Microbial Subversion of Immunity: Current Topics | Book
Caister Academic Press
Peter J. Lachmann and M.B.A. Oldstone Centre for Veterinary Science, Madingley Road, Cambridge CB3 0ES, UK and The Scripps Research Institute, La Jolla, CA 92037, USA (respectively)
vi + 292
March 2006Buy hardback
GB £159 or US $319
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Microbes have evolved an impressive and diverse range of strategies to subvert the host immune system. Two major types of strategies exist. The first is the evasion of recognition by the host for example by using antigenic variation, masking of epitopes, the use of decoys, molecular mimicry, etc. The second is the modulation and/or suppression of the innate (e.g. complement, NK cells) and adaptive (e.g. antibodies) immune responses. A better understanding of the underlying mechanisms involved is critical for the rational design of novel therapeutic agents and vaccines to treat and/or prevent infectious diseases. Another area of active research is the application of microbial immunomodulatory factors in the treatment of human immunological disorders (e.g. inflammatory bowel disease and asthma) and as sources of pharmacologically active agents.
In this book internationally renowned scientists critically review the current cutting-edge research in this area. Topics covered include the subversion of complement, NK cell function, mucosal innate immune response, evasion/subversion mechanisms used by bacteria, helminths, viruses, and the measles model system. Containing over 1,700 references, this book is an essential resource book for researchers in the fields of microbiology, immunology, pharmacology and molecular medicine.
"the authors and editors deserve much credit for producing a work that should be the reference standard in the field for some time." from Doody's (2006)
"... contains a collection of excellent reviews of the different mechanisms used to subvert host immunity by bacteria, viruses and helminths. Each chapter reads well and reveals very extensive sourcing of material ... an excellent information source" from Microbiology Today (2006)
"... a comprehensive introduction to the subject of microbial subversion of the immune response" from Antiviral Chemistry and Chemotherapy (2006) 17: 291
"each chapter in the book is individually excellent" from Clin. Inf. Dis (2007) 44: 157
"... an essential resource book for researchers in the fields of microbiology, immunology, pharmacology and molecular medicine." from CAB Abstracts (2006)
Subversion of Complement
Complement is probably the most important arm of the innate humoral immune system and virtually all pathogens invading the human host are attacked by it directly following entry and usually also during consecutive stages of disease, especially when they are in contact with blood. In order to escape or subvert the destructive action of complement, both its direct action and the interplay with the phagocytic system, most micro-organisms have developed an effective battery of specific strategies in order to survive the hostile environment within the host. The measures to avoid recognition and destruction by complement via complement-mediated attraction, opsonisation and activation of phagocytic cells, and lysis involves microbial molecules which are expressed on the surface or secreted into the near vicinity and can therefore be considered as virulence factors. Of all these highly sophisticated mechanisms imitation (molecular mimicry) and employment of host complement proteins appear to be the most evolutionary elaborated.
Microbial Subversion of NK Cell Function
Stipan Jonjic and Ulrich Kosinowski
Natural killer (NK) cells play a crucial role in the resistance to several viruses and other intracellular pathogens. They are among the first cells to sense the release of proinflammatory cytokines, as well as the perturbations in the expression of MHC class I molecules and other surface molecules induced by microbial invasion of cells. One of the best illustrations of the importance of NK cells is represented by the various microbial functions evolved to counter NK cell response. Here we summarize the major mechanisms and receptors that NK cells can employ to positively recognize and kill virus-infected cells and the range of microbial strategies that reduce the efficacy of NK cell activation and their effector functions. The elements for viral NK cell- subversions are mainly based on the assumption deriving from numerous findings in readily controlled in vitro systems whereas the evidence for their relevance in vivo are still only fragmentary. The murine model of cytomegalovirus infection highlights the biological importance of these viral immunoevasins. The analysis of the viral proteins will continue to provide important details on the diversity of mechanisms by which NK cells can be activated and modulated.
Mucosal Innate Immune Response
The innate immune system provides the first line of defence against invading micro-organisms. Most infectious agents infect their host through a mucosal surface, be it the digestive, respiratory or reproductive tract. The innate immune system comprises cellular activities stimulated by the recognition of pathogens by pattern recognition receptors (PRRs) in response to pathogen-associated molecular patterns (PAMPS) together with a multitude of secreted soluble antimicrobial factors. In order to protect themselves from this array of defences and to promote survival within the host, micro-organisms have developed a number of different counter measures. These include modification of bacterial cell membranes or cell walls, mimicry of host cell membrane lipids, secretion of proteins or enzymes that inhibit or degrade antimicrobial factors, and down-regulation of expression of antimicrobial substances. This chapter describes the various strategies adopted by both the host and invader on the battleground of mucosal surfaces.
Viral Immune Evasion: An Overview
The presence in the immunocompetent host of numerous mechanisms to prevent the infection by pathogens has forced successful viral pathogens to acquire during evolution strategies to evade the host defense mechanisms. Our knowledge of viral immune evasion strategies has expanded enormously during the last ten years, with viral evasion mechanisms identified for most of the known immune pathways. These studies are relevant to understand viral pathogenesis and shed light into basic mechanisms of immunity.
