Download Free Investigating Complement Regulator Involvement In Innate Immune Evasion By Neisseria Gonorrhoeae Book in PDF and EPUB Free Download. You can read online Investigating Complement Regulator Involvement In Innate Immune Evasion By Neisseria Gonorrhoeae and write the review.

Antimicrobial resistant Neisseria gonorrhoeae (Ng) is an urgent threat to public health worldwide. Ng causes gonorrhea, the second most prevalent sexually transmitted bacterial infection. Left untreated, gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy, sterility, and in men can increase susceptibility to HIV. The current recommended treatment is a dual therapy with two antibiotics azithromycin and ceftriaxone. However, many countries are reporting cases with reduced effectiveness of this treatment method. This has placed a greater urgency on the development of preventative therapeutics. There is currently no commercial vaccine available for Ng infection. The development of preventative treatment strategies has long been impeded by Ng’s ability to evade the immune system, particularly the complement system. Ng is an obligate human pathogen and has evolved numerous mechanisms to interact with host-derived molecules that negatively regulate the activation of the immune system. Previous characterization of these mechanisms has focused on one class of complement inhibitors, fluid-phase inhibitors. To fully understand Ng immune evasion and the host molecules that contribute to it, investigating the role of the other class of complement inhibitors, membrane-associated complement inhibitors (mCIs) is needed. mCIs like CD46, CD55, and CD59 are expressed by human epithelial cells to prevent formation of the membrane attack complex on the surface of human cells. I hypothesized that these proteins may be sequestered by Ng during infection and create localized regions of immune activation allowing Ng to persist. To test this, we used a co-culture serum bactericidal assay (ccSBA) where human epithelial cells were infected with Ng, treated with normal human serum, a vehicle for the components of the complement system, and monitored bacterial viability over time. Using the ccSBA we demonstrated that increasing host expression of mCIs resulted in higher levels of Ng survival, while decreasing mCI expression resulted in lower Ng survival. We then used CRISPR to knock out all three of CD46, CD55, and CD59 simultaneously. Surprisingly, this had the opposite effect of what we expected, resulting in a substantial increase in Ng survival. We observed that the lack of mCIs rendered host cells susceptible to complement and speculated that this could result in the release of host-derived molecules that stimulated an alternative mechanism of Ng immune evasion. We used a strain of Ng deficient in this alternative mechanism and found that the absence of mCI expression resulted in a significant reduction in Ng survival. Finally, we expressed each of CD46, CD55, and CD59 individually and found that all three could support Ng survival alone. In summary, this dissertation shows that mCIs are involved in Ng immune evasion. Further it demonstrates the value of the ccSBA in investigating the role of host-derived molecules in Ng immune evasion.
The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Endotoxins are potentially toxic compounds produced by Gram-negative bacteria including some pathogens. Unlike exotoxins, which are secreted in soluble form by live bacteria, endotoxins are comprised of structural components of bacteria. Endotoxins can cause a whole-body inflammatory state, sepsis, leading to low blood pressure, multiple organ dysfunction syndrome and death. This book brings together contributions from researchers in the forefront of these subjects. It is divided into two sections. The first deals with how endotoxins are synthesized and end up on the bacterial surface. The second discussed how endotoxins activate TLR4 and, in turn, how TLR4 generates the molecular signals leading to infectious and inflammatory diseases. The way endotoxins interact with the host cells is fundamental to understanding the mechanism of sepsis, and recent research on these aspects of endotoxins has served to illuminate previously undescribed functions of the innate immune system. This volume presents a description of endotoxins according to their genetic constitution, structure, function and mode of interaction with host cells.
The comparative approach to immunology can be traced to the era of Pasteur and Metchnikov in which observations regarding foreign recognition in invertebrates was a factor in the develop ment of the principal concepts that created the foundation of what now is the broad field of immunology. With each major experimental and conceptual breakthrough, the classical, albeit essential, question has been asked "are the immune systems of phylogenetically primitive vertebrates and invertebrates similar to that of mammals?" Somewhat surprisingly for the jawed verte brates, the general answer has been a qualified form of "yes", whereas for agnathans and invertebrate phyla it has been "no" so far. The apparent abruptness in the appearance of the immune system of vertebrates is linked to the introduction of the somatic generation of the diversity of its antigen specific receptors. Therefore the questions regarding the origin and evolution of the specific immune system revolve around this phenomenon. With respect to the origin of the system (aside from the or igin of the rearranging machinery itself, the study of which is still in its infancy) one can ask questions about the cellular and mo lecular contexts in which the mechanism was introduced.
This authoritative, single-source reference provides comprehensive examinations of the complement system-offering recent findings in basic science on the structure, biology, physiology, and pathophysiology of complement proteins and the latest therapeutic approaches towards the control of complement-mediated diseases. Written by over 40 international experts from North America, Europe, and Asia, The Human Complement System in Health and Disease describes the molecular architecture of the complement system details the structure of complement genes discusses gene organization as well as the topology and chemistry of ligand-binding sites and catalytic centers of complement proteins analyzes complement organization and activation, including phylogeny and the newly discovered lectin pathway elucidates the regulation of complement gene expression and the structure and function of bioactive peptides explicates opsonic and immunoregulatory properties of complement fragments, endothelial responses, and interactions with viruses and bacteria and more!
