Uday Kishore - Böcker

Target pattern recognition in innate immunity is responsible for the immediate, usually protective, responses shown against invading microorganisms, and it is the principal feature of self and non-self recognition by virtue of the recognition of structures on the microbial pathogens, which are not found on host cells. This is an area that has been very actively researched, over approximately the past 12 years, and therefore this volume provides a timely comprehensive, and up to date, summary of the types and range of cell surface, intracellular, and secreted, host proteins involved in the recognition of microbial products, and of the protective mechanisms triggered as a result of the recognition events.The Toll-like receptors, first described in Drosophila and now well-characterised on human cells, provide an excellent demonstration of the wide range of different microbial products recognised by this family of receptors and of the signalling pathways which are triggered thus leading to induction of inflammatory cytokines and the activation of genes producing antimicrobial products. In addition, several cell surface proteins involved in target pattern recognition have been described on the surfaces of macrophages (macrophage mannose receptor and macrophage scavenger receptors), and on dendritic cells (DEC205), and to be involved with the uptake and clearance of whole microorganisms and polyanioic ligands. Pattern recognition is also utilised by intracellular receptors, with NOD-like receptors in the cytosol recognizing microbial molecules and activating the production of inflammatory cytokines or pathways that induce the production of inflammatory molecules. Secreted proteins, such as the pentraxins, which includes the acute phase reacting, C-reactive protein (CRP) and serum amyloid protein (SAP), and the collectins (mannan binding lectin, lung surfactant protein A and D) and ficolins can also readily recruit killing and clearance systems. Indeed, the serum complement system, which is one of the major defence systems in the bloodstream, is efficiently activated by CR P on its binding to the phosphocholine groups of microbial phospholipids—and the subsequent interaction of the bound CR P with C1q—to give classical pathway activation, or MBL, or ficolin, binding to arrays of mannose or N-acetyl-glucosamine residues, respectively, on the surfaces of microorganisms—to give lectin pathway activation. Also, in addition to the activation and clearance events associated with complement activation by some of the secreted pattern recognition receptors, it is accepted that all these pattern recognition receptors can generally accelerate the uptake and clearance of microbes via phagocytic cells.In view of the growing interest in the cross-talk between innate and adaptive immunity, a thorough understanding of the initial recognition and triggering events, mediated via innate immune receptors, as addressed in this volume, is clearly very useful in helping to also fully understand the mechanisms of activation and control of the adaptive immune system—and to allow a full assessment of the relative roles played by innate immunity and adaptive immunity against a particular infection in higher organisms.

The book starts with dissecting mechanisms underlying viral immune evasion via exploiting the host complement system by vaccinia virus, and by modulating the type 1 interferon response by RNA viruses. Yet another chapter looks into how viroporins expressed by different families of viruses causing influenza A virus, SARS, hepatitis C and HIV interact with several cellular pathways. Understanding of these mechanisms can aid the development of novel potential anti‑viral targets. The chapter on tuberculosis discusses the emerging importance of the innate immune mechanisms against Mycobacterium tuberculosis infection and latency. This book has a strong focus on fungal pathogenesis and immunity, starting with virulence and host factors that attain great importance in candidiasis and associated escape tricks of seriously opportunistic fungi. Two chapters on Aspergillus fumigatus elaborate on the pathogenic mechanisms: first discussing A. fumigatus‑airway epithelium interaction, followed by fungal and host factors that are paramount in the development of allergic and invasive aspergillosis. In the subsequent chapter, there is a general discussion on the innate and adaptive immune responses against primary and opportunistic fungal pathogens.

The topic of this book, Collectins, is a family of proteins whose major function is in innate immunity, where Collectins act as pattern recognition receptors (PRRs). In general they recognize targets such as microbial surfaces and apoptotic cells, and once bound to a target, Collectins promote the clearance of microorganisms and damaged host tissue. New cell-surface proteins and glycoproteins, which act as Collectin receptors, are currently being identified. Some Collectins, particularly MBL, activate the complement system, which enhances the ability of antibodies to fight pathogens, via three MBL-associated proteases, the MASPs. Additionally, recent research has begun to show wider-ranging activities of Collectins, such as: ·         Their role in metabolism, and therefore their involvement in lifestyle diseases such as obesity and cardiovascular disease.·        Their ability to modulate the adaptive immune response, as well as to recognize and trigger apoptosis of cancer cells, which makes them effective in the annihilation of cancer cells with multiple mutations.·         The regulation of their expression by gonadal steroid hormones implicates them with critical roles in both male and female fertility.·         Altered levels of Collectins have been associated with various autoimmune diseases.This book brings together current knowledge of the structure, functions and biological activities of Collectins, to describe their integral role in human health.

This book updates in detail the microbial pathogenesis of various important pathogens, including HIV-1, MERS, SARS-CoV-2, Mycobacterium and Plasmodium. The overall purpose of the book is to aid in the development of anti-viral and anti-microbial targets.

This contributed volume follows up and expands upon Target Pattern Recognition in Innate Immunity (2009), providing a much-needed update on an area that has surged to the forefront of medical research in recent years.