Wyniki wyszukiwania - Biblioteka Nauki

1

The innate cellular responses to HIV-1 invasion: emerging molecules of ancient defense mechanisms

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Simm M.

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nr 3

131-138

EN

Along alternative protective pathways, human cells can synthesize biologically active proteins that interfere with HIV replication, but are not viral antigen specific. HIV is sensitive to several viral inhibitors of cellular origin, such as interferons or interferon-regulated proteins. With the progress of AIDS research it has become evident that the immune cells of some individuals are capable of restricting the virus by secretion of other, yet unidentified factor(s) that can be detected only by their potent antiviral activity. Research efforts to identify this inhibitor of HIV ? a ?magic bullet' released by our immune cells ? have revealed the identity of several novel molecules and added to the knowledge of innate cellular responses to viral invasion.

2

Effect of cyclosporine A on the nonspecific, innate antiviral immunity of mice

100%

Zaczynska E. , Blach-Olszewska Z.

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2001

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tom 49

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nr 1 suppl.

53

EN

Different infections are the most common complication of immunosuppressive therapy. In this context, the effect of cyclosporine A (CsA) on the innate antiviral immunity of mice was studied. The presence of immunity was shown by infection of resident peritoneal cells (RPC) of BALB/c mice with herpes virus type 1 (HSV-1) and vesicular stomatitis virus (VSV). While the cells infected immediately after isolation were resistant to the viruses, the cells cultured for several days before infection lost immunity. The lack of activity to neutralize HSV-1 and VSV in the sera of the mice excluded a participation of specific antibodies in the resistance. To study the effect of CsA on innate immunity, BALB/ c mice were intraperitoneally (i. p.) injected with cyclosporine (20 or 100 mug/ mouse, twice a day) for three days. The other group of animals was injected in the same way with PBS only. Then the peritoneal cells were isolated and infected with VSV immediately after cell isolation. The kinetics of viral replication in the control and the CsA-treated groups was compared. While in the cells from the control group VSV did not multiply, in the cells from the CsA-treated mice the virus reached considerable titers. The cyclosporine effect on VSV replication was dose-dependent and statistically significant. We conclude that innate antiviral immunity was suppressed in the cyclosporine-treated mice and that this mechanism may be involved in the high susceptibility of patients to viral infections during immunosuppressive therapy.

3

Cytokine production by human leukocytes with different expressions of natural antiviral immunity and the effect of antibodies against interferons and TNF-alpha

100%

Orzechowska B. , Antoszkow Z. , Siemieniec I. , Lorenc M. , Jatczak B. , Blach-Olszewska Z.

Archivum Immunologiae et Therapiae Experimentalis

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2007

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tom 55

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nr 2

111-117

EN

Introduction: Two activities of innate antiviral immunity were studied: the resistance of human peripheral blood mononuclear cells (PMBCs) ex vivo to viral infection and the production of cytokines. Materials and Methods: Samples of blood were taken from healthy blood donors and from persons with frequent infections of the upper respiratory system. PMBCs were isolated by gradient centrifugation. Vesicular stomatitis virus (VSV) was used as the indicatory virus to infect PMBCs. The cytokines: IFN, TNF, and IL-6 were titrated by biological methods and IL-10 by ELISA. Results: Blood donors were divided for two groups: those with VSV-resistant and those with VSV-sensitive PMBCs and secretion of cytokines by them was compared. The resistant PMBCs produced more cytokines than the sensitive ones. A statistically significant difference, was found only in the case of the IFNs. To examine the contribution of IFNs and TNF in maintaining resistance, leukocytes from both groups were treated with specific anti-cytokine antibodies. The authors' previous study showed that the elimination of spontaneous IFN-alpha IFN-beta, IFN-gamma, and TNF-alpha from resistant leukocytes resulted in increased VSV replication This indicates the important role of cytokines. In VSV-sensitive PMBCs, anti-IFN-alpha showed the opposite effect (decreased virus replication). In the absence of spontaneous IFN-alpha, disturbances in cytokine production were observed. Conclusions: Complete resistance of PMBC to VSV infection is accompanied by higher cytokine release, The paradoxical effect of anti-IFN-alpha on virus replication in leukocytes sensitive to viral infection may be attributed to changes in the cytokine profile balance, i.e. high TNF production by VSV-infected leukocytes and a complete reduction of IL-6 production.

4

Innate immunity: cells, receptors, and signaling pathways

88%

Blach-Olszewska Z.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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tom 53

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nr 3

245-253

EN

Essential differences between the innate and acquired branches of immunity are described. These differences concern the detection system (receptors and pathogen structures) and the cells engaged in both systems as well as the effectory mechanisms. In contrast to those of the acquired system, receptors of the innate system, which developed during evolution, recognize unchanged structures on large groups of pathogens (e.g. lipopolysaccharide in Gram-negative bacteria). Two lineages, natural killer (NK) and dendritic cells (DCs), play important roles in the innate system. Phenotypic and functional differentiation is observed among NKs and DCs, so each of their sublineages plays a different role in the innate system. Every lineage of cells of the innate immune system express different stimulatory and sometimes also inhibitory receptors on their surfaces (e.g. NK cells). Among the stimulatory are Toll-like receptors (TLRs), mannose and scavenger receptors, and the stimulatory receptors of NK cells. All TLRs show similarity in structure and in the kind of molecules involved in intracellular signaling. The immune reactions of the innate system involve cytokine-dependent resistance of cells against infection with pathogen, production of cytokines (tumor necrosis factor, interferons, interleukins, chemokines) and MHC-independent killing. Although these reactions protect the host from invasion by microorganisms, they can also be responsible for significant tissue damage or may stimulate the development of autoimmunity. Therefore innate immunity must be under rigorous control. The possible regulatory mechanisms of innate immunity are discussed.

5

Opiate abuse, innate immunity, and bacterial infectious diseases

63%

Wang J. , Barke R. A. , Ma J. , Charboneau R. , Roy S.

Archivum Immunologiae et Therapiae Experimentalis

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2008

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tom 56

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nr 5

299-309

EN

The first line of defense against invading bacteria is provided by the innate immune system. Morphine and other opiates can immediately disrupt the body's first line of defense against harmful external bacteria. Opiate, for example morphine, abuse degrades physical and physiologic barriers, and modulates phagocytic cells (macrophages, neutrophils) and, nonspecific cytotoxic T cells (gd T), natural killer cells, and dendritic cells, that are functionally important for carrying out a rapid immune reaction to invading pathogens. In vitro studies with innate immune cells from experimental animals and humans and in vivo studies with animal models have shown that opiate abuse impairs innate immunity and is responsible for increased susceptibility to bacterial infection. However, to better understand the complex interactions between opiates, innate immunity, and bacterial infection and develop novel approaches to treat and even prevent bacterial infection in the opiate-abuse population, there is an urgent need to fill the numerous gaps in our understanding of the cellular and molecular mechanisms by which opiate abuse increases susceptibility to bacterial infection.