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1

The role of dendritic cells in neurodegenerative diseases

100%
Iribarren P., Cui Y.-H., Le Y., Wang J. M.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
|
issue 3
187-196
EN
Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) involved in the induction of adaptive immune responses. The presence of DCs in the central nervous system (CNS) and the active participation of the immune system in a variety of neurodegenerative diseases have been demonstrated. This review will discuss recent findings pertinent to DCs and other antigen presenting cells in CNS in health and disease states.
2

Interleukin 15: Its role in inflammation and immunity

80%
Perera L. P.
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|
vol. 48
|
issue 5
457-464
EN
Interleukin-15 (IL-15) is a 14-15 kDa polypeptide that belongs to the four alpha-helix bundle family of cytokines and was originally discovered due to its T cell proliferative activity. It utilizes the signal transducing b/g polypeptides of the IL-2 receptor complex thus sharing many biological activities with IL-2, in addition to its high affinity private receptor subunit IL-15Ra. Accumulating evidence indicates that the biological relevance of IL-15 may not solely be confined to T lymphocytes, but to a variety of cell populations within the immune system as well as outside the immune system of the host. The expression of both IL-15 and its high affinity receptor component, IL-15Ra are readily demonstrable in a wide variety of tissues and appear to be augmented in response to environmental/stress stimuli and infectious agents. There is increasing evidence to suggest that IL-15 may play an important role in protective immune responses, allograft rejection and the pathogenesis of autoimmune diseases where mononuclear cell infiltration is a hallmark feature. Herein, the effects of IL-15 on cells associated with host defense, immunity and inflammation are reviewed and support a central role for this cytokine in orchestrating multiple aspects of effector functions in immunity and inflammation.
3

The role of the lysophospholipid sphingosine 1-phosphate in immune cell biology

80%
von_ W. H., Zimmermann K., Kleuser B.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
|
issue 4
239-251
EN
Sphingosine 1-phosphate (S1P) has been shown to be a bioactive lipid mediator intimately involved in mediating a variety of immunological processes. In particular, S1P regulates lymphocyte cell trafficking between the lymphatic system and the blood. The lysophospholipid signals mainly through five related G protein-coupled receptor subtypes, termed S1P1 to S1P5. S1P1 seems to play an especially essential role in cell trafficking, as this receptor subtype promotes the egress of T and B cells from secondary lymphatic organs. This S1P1-mediated migratory response is a consequence of different S1P levels in the serum and lymphatic organs. In addition to its direct effects on lymphocyte motility, S1P strengthens cell barrier integrity in sinus-lining endothelial cells, thereby reducing lymphocyte egress out of lymph nodes. Furthermore, S1P modulates cytokine profiles in T and dendritic cells, resulting in an elevated differentiation of T helper-2 cells during the T cell activation process. It is of interest that the mode of molecular action of the novel immunomodulator FTY720 interferes with the signaling of S1P. After phosphorylation, FTY720 shares structural similarity with S1P, but in contrast to the natural ligand, phosphorylated FTY720 induces a prolonged internalization of S1P1, resulting in an impaired S1P-mediated migration of lymphocytes.
4

Immunology of viral co-infections with HIV

80%
Northfield J. W., Harcourt G., Lucas M., Klenerman P.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
|
issue 1
3-12
EN
Increasing clinical evidence is emerging that other persistent viral infections can act as important co-factors affecting the progression of human immunodeficiency virus-1 (HIV-1). It appears that hepatitis C (HCV) and cytomegalovirus (CMV) have a deleterious effect on HIV progression, whereas hepatitis G (GBV-C) benefits HIV-1 progression. At the same time, the aggressive nature of HCV infection in HIV is clearly recognized. Here we discuss this clinical evidence and go on to review scientific work pertaining to these interactions in the context of the known and theoretical immunological effects of these viruses. This is discussed at the level of the generation of adaptive immune responses and their effector functions. It is clear that co-infection with persistent viral infections may pose special problems for the human immune system, as pathogenic effects may not be specific to the actual eliciting virus and can therefore multiply the difficulties faced by host defenses. We also highlight the need for further therapies for HIV/HCV co-infected persons, as this is currently a complex and severe syndrome.
5

Influence of dendritic cells on the in vitro allogeneic cytotoxic reaction of lymphoid cells derived from normal or listeria innocua-infected BALB/c mice

