Complement factor H in host defense and immune evasion

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer

Sleep- and wake-like states in small networks in vivo and in vitro

Wakefulness and sleep are highly complex and heterogeneous processes, involving multiple neurotransmitter systems and a sophisticated interplay between global and local networks of neurons and non-neuronal cells. Macroscopic approaches applied at the level of the whole organism, view sleep as a global behaviour and allow for investigation into aspects such as the effects of insufficient or disrupted sleep on cognitive function, metabolism, thermoregulation and sensory processing. While significant progress has been achieved using such large-scale approaches, the inherent complexity of sleep-wake regulation has necessitated the development of methods which tackle specific aspects of sleep in isolation. One way this may be achieved is by investigating specific cellular or molecular phenomena in the whole organism in situ, either during spontaneous or induced sleep-wake states. This approach has greatly advanced our knowledge about the electrophysiology and pharmacology of ion channels, specific receptors, intracellular pathways and the small networks implicated in the control and regulation of the sleep-wake cycle. Importantly though, there are a variety of external and internal factors that influence global behavioural states which are difficult to control for using these approaches. For this reason, over the last few decades, ex vivo experimental models have become increasingly popular and have greatly advanced our understanding of many fundamental aspects of sleep, including the neuroanatomy and neurochemistry of sleep states, sleep regulation, the origin and dynamics of specific sleep oscillations, network homeostasis as well as the functional roles of sleep. This chapter will focus on the use of small neuronal networks as experimental models and will highlight the most significant and novel insights these approaches have provided