The Immune Response is a unique reference work covering the basic and clinical principles of immunology in a modern and comprehensive fashion. Written in an engaging conversational style, the book conveys the broad scope and fascinating appeal of immunology. The book is beautifully illustrated with superb figures as well as many full color plates. This extraordinary work will be an invaluable resource for lecturers and graduate students in immunology, as well as a vital reference for research scientists and clinicians studying related areas in the life and medical sciences. - Current and thorough 30 chapter reference reviewed by luminaries in the field - Unique 'single voice' ensures consistency of definitions and concepts - Comprehensive and elegant illustrations bring key concepts to life - Provides historical context to allow fuller understanding of key issues - Introductory chapters 1-4 serve as an 'Immunology Primer' before topics are discussed in more detail
Lyme disease (Lyme borreliosis) is the most prevalent vector-borne illness in the United States and Europe and a growing threat to global health. In addition Lyme disease is considered a model system of emerging infectious diseases. The book Borrelia: Molecular Biology, Host Interaction and Pathogenesis published in 2010 was the first state-of-the-art reference work covering the myriad, interlaced facets of the enzootic disorders caused by pathogenic Borrelia. This current volume, by the same editors, builds on the previous work and contains a vast amount of new information, a wider scope, and increased coverage of genomics, genetics, evolutionary biology, vector biology, physiology, pathogenicity, immune response, and immune evasion. Written by renowned scientists who have made seminal contributions to the field, this book contains an expansive treatment of the options to track live spirochetes and evaluate gene expression in ticks and mice, provides insights into the workings of the flagellar motor, presents up-to-date research on the modulation of gene expression, and reviews recent studies on the Lyme disease spirochete's networks of regulatory pathways. The volume highlights and describes in detail the tremendous advances in understanding of the Borrelia genus at the molecular and cellular levels as well as the pathogenesis of Lyme disease and relapsing fever. This comprehensive volume is indispensable for anyone involved in Borrelia and Lyme disease research and is highly recommended for microbiologists, immunologists, and physicians with an interest in spirochetes, vector-borne illness, or emerging infectious diseases. The book is a recommended reference volume for all microbiology libraries.
This book provides a comprehensive, state-of-the-art review of the concepts vital to a modern treatment of common and opportunistic infections in the immunocompromised host. Chapters are written by experts in the field, and include their views on gaps in the field and future directions of research. This book begins with an overview of the normally functioning immune system followed by a detailed discussion of the major primary immunodeficiencies. Specific chapters are dedicated to providing practical knowledge in the prevention and treatment of infections in specific immunocompromised patients, including those with cancer, transplant recipients, HIV infection, and autoimmune disorders. Emphasis is placed on diagnostic evaluation, antimicrobial selection that includes consideration of the threat of antimicrobial-resistant pathogens, and immunotherapy tailored to specific patients. Finally, dedicated chapters on stem cell transplantation for patients with primary immunodeficiencies, adoptive cellular immunotherapy, and gene therapy will provide readers with insight into these rapidly evolving and cutting edge therapies.Management of Infections in the Immunocompromised Host is a valuable resource for infectious diseases specialists, immunologists, oncologists, hematologists, general physicians, students, researchers, and all other working with immunocompromised patients.
A comprehensive compendium of scholarly contributions relating to bacterial virulence gene regulation. • Provides insights into global control and the switch between distinct infectious states (e.g., acute vs. chronic). • Considers key issues about the mechanisms of gene regulation relating to: surface factors, exported toxins and export mechanisms. • Reflects on how the regulation of intracellular lifestyles and the response to stress can ultimately have an impact on the outcome of an infection. • Highlights and examines some emerging regulatory mechanisms of special significance. • Serves as an ideal compendium of valuable topics for students, researchers and faculty with interests in how the mechanisms of gene regulation ultimately affect the outcome of an array of bacterial infectious diseases.
Chagas disease causes severe socioeconomic impact and a high medical cost in Latin America. WHO and the World Bank consider Chagas disease as the fourth most transmittable disease to have a major impact on public health in Latin America: 120 million persons are potentially exposed, 16 to 18 million of whom are presently infected, causing 45,000 to 50,000 deaths per year. It has been calculated that approximately 2.4 million potential working years are lost because of incapacity and mortality due to the disease, for an annual cost estimated at 20 billion Euros. American Trypanosomiasis provides a comprehensive overview of Chagas disease and discusses the latest discoveries concerning the three elements that compose the transmission chain of the disease: - The host: human and mammalian reservoirs - The insect vectors: domestic and sylvatic vectors - The causative parasite: Trypanosoma cruzi - Informs and updates on all the latest developments in the field - Contributions from leading authorities and industry experts