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]


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.]



Further articles in this publication

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

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


[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

[Models of immune recognition: presence and future]


[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.]

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

[Multiple interactions between heat shock proteins and innate immunity]


[Heat-shock proteins play essential roles in all living cells and their structure is highly conserved during evolution. Their expression is up-regulated in response to diverse stress stimuli and HSPs may function as a marker of danger. There are multiple processes in innate immunity to recognize HSP. Due to their strong recognition and conserved nature HSPs are immunodominant antigens in most of the bacterial infections and are therefore frequently key players in infection induced autoimmunity. The antigenic picture of HSPs is coded in the immunological homunculus in mammalian organisms and the maintenance of regulating autoimmunity protects against self-damaging processes.]

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Hungarian Immunology

[Gene therapy as a treatment for rheumatoid arthritis]

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[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.]

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[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.]