Host Immune Strategies: Remembering, Resisting, Tolerating, and Being Specific

寄生虫可以对宿主产生强烈的负面适应性影响。这对宿主产生了强大的选择压力，使其具有有效的免疫系统。免疫系统应该能够识别和区分许多不同的寄生虫，并以最大限度地提高宿主适应性的方式做出反应。一般来说，这导致两种不同的防御策略：抵抗和容忍。抗性预期会导致宿主和寄生虫之间的对抗性协同进化。然而，人们对宽容如何影响共同进化知之甚少。除了不断进化的防御，在其一生中，宿主先前的寄生经验也会影响其防御的有效性。事实上，一些无脊椎动物可以表现出类似于脊椎动物免疫记忆的现象，对不同的寄生虫具有意想不到的特异性。在这个提议中，我们将从两个角度研究果蝇中的宿主-寄生虫相互作用。首先，我们将解决以前的寄生虫的经验，并确定它是否会影响抵抗力和耐受性的策略，这可能会对宿主-寄生虫的共同进化产生影响，并有助于了解生活史的限制。第二，我们解决了一个潜在的遗传基础识别特定的寄生虫抗原，通过测试的作用，假定的免疫受体，Dscam（唐氏综合征细胞粘附分子）。该基因在遗传和体细胞水平上是大量多样化的，因此它被假设可以提供特异性免疫应答所需的多样性。我们还将联合收割机特异性免疫与耐受性相结合，并确定该基因是否影响寄生虫抗性和耐受性。我们希望这些实验将提供深入了解宿主-寄生虫相互作用的生态学和进化，特别是在抗性，耐受性和免疫特异性的背景下。

Parasites can have strong negative fitness effects on their hosts. This creates a powerful selection pressure on a host to have an efficient immune system. The immune system should be able to recognise and discriminate between many different parasites, and respond in a way that maximises host fitness. Broadly speaking, this results in two different defence strategies: resistance and tolerance. Resistance is expected to lead to antagonistic coevolution between the host and the parasite. However little is known about how tolerance can affect coevolution. As well as evolving defences, within its lifetime the previous parasite experience of the host can also influence the effectiveness of its defences. Indeed some invertebrates can show a phenomenon similar to vertebrate immune memory, with an unexpected degree of specificity towards different parasites. In this proposal we will examine host-parasite interactions in the fruit fly, Drosophila melanogaster, from two perspectives. First we will address previous parasite experience and determine whether it affects the strategies of resistance and tolerance, which could have implications for host-parasite coevolution and help to understand life-history constraints. Second we address a potential genetic basis for recognition of specific parasite antigens, by testing the role of the putative immune receptor, Dscam (Down syndrome cell adhesion molecule). This gene is massively diversified at the genetic and somatic level, and as such it has been hypothesised that it could provide the diversity necessary for specific immune responses. We will also combine specific immunity with tolerance and identify whether this gene influences parasite resistance and tolerance. We hope that these experiments will provide insight into the ecology and evolution of host-parasite interactions, specifically in the context of resistance, tolerance and immune specificity.