80%
Goscicka T., Walencka M., Fol M., Krupa A., Szeliga J.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
|
issue 6
447-452
EN
The role of lymphoid dendritic cells (DCs) in the development of an allogeneic cytotoxic reaction in vitro was examined. The T+B and T cell subsets originating from the spleens or lymph nodes of normal and Listeria innocua-infected BALB/c mice were used as the effector cells. Their cytotoxicity to 51Cr-labeled C3H fibroblasts was determined after removal of DCs and replacing them again. Moreover, the influence of exogenous mrIL-12 on the potency of DCs in the allogeneic reaction developed in vitro was checked. It was found that the DC-deprived T+B or T subsets of splenocytes, regardless of their origin, exhibited 27-38% lower cytotoxicity than those accompanied by natural DCs. The cytotoxicity of these subsets from normal lymph nodes decreased by 22%, while the activity of bacteria-primed cells dropped by 38%. Replenishing effector cells with isolated DCs restored their cytotoxicity. Pulsation of normal DCs with IL-12 had no effect on the recovery of normal cell cytotoxicity. However, the IL-12-pulsed DCs were able to intensify the cytotoxicity of T+B subsets derived from the spleens or lymph nodes of L. innocua-infected mice. The results suggest that the alloantigen presentation by DCs to cytotoxic lymphocytes also takes place in the reaction developed in vitro, regardless of effector cell origin.
6

Considerations on clinical use of T Cell immunotherapy for cancer

80%
Plautz G. E., Cohen P. A., Shu S.
Archivum Immunologiae et Therapiae Experimentalis
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2003
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vol. 51
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issue 4
245-257
EN
The recognition by effector T lymphocytes of novel antigenic targets on tumor cells is the premise of specific targeted immunotherapy of cancer. With the molecular characterization of peptide epitopes from melanoma antigens, and more recently broadly expressed tumor antigens, there has been considerable enthusiasm for clinical evaluation of peptide tumor vaccines. Immunologic monitoring of vaccinated patients has demonstrated expansion of CD8+ T cells that react with the relevant peptide and, more importantly, with native tumor. In most instances however, vaccine-induced CD8+ T cell responses alone have not been sufficiently robust or sustained to translate into a high percentage of durable clinical responses. Vaccine strategies have also utilized dendritic cells (DCs) that have been modified to present tumor antigens. The superior antigen processing capacity and co-stimulatory function of DC convey a powerful stimulatory signal to both CD4+ and CD8+ T cells. Several strategies are attempting to broaden the immune response beyond single antigens by introducing the entire complement of tumor antigens into DCs. Adoptive immunotherapy is a promising strategy to recover tumor-reactive precursor T cells from patients, stimulate them to induce numerical expansion, and then re-infuse them. Ex vivo manipulation of the tumor-reactive T cells also permits cytotoxic therapy to be administered to the patient without damaging the effector cells. Recently, host lymphodepletion prior to adoptive transfer of effector T cells has resulted in an extremely high and sustained frequency of effectors that has achieved therapeutic efficacy against bulky metastatic disease in a substantial fraction of treated patients.
7

Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis

80%
Smolewska E., Cebula B., Brozik H., Stanczyk J.
Archivum Immunologiae et Therapiae Experimentalis
|
2008
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vol. 56
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issue 4
283-289
EN
Introduction: The pathogenesis of juvenile idiopathic arthritis (JIA) is not fully understood. Recently the present authors described disturbed apoptosis of JIA lymphocytes in both peripheral blood (PB) and synovial fluid (SF) as well as an abnormal distribution of blood dendritic cells (BDCs) between the PB and SF in this disease. Possible relationships between these events during the development of JIA process are assessed here. Materials and Methods: Lymphocyte apoptosis and BDC counts were assessed in the PB and SF of untreated JIA children. Lymphocyte apoptosis was analyzed by the Annexin-V/propydium iodide assay. Total DC (TDC) number was based on the sum of three BDC subpopulations determined using a panel of monoclonal antibodies against BDC antigens (BDCA): myeloid type 1 (mDC1, BDCA-1+/HLA-DR+/CD19?), myeloid type 2 (mDC2, BDCA-3+/HLA-DR+/CD14?), and plasmacytoid (pDC, BDCA-2+/HLA-DR+/CD123+). Cells were enumerated by the flow cytometric ?single-platform' method. The concentration of tumor necrosis factor (TNF)- alpha and the distribution of particular lymphocyte subtypes in both PB and SF were also investigated. Results: There was significant positive correlation between apoptosis of PB lymphocytes and SF TDC count (p=0.002) as well as SF TNF- alpha concentration (p=0.007). SF TNF-alpha levels also correlated with SF TDC count (p=0.003). Moreover, JIA SF was distinctly enriched with CD4+ and CD8+ T lymphocytes and included CD4+/CD25high cells as well. There was significant positive correlation between the number of CD4+/CD25high cells and SF JIA BDC count (p=0.015). Conclusions: These data suggest a possible link between impaired apoptosis of PB/SF lymphocytes and increased recruitment of PB BDCs to SF and other elements of the immune system in JIA, including regulatory CD4+/CD25high cells.
8

