ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewThe lung has a unique relationship with the environment. Through evolution the lung has developed strategies to defend itself from microbial invasion. As we encounter increasing multidrug-resistant microorganisms, we need to further our knowledge of innate defense systems in order to design novel strategies to deal with these microbes without inducing over-exuberant inflammation and lung injury.Recent findingsThe development of lung innate immunity requires microbial molecular pattern recognition by the recently described Toll like receptors, the release of early response cytokines that further activate the ‘master switch’, nuclear factor-κB, leading to amplified host defense to invading microbes. A balance of Type 1 and Type 2 cytokines modulates the intensity of innate immunity. Cytokines/chemokines orchestrate the polarization and transition of innate to adaptive immunity.SummaryThe elucidation of the pathways involved in innate immunity and factors controlling the transition to adaptive immunity will improve our understanding of the host response to infection and improve our ability to design new therapies for the treatment of infectious disease.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewToll-like receptors (TLRs) are a family of pattern recognition receptors that are activated by specific components of microbes and certain host molecules. They constitute the first line of defense against many pathogens and play a crucial role in the function of the innate immune system. Recently, TLRs were observed to influence the development of adaptive immune responses, presumably by activating antigen-presenting cells. This has important implications for our understanding of how the host tailors its immune response as a function of specific pathogen recognition. The present review discusses the recent studies that demonstrate the role of TLRs in the regulation of adaptive T-helper-1 (Th1) and Th2 responses, and the mechanisms by which the effects are carried out.Recent findingsMost studies have focused on the role of TLRs and components of their signaling pathways in the control of Th1-type immune responses, and on the implications for their use as antimicrobial agents, such as adjuvants in vaccines, or to treat or prevent the Th2-type dominated immune responses seen in allergies. TLR-deficient mice have been described and used to come to these conclusions. Although controversial, there is also evidence that TLRs may be important for Th2-type responses, possibly by augmenting the overall maturity of dendritic cells.SummaryA greater understanding of the processes by which TLRs regulate adaptive immunity may yield not only improved ways to treat infectious diseases but also new approaches to the treatment and prevention of allergic and certain autoimmune disorders.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewCytokines have been implicated in the protective immunity, pathophysiology and development of tuberculosis. Most people who become infected withMycobacterium tuberculosismount an effective protective immune response, but 5-10% develop disease. Active pulmonary tuberculosis can be considered to reflect an ineffective immune response against mycobacterial infection. A better understanding of how cytokine production contributes to immunity and pathology would aid the development of new vaccines and therapeutic strategies.Recent findingsAt the time of diagnosis, production ofM. tuberculosisor mycobacterial antigen-induced interferon-γ by peripheral blood mononuclear cells from tuberculosis patients is usually depressed, compared with that of healthy control subjects, whereas cytokine production at the site of disease is elevated. In most patients, depressed interferon-γ production by peripheral blood mononuclear cells seems to be a transient response because it is significantly increased in most active tuberculosis patients during and following successful antituberculous therapy. However, some patients remain anergicin vivoandin vitroafter chemotherapy, and the underlying biochemical mechanisms for T cell anergy in modulating protection or pathology in tuberculosis needs further clarification. Among the cytokines contributing to protective immunity, interleukins 12 and 18, and tumour necrosis factor-α are important, the basis of recent studies with tuberculosis patients.SummaryA more complete understanding of cytokine dynamics in individual cells in active pulmonary tuberculosis patients will provide further knowledge about immunopathogenesis and protective immunity in human tuberculosis. This should ultimately enhance development of preventive and therapeutic strategies against this enormously successful intracellular pathogen.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewIt is now well established that cytokines play a critical role in the regulation of the immune system. Processes such as lymphoid development, differentiation, homeostasis, tolerance and memory are all regulated by cytokines that bind the type I family of cytokine receptors. Like the interferons, which bind receptors designated as the type II cytokine receptor family, type I cytokines also have essential functions in host defence.Recent findingsRecently, a number of new interleukins and their receptors have been discovered and their role in mounting an appropriate immune response is currently being studied. In this review we will describe the new interleukin-12 family of cytokines, which now includes two other members: interleukins 23 and 27. We will also review the newly discovered interleukins 28 and 29, also known as interferon-λs, which bind to the type II family of cytokine receptors, their structure and the structure of their receptors, their biological activities and modes of signalling.SummaryThese new molecules will certainly be the focus of active research in the immediate future. Their discovery opens the door to new therapeutic approaches to the treatment of various diseases ranging from infections from intracellular pathogens to viral infections.