Hungarian Immunology

[Autoimmunity as a result of escape from RNA surveillance]

SEMSEI Imre, DARISE Farris, BACHMANN Michael

JANUARY 20, 2007

Hungarian Immunology - 2007;6(01-02)

[The pathomechanisms of autoimmune diseases are still unknown. Numerous factors are thought to play a role in the formation of the diseases (genetic arrangement, hormonal factors, exogen and endogen viruses, etc.) and many hypotheses have been formulated to explain the role of these factors. Most of the theories suspect that disturbance of the immune system is the clue but according to other researchers the immune system performs properly and one has to find other alterations that could be blamed for the formation of the autoimmune diseases. The aim of our present work is to show that certain genetic alterations together with the mistake of the RNA surveillance system could lead to autoimmune reactions. Results of immune research conducted in the past two decades revealed that there are mutations in the hot spot region of exon 7 of the La gene in the peripheral lymphocytes of patients suffering from certain autoimmune diseases (Sjögren's syndrome, SLE). RNAs originated from the mutant gene contain premature termination codon and therefore the RNA surveillance mechanism should get rid of these RNAs in order to prevent the formation of mutant proteins. However, because of the mistake of the surveillance system mutant proteins are formed that could finally lead to the autoimmune reactions.]

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[1,25 dihydroxyvitamin D3, the biologically active metabolite of vitamin D3 plays an important role not only in bone and calcium metabolism but in differentiation of many cells and in the immunomodulation. It exerts its biological effects via vitamin D receptor (VDR) expressed in antigen-presenting cells and activated T cells. VDR is a member of the superfamily of nuclear hormone receptors. The receptor- ligand interaction activates nuclear transcription factors or the receptor binds directly to vitamin D responsive elements in the promoter regions of cytokine genes. Dendritic cells (DC) are the primary targets of vitamin D3; it inhibits the differentiation and maturation of DCs, and hereby DC-dependent T cell activation. These immunomodulatory activities have been demonstrated in vitro and in different models of autoimmune diseases and transplantation in vivo. In this report we review the regulatory effects of active vitamin D3 on the immune system and the latest results emphasizing the immunomodulatory role of 1,25 dihydroxyvitamin D3 which might be utilized more in therapy.]

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[Accounting for about two-thirds of our white blood cells, neutrophilic granulocytes are key members of the innate immune system of the human body. They are terminally differentiated cells equipped with numerous antimicrobial weapons. Neutrophils are the first to arrive at sites of infections; their main mission is to phagocytose and destroy bacteria and funghi entering the human body. They fullfill a central role in both the inflammatory response of the body and the coordination of the innate and acquired immune systems’ function. Their deficient performance leads to impaired resistance of the host against microbes and to higher frequency of infections; their uncontrolled function, in turn, may damage our own tissues. Because of all of this, it is highly important from both basic and clinical perspective that we know as much as possible about the function of our neutrophilic granulocytes. In this paper methods available for measuring phagocytic and killing capacities of human neutrophils are reviewed. Each method has its advantages and disadvantages. The method chosen mainly depends on experimental tools available and informations needed.]

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