Effective tumor immunotherapy: start the engine, release the brakes, step on the gas, ...and get ready to face autoimmunity

80%
Tirapu I., Mazzolini G., Rodriguez-Calvillo M., Arina A., Palencia B., Gabari I., Melero I.
Archivum Immunologiae et Therapiae Experimentalis
|
2002
|
vol. 50
|
issue 1
13-18
EN
Cellular immune responses can destroy cancer cells, achieving the cure of experimental malignancies. An expanding wealth of knowledge on the molecular basis of how to prime and amplify a T cell response has fueled a number of strategies successful at treating established tumors (rather than merely preventing tumor grafting). The most efficacious approaches operate at different stages, including: 1) priming the immune response using tumor antigen-expressing dendritic cells or tumor cells transfected with genes that render them immunogenic, 2) sustaining and amplifying immunity using agonistic monoclonal antibodies against costimulatory molecules or immune-potentiating cytokines, and 3) eliminating mechanisms that self-regulate the strength of the immune response, such as inhibitory receptors or regulatory T cells. A rational combination of such approaches holds great hope for cumulative and synergistic effects, but there is also evidence that they can open the flood-gates for unwanted inflammatory reactions. The next decade can be envisioned as the time when the first reproducibly efficacious combination regimes for cancer immunotherapy will become available and widely used in the clinic, as clinicians learn the best strategies and try to harness their potentially damaging effects.
9

Anti-tumoral capabilities of effector cells after IFN- or CpG-motif treatment of cocultured dendritic cells

80%
Erhardt M., Schmidt-Wolf I. G. H., Sievers E., Frank S., Strehl J., von_ L.-T. M., Gorschluter M.
Archivum Immunologiae et Therapiae Experimentalis
|
2006
|
vol. 54
|
issue 6
403-409
EN
Introduction: Ex vivo expansion of monocyte-derived dendritic cells (mDCs) and subsequent coculture with autologous cytokine-induced killer (CIK) cells is an established system to create specific and non-specific anti-tumoral immunity. mDCs constitute the most frequently applied DC subset in clinical studies. One recently published approach to optimize the immunological functions of the DC/CIK cell system is the replacement of interleukin (IL)-4 by interferon (IFN)-alpha in the maturation process of the DCs. Materials and Methods: The expressions of relevant surface antigens of IL-4-DCs and IFN-alpha DCs by flow cytometry and the anti-tumoral activation of effector cells cocultured with both types of DCs using cytotoxicity assays were compared. In addition, short-term coculture experiments with both types of DCs and IFN-LAK effector cells were performed and compared with standard CIK cell coculture experiments. Results: Regarding the expressions of functionally relevant surface markers, no differences could be detected for CD80, CD83, and HLA-DR between IFN alpha-DCs and IL-4-DCs, whereas the mean fluorescence intensities of CD40, CD86, CD54, and HLA-ABC were decreased and the expression of CD14 was increased for IFN alpha-DCs. Moreover, no enhancement of cytotoxicity of cocultured CIK cells against tumor cell lines (A498 and SW480) was detected by the use of IFN-DCs. Additionally, coculture experiments with IFNgamma-LAK cells were performed and unexpectedly higher lysis rates in comparison with the established IL-4-DC/CIK coculture model was observed. Early incubation of the mDCs with several CpG-ODNs failed to increase the anti-tumoral cytotoxicity of the cocultured IFN-LAK cells. Conclusions: These results demonstrate that in the mDC/CIK cell system, IFN-DCs are not superior in inducing anti-tumoral cytotoxicity and even moderately inferior regarding the expression of functionally relevant surface markers compared with IL-4-DCs.
10

A method for directly determining the number of dendritic cells and for evaluation of their function in small amounts of human peripheral blood