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Streptococcus pneumoniaeis a complex human pathogen and a major cause of morbidity and mortality. The genetic background of pneumococci and the chemical structure of their capsules is largely unraveled as well as the basic role of anticapsular antibodies and other opsonins interacting to enhance phagocytosis. Many experimental studies are improving our knowledge on the complex molecular mechanisms underlying those events. Pneumococcal optimal clearance requires the cooperation of a plethora of reactions from both innate and adaptive immunity. The last advances in the complexity of the immune response and protection are reviewed: phagocyte-pneumococcus interactions mediated by opsonins; the role of complement, reactive C protein and natural antibodies; details of novel immune evasion mechanisms; the complex role of the inflammatory mediators in the susceptibility to pneumococcal infections; why capsular polysaccharides do not yield an anamnestic response after primary immunization; the central question of whether T cells regulate in-vivo anti-polysaccharide immunoglobulin responses to intact pathogens. All of these are topics where new data and some answers are offered. The state of the art on the research of pneumococcal protein vaccines as an alternative to plain polysaccharide or conjugated vaccine and the establishment of immunologic correlates of protection to facilitate efficacy trial assessment are also reviewed.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewStaphylococcus aureusproduces two closely-related fibronectin-binding proteins (FnBPs) that facilitate attachment by this versatile pathogen. Recent studies of staphylococcal FnBP have increased our understanding of the molecular mechanisms that are critical in bacterial-host cell interactions and in infection.Recent findingsThis review will summarize current knowledge of the role of the FnBPs ofStaphylococcus aureusin the pathogenesis of infection. The FnBPs, which facilitate attachment of this pathogen to host cells and to fibronectin-coated biomaterials, are important mediators of infection in experimental endocarditis. In addition, recent vaccine studies utilizing FnBP derivatives have shown partial protection in animals. FnBPs also act as invasins permitting uptake of the staphylococcus by cultured non-professional phagocytes using host fibronectin to bridge with integrins on the cell surface. However, the precise role of FnBP in tissue invasion and the relevance of intracellular invasion in disease remain to be elucidated.SummaryFnBP is one of many adhesins expressed byS. aureusthat influence host tissue adherence by binding to host fibronectin. FnBP-based vaccine strategies and novel anti-adherence tools based upon FnBP derivatives are in the early stages of investigation but may show promise in preventing staphylococcal infections.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewMucosal immunization should be an excellent method of preventing respiratory infections because the local immunoglobulin A antibodies can neutralize the invading pathogens at the site of entry. BecauseStreptococcus gordonii, a normal inhabitant of the human oral cavity, can naturally elicit a mucosal immune response, it has been a prime candidate for investigations as a live oral vaccine vector for immunization against respiratory infections.Recent findingsAntigens from a number of respiratory bacteria, such asBordetella pertussis, and one virus have been expressed extracellularly or on the cell surface ofS. gordonii. The antigens expressed were single or multiple proteins from one or more pathogens. The recombinantS. gordoniiexpressing surface-localized heterologous antigens could colonize and persist in the oral cavity of mice and rats. Oral colonization induced a mucosal immunoglobulin A response and, in some instances, also a systemic immunoglobulin G response to the heterologous antigens. When given parenterally, the heterologous antigens generated a systemic immunoglobulin G response. These findings indicate that antigens expressed byS. gordoniiare immunogenic. A new approach to the use ofS. gordoniias a vaccine vector is to modulate immune responses by co-expressing cytokines with the antigen.SummaryThe ability to express antigens from respiratory pathogens and induce immune responses during oral colonization suggests thatS. gordoniimay be developed into a live vector for oral immunization against respiratory infections. The major challenge ahead is to find ways to achieve a high level of immune response following oral colonization.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Following the terrorist attacks on 11 September 2001 there has been increased concern about bioterrorism, much of it focused on smallpox. Routine smallpox vaccination in the USA was discontinued in 1972 and most US citizens are susceptible to smallpox. The last natural case of smallpox occurred in 1978 but the virus has been stocked in freezers. If a terrorist had access to stored smallpox virus a release could produce a chaotic situation. In response the USA has developed a program for vaccinating adults but children have been left out. The only available vaccine has recently been tested in adults but a proposal for testing children was not approved. We need to know if available vaccines are safe for children so children can be safely and effectively vaccinated in an emergency situation.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Purpose of reviewCaliciviruses are a major cause of human illness, and are listed as category B pathogens according to the National Institute of Allergy and Infectious Diseases classification of pathogens important for biodefense. Caliciviruses are commonly encountered in contaminated food and water, and a large variety has been implicated as sources of infection during outbreak investigations.Recent findingsNew names for two of the four genera of theCaliciviridaewere approved in 2002. They areNorovirus, for what were previously called Norwalk-like viruses or small, round-structured viruses, andSapovirus, for what were previously called Sapporo-like viruses. Caliciviruses are highly diverse genetically and antigenically. This diversity complicates the design of diagnostic assays, yet can be used to discriminate contaminating and infecting strains during outbreak investigations. Of particular interest is the recent finding of naturally occurring recombinantNorovirusstrains, all of which have been virulent and are widely dispersed and apparently ecologically indistinguishable from other calicivirus strains. This finding is considered in light of the evidence for recombination between caliciviruses and picornaviruses, and recombination as a more general phenomenon for virus evolution.SummaryContinued investigations of calicivirus outbreaks are now focusing on the implicated sources of infection. While many foods and environmental waters have long been implicated as outbreak sources, the methods for detecting caliciviruses are being developed and refined. Recognition is now turning to unexpected sources of contamination, such as presumably clean foods and waters, including bottled water and minimally handled foods. Parallels betweenNorovirusandSalmonellaecology and epidemiology are noted, as a guide to understanding evolving new information about caliciviruses.

ISSN:0951-7375    

出版商:OVID    

年代:2003

数据来源: OVID