Hungarian Immunology

[The role of Toll-like receptors in the early steps of innate inmunity. Signaling pathways, responses on the level of cells and the organism]

PRECHL József

AUGUST 20, 2003

Hungarian Immunology - 2003;2(04)

[The family of Toll-like receptors are currently one of the most intensively studied group of proteins in immunology. Their ligands include a wide range of microbe-derived molecules, they are expressed on a number leukocyte populations and regulate immune responses very efficiently. In this review we characterize known common and individual signaling pathways of the receptor family and their interference with effects of other receptors, and describe the outcome of TLR signaling on the level of the cells and the organism.]

COMMENTS

0 comments

Further articles in this publication

Hungarian Immunology

[The role of the complement system in the primary recognition processes and in the regulation of adaptive responses]

ERDEI Anna

[It is known for long that the complement system present in blood and other body fluids is able to kill pathogenic microbes as a result of activation. It is also well-known that certain complement components enhance phagocytosis by opsonizing foreign substances. In addition to these roles, recent experimental results point to novel functions of certain complement proteins/receptors, namely to their contribution to the development and regulation of the adaptive response and their capacity to influence the interaction between the innate and the adaptive immune systems. During these processes certain proteins of the complement system recognise non-self structures and distinguish them from the body’s own constituents/cells. This step initiates the activation of the cascade generating several biologically active molecules, which then regulate various immune reactions.]

Hungarian Immunology

[Pathogen-associated molecular pattern of bacteria and its recognition by the host]

KOCSIS Béla, EMÕDY Levente

[Pathogen-associated molecular pattern of bacteria is determined by a molecular complementarity between the host and the microorganism. The process of pathogenesis is initiated through recognition of bacterial components or products by receptor molecules of the host organism. Constant structural components like the lipopolysaccharide in Gramnegative and lipotheichoic acid in Gram-positive bacteria are recognised by receptor molecules present in a wide range of host species, and in this way they elicit interactions and pathologic processes generally present in bacterial infections. At the same time accessorial components (adhesins, capsular material) or extracellular products (exotoxins, enzymes) mediate specific interactions which determine host species or organ specificity according to the molecular structure of the virulence factor and the specific host/organ receptor. The pathogen-associated molecular pattern is subject to changes as genom plasticity in bacteria allows evolution of virulence through recombinations and pathoadaptive mutations. Actual expression of accessorial virulence factors is frequently governed by complicated regulatory mechanisms as an adaptative response to environmental stimuli present in the host.]

Hungarian Immunology

[Biologic therapies in the vasculitides]

SZÁNTÓ Antónia

Hungarian Immunology

[Our archaic heritage: the innate immunity. The cellular immunity of Drosophila]

ANDÓ István, LAURINYECZ Barbara, NAGY István, MÁRKUS Róbert, FLORENTINA Rus, VÁCZI Balázs, ZSÁMBOKI János, FEHÉR László, ELISABETH Gateff, DAN Hultmark, KURUCZ Éva

[Authors describe the essentials of the cellular immunity of Drosophila. They describe the Drosophila CD system, the main blood cell lineages and a blood cell differentiation model based on the expression of the CD antigens.]

Hungarian Immunology

[Models of immune recognition: presence and future]

GERGELY János

[The prevailing theories of immune recognition for over 50 years were based on the idea that the immune system functions by discriminating self and nonself. Since the self-nonself theories failed to explain a number of immune phenomena new models were suggested, such as the ”infectious nonself” and the ”danger” models. The review outlines and compares these models of immune recognition.]

All articles in the issue

Related contents

Lege Artis Medicinae

[The pain-trigger role of cytokines in the nervous system – the direct analgesic effect of anti-cytokine therapy ]

HODINKA László, VERECKEI Edit

[Nociceptive, neuropathic and central me­chanisms are involved in the perception, transmission and processing of chronic pain and shaping of cerebral pain image. Alar­mins – molecules alarming defence and signing the presence of pathogens and tissue damage - trigger a series of pathogenic events resulting in inflammatory pain stimuli. Proinflammatory cytokines play a determining role in the pain perception at the level of the nervous system. Continuous inflammatory stimuli while sensitizing the periferic and central neurons activate the pain-related cerebral areas and develop the complex pain image, the pain matrix. Ce­reb­ral functional connections are operating in networks and can be visualized by functional MRI. Cytokines activate the neurons directly or indirectly by other neuromediators. Cytokine receptors are expressed on no­ciceptors and even on higher-level neurons and on various non-neural cells, such as microglia and astrocytes. The most ubiquitous cytokines are the Tumour Necrosis Factor and Interleukin 6 in the nervous sys­tem. The signaling pathways are the Nuclear Factor κB and the Janus-kinase enzyme system. The proinflammatory cytokines and the Janus-kinase are therefore primary therapeutic targets. Anti-cytokine biologicals and small molecular kinase inhibitors decrease the pain and improve functional activity in rheumatoid arthritis. Decrease of pain was more pronounced than expected only from the decrease of the clinical biomarkers of inflammation. The early and ra­pid painkiller effect of targeted biological and chemical-biological response modifiers is attributed to their direct analgesic effect on the brain.]

Hungarian Immunology

[Gene therapy as a treatment for rheumatoid arthritis]

JAMES M. Woods

[A clear understanding of the pathogenic events and/or environmental conditions that lead to the development of rheumatoid arthritis has not been accomplished. In recent years, some of the most capable therapies have targeted individual proteins, such as proinflammatory cytokines, which contribute to persistent inflammation. The success of these therapies in some patients underscores the importance of having a solid pathophysiologic knowledge of the mechanisms at play in the diseased joint. Targeting the joint therapeutically with proteins or other agents has presented many challenges in the treatment of rheumatoid arthritis. To circumvent these obstacles, the idea of providing transgenes to cells of the synovial lining was born. This use of gene therapy, as a delivery vehicle rather than replacement of a genetic deficit, has had many successes in preclinical animal studies. Preliminary results of the first Phase I clinical trial in humans suggests that an ex vivo approach can be safe and enable transgene expression. This review provides a consolidated overview of many of the successful gene therapy strategies undertaken for the treatment of animal models of arthritis. The focus is on: 1. joint targeting strategies, including discussion on the local and systemic approaches as well as the contralateral joint; 2. the applicability of viral vectors, including comparison of adenoviral, retroviral, adeno-associated, and herpes simplex viruses; 3. timing and dosage of treatment; and 4. targets and candidate proteins that have been examined, including targeting proinflammatory cytokines or the use of anti-inflammatory cytokines.]

Hypertension and nephrology

[About the care of patients with hyperuricaemia and gout]

[This consensus document is intended to provide guidance for the effective and efficient treatment of asymptomatic individuals with high uric acid levels and gout patients.]