instruction:
In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
question:
We live in a hostile environment, surrounded by microbial pathogens and subject to a range of physical and chemical insults. To survive in this environment, vertebrates have evolved complex immune systems. A key element of this defence is the deployment of rapid response elements at the most probable sites of attack, which are the epithelial-cell boundaries between the body and the environment in the skin, gut and lungs. As the body's largest and most exposed interface with the environment, the skin has a central role in host defence. Before the relatively recent discovery of the immunological defences of skin, the cutaneous interface was viewed as a passive barrier between the host and the hostile environment. In the past few decades, however, it has become apparent that the mechanical aspects of epidermal defence are reinforced by a versatile and robust system of immune surveillance 1 (FIG. 1) . The crucial role of immune surveillance in maintaining homeostasis is evident from the marked increase in the frequency and severity of cutaneous malignancies and infections when immune function is limited, for example in patients with genetic and acquired immunodeficiency disorders and in those receiving immunosuppressive therapy after organ transplantation 2,3 . The regulation of skin defence mechanisms is also crucial, as inappropriate or misdirected immune activity is implicated in the pathogenesis of a large variety of acquired inflammatory skin disorders, including psoriasis, atopic and allergic contact dermatitis, lichen planus, alopecia areata and vitiligo 4-10 . The role of immune dysfunction in these conditions is emphasized by their response to immunosuppressive therapeutic interventions [11] [12] [13] [14] . Understanding the mechanisms of immune surveillance in the skin and tissue-specific immune responses also has important implications for the rational design of vaccines. To promote protective immunity, an immunization protocol must elicit not only an antigenspecific immune response, but also an effective memory response that will provide long-lived protection at the most probable sites of invasion. This applies equally to immunization against infectious organisms, which in most cases invade through the skin or the epithelia of the gastrointestinal or respiratory systems, and to the elicitation of immune responses against tumours. As we discuss, the route and means of adjuvant stimulation that is used can affect the effectiveness and utility of specific vaccine strategies. In this review, we discuss these issues in the context of recent advances in our understanding of cutaneous immune mechanisms, highlighting the interaction of The skin, as the primary interface between the body and the environment, provides the first line of defence against a broad array of microbial pathogens and trauma. In addition to its properties as a physical barrier, the skin has many active defence mechanisms. In this review, we discuss the interaction between the innate and adaptive immune systems in the skin as a model for immune function at epithelial-cell interfaces with the environment. How these mechanisms account for the robust nature of cutaneous immune surveillance and how their dysregulation drives the pathogenesis of inflammatory skin disorders and skin-based tumours are the subjects of this review.
answer:
IMMUNE SURVEILLANCE IN THE SKIN: MECHANISMS AND CLINICAL CONSEQUENCES


question:
Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNAsynthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3 -to-5 exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost longterm replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14's interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme's role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.
answer:
The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity


question:
In the older adult the benefits of vaccination to prevent infectious disease are limited, mainly due to the adaptive immune system's inability to generate protective immunity. Age-dependent decline in immune competence, often referred to as immunosenescence, results from progressive deterioration of innate and adaptive immune responses and most of the insights into mechanisms of immune aging have derived from studies in murine models. In this Review, we explore how well these models are applicable to understand the aging process throughout the 80-100 years of human life and discuss recent advances in uncovering and characterizing the mechanisms underlying age-associated defective adaptive immunity in humans.
answer:

Understanding immune senescence to improve vaccine responses