenged by more recent findings.
Instead of identifying a selective pressure that would drive the development of an AIS, we hypothesise that invertebrates failed to develop an AIS because of the evolutionary constraints imposed by these animals' physiological context. In particular, we argue that a number of vascular innovations in vertebrates allowed the effective implementation of an AIS. A lower blood volume allowed for a higher antibody titer (i.e., less 'diluted' antibody concentration), rendering these immune effectors more cost-effective. In addition, both a high circulatory velocity and the ability of endothelium to coordinate immune cell trafficking promote 'epitope sampling'. Collectively, these innovations allowed the effective implementation of AIS in vertebrates.
The hypothesis posits that a number of innovations to the vascular system provided the release from constraints which allowed the implementation of an AIS. However, this hypothesis would be refuted by phylogenetic analysis demonstrating that the AIS preceded these vascular innovations. The hypothesis also suggests that vascular performance would have an impact on the efficacy of an AIS, thus predicting a correlation between the vascular parameters of a species and its relative investment in AIS. The contribution of certain vascular innovations in augmenting immune functionality of an AIS can be tested by modelling the effect of different vascular parameters on AIS efficacy.
The hypothesis not only explains the immunological dimorphism between vertebrates and invertebrates but also brings to attention the fact that immunity is dependent on more than just an immune system.
无颌脊椎动物（盲鳗和七鳃鳗）中全新适应性免疫系统（AIS）的特征，为探索设计原则上的异同提供了绝佳机会。这也凸显了一个有些被忽视的问题：仅占所有动物5%的脊椎动物，为何两次进化出像适应性免疫系统这样复杂的系统，而无脊椎动物却没有？针对这个问题，已经提出了一些理论。然而，这些理论要么无法解释无脊椎动物为何没有类似地发展出适应性免疫系统，且被因果关系问题所混淆，要么受到了最新研究结果的挑战。
我们没有去寻找推动适应性免疫系统发展的选择压力，而是假设无脊椎动物未能发展出适应性免疫系统是由于这些动物生理环境所施加的进化限制。具体而言，我们认为脊椎动物的一些血管创新使得适应性免疫系统得以有效实施。较低的血容量使得抗体滴度更高（即抗体浓度“稀释”程度更低），使这些免疫效应器更具成本效益。此外，高循环速度以及内皮细胞协调免疫细胞运输的能力都促进了“表位采样”。总体而言，这些创新使得适应性免疫系统在脊椎动物中得以有效实施。
该假说假定血管系统的一些创新消除了限制因素，从而使得适应性免疫系统得以实施。然而，如果系统发育分析表明适应性免疫系统早于这些血管创新出现，那么这个假说将被推翻。该假说还表明血管性能会对适应性免疫系统的功效产生影响，因此预测一个物种的血管参数与其在适应性免疫系统上的相对投入之间存在相关性。通过模拟不同血管参数对适应性免疫系统功效的影响，可以检验某些血管创新在增强适应性免疫系统免疫功能方面的作用。
该假说不仅解释了脊椎动物和无脊椎动物之间的免疫二态性，还让人们注意到免疫不仅依赖于免疫系统这一事实。