Overview of the Evasion Mechanisms Used by Bacteria
Michael M. Frank
This chapter reviews some aspects of molecular mimicry used in evasion strategies of bacteria. For long term survival a bacterium must occupy a niche where it can survive, reproduce and spread. Pathogenic bacteria in invading man must deal with a wide assortment of innate and adaptive host defense responses and have themselves evolved a wide variety of bacterial protective mechanisms. In many cases this involves the use of the host's cellular or biochemical pathways to subvert the host attack. For example, a mammalian host has evolved sophisticated mechanisms to separate self from non-self so that attack on host structures by innate and adaptive immune responses with resultant tissue damage is minimized. Some bacteria have evolved mechanisms to disguise themselves as self, thereby thwarting the host defense process. In similar ways bacteria use host structures for invasion of cells and tissues and intracellular survival. Analysis of these mechanisms has often led to the finding of convergent evolution, the evolution of bacterial elements that have similar function to host elements but unique structure. In some cases there is actual incorporation of host genes by horizontal transfer. There is almost no aspect of the host defense process that some group of organisms has not subverted for pathogenic use.
Subversion of the Immune Response by Helminths
Michael J. Doenhoff
Many years ago it was observed that helminth parasites were immunosuppressive and this property was deemed to be an important element in the ability of these organisms to evade host immune responsiveness and thus establish enduring chronic infections. Subsequent studies on anti-helminth immunity played a significant part in increasing our knowledge about the complexity and range of immune effector mechanisms, particularly by helping to distinguish between two sup-populations of T helper cells. Recent research has taken an unexpected turn that stems from observations that these parasites can exert profound modulatory (rather than merely suppressive) influences on host immune responsiveness. Possibilities of using infections of, and factors from these parasites to ameliorate human immunological disorders such as inflammatory bowel disease and asthma, and as sources of pharmacologically active agents, are now being actively explored.
Viral Subversion of Humoral Immune Responses
Man Sun Law , Pietro Paolo Sanna and Dennis R. Burton
Viruses are a group of hugely diverse organisms. Many viruses have developed strategies to subvert host immunity to enhance their fitness to propagate in a specific host. This review focuses on the strategies different viruses use to evade the humoral immune responses, with an emphasis on virus neutralizing antibodies (NAbs). The strategies used by viruses to subvert NAb responses targeting the virus surface (SU) proteins include (i) mutation by antigenic drift and shift, and recombination; (ii) masking of conserved epitopes; (iii) glycan shielding; (iv) SU protein decoys; (iv) original antigenic sin; (v) irregular SU protein spacing; and (vi) multiple SU proteins and virus forms. Viruses also evade humoral responses by spreading directly between cells, up-regulating and hijacking host complement regulatory proteins, encoding antagonistic Fc and complement receptors, and inducing immunosuppression. Understanding these mechanisms will provide valuable information for the design of anti-viral therapy and vaccines.
Viruses and Dendritic Cells: A Prominent Mechanism for Subverting the Immune Response
Elina Zuniga, Kurt Edelmann and Michael Oldstone
Viruses have evolved multiple strategies to counteract host immune responses. The essential role played by DCs in host defense to pathogens makes them an ideal choice for viruses to suppress the immune response and maximize their chances of survival, replication and transmission. Indeed many viruses that cause diseases and major health problems are able to interfere with the ability of DCs to prime an efficient and effective anti-viral immune response. By analogy to human viral infections, lymphocytic choriomeningitis virus (LCMV) infection in its natural host (the mouse) provides a convenient and powerful model system to study how viruses influence the DC compartment, avoid immunological surveillance and cause a persistent infection. In this chapter we briefly review the DC fundamental role during immune response, the several strategies of human viruses to subvert DC function and finally we describe in more detail the DC-virus interaction and its consequences in the LCMV murine model system.
Subversion of the Immune System by Measles Virus: A Model for the Intricate Interplay Between a Virus and the Human Immune System
Denis Gerlier, Hélène Valentin, David Laine, Chantal Rabourdin-Combe, and Christine Servet-Delprat
Despite the development of a successful live attenuated vaccine, measles remains one of the major infectious diseases with high mortality in developing countries and continuing outbreacks in other nations. A major physiopathological feature of measles infection is the concomitance of the induction of a long lasting efficient anti-viral immune response and a profound immunosuppression with impairment of humoral and cellular immune response to unrelated antigens. The analytical analysis of natural infection in human and experimental disease in monkeys allied to the discovery of many cellular proteins recruited by viral proteins has led to partly uncover many molecular and cellular mechanisms which govern the measles virus interplay with the human immune system. Indeed, this model of immune subversion by a pathogen has been thoroughly studied for many years and has led to some seminal findings dealing with the regulation of the immune system.
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(EAN: 9781904455059 Subjects: [bacteriology] [virology] [microbiology] [medical microbiology])