80%
Markowicz S., Skurzak H. M., Walewski J.
Archivum Immunologiae et Therapiae Experimentalis
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2001
|
vol. 49
|
issue 1
51-58
EN
Bone marrow-derived dendritic cells (DC) are highly potent antigen-presenting cells capable of initiating primary responses of naive T lymphocytes to antigen. Studies on DC in disease have been impeded by the lack of a defined method for accurate DC counting and for evaluation of their function in a small amount of blood. In order to detect and enumerate DC in whole peripheral blood preparations, we applied a direct two-color immunofluorescence method. Blood from healthy donors was stained with a mixture of FITC-conjugated monoclonal antibodies (moAbs) recognizing lineage-associated molecules (CD3, CD14, CD16, CD20, CD57) and PE-conjugated anti-HLA-DR moAb. DC were identified as lineage marker negative (lin-), HLA-DR highly positive cells. The mean percentage of these cells present in peripheral blood leucocytes (PBL) was 0.54%, and the mean absolute DC count was 31.4 x 106/l of blood. DC stained directly in whole blood were heterogeneous with regard to their expression of CD2 and CD4 molecules, and did not express CD80 and CD83 molecules. Expression of CD80 and CD83 on DC was induced following a multistep isolation procedure, including overnight culture. We demonstrated a significant primary proliferative response to keyhole limpet hemocyanin (KLH) in cultures of peripheral blood mononuclear cells (PBMNC). Since primary proliferative response to neoantigens is entirely dependent on DC as antigen-presenting cells, the cultures of unseparated PBMNC stimulated with KLH can be used to evaluate DC function in a relatively simple test. This test does not require previous isolation of DC and T lymphocytes and, therefore, can be performed on a small amount of blood. The elaborated flow cytometric method of DC counting in blood and the proliferative test of DC-dependent primary response to neoantigen are currently being applied in an ongoing study on the effect of chemotherapy on DC number and function in cancer patients.
11

The influence of different culture microenvironments on the generation of dendritic cells from non-small-cell lung cancer patients

80%
Krawczyk P., Wojas K., Milanowski J., Rolinski J.
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2007
|
vol. 55
|
issue 6
405-415
EN
Introduction: Monocyte-derived dendritic cells (DCs) are currently under extensive evaluation as cell vaccines for cancer treatment. Many protocols regarding DC generation in vitro with different protein components, especially autologous proteins, have been described. On the other hand, active tumor-derived factors in patients' serum could impair monocytes, which might result in their abrogated differentiation into DCs in vitro. Materials and Methods: Autologous DCs from non-small-cell lung cancer (NSCLC)-bearing patients were generated in different culture microenvironments. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of interleukin-4 and granulocyte-monocyte-stimulating factor with supplementation of 10% autologous serum, 10% allogenic serum, or 2% human albumin. The course of apoptosis, phagocytic ability, and the immunophenotype of the generated DCs were analyzed using flow cytometric methods. Results: After 48 h of culture, we found a lower percentage of CD1a+/CD14+ and a higher percentage of CD1a+/CD14? cells in the culture supplemented with human albumin than in the cultures supplemented with serums. The lowest CD14 antigen expression was found in the human albumin-supplemented 48-h cultures. After 48 h in the cultures carried out with human albumin we found significantly higher percentages of AV+/PI+ cells and AV?/PI+ cells than in cultures supplemented with autologous or allogenic serum. We also noted that the expression of FITC-dextran after 4 and 24 h of incubation was significantly higher in the cultures supplemented with both serums than in the HA-SC. The percentage of semi-mature DCs and of CD83 expression was lowest in the culture supplemented with 2% human albumin. Conclusions: The kind of culture supplementation had a great impact on the apoptosis of cultured PBMCs. It could also influence the yield of monocyte-derived DCs. It was also confirmed that autologous and allogenic serums provide suitable microenvironments for the generation of autologous DCs from NSCLC patients. The choice of culture supplementation for DC generation is still unsolved and further studies should be undertaken
12

DNA viruses and genetic modification of dendritic cells

80%
Jenne L., Steinkasserer A.
|
|
issue 4
273-279
EN
An alternative approach to the use of tumor-peptide-loaded dendritic cells (DC) in immunotherapy would be the use of genetically modified DC using viral vectors expressing tumor-associated antigens (TAA). However, viruses have developed several immune escape mechanisms and, thus, one has to study the interaction between viruses and DC before these viruses can be used as an alternative strategy. Here we report that vaccinia virus (VV) as well as herpes simplex virus type-1 (HSV-1) are able to potently infect monocyte-derived DC, however, this infection leads to the inhibition of the DC-mediated T cell stimulation in vitro.
13

The social life of NK cells

80%
Martin-Fontecha A., Carbone E.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
|
vol. 49
|
issue 1 suppl.
33-40
EN
Natural killer (NK) cells represent a distinct population of lymphocytes that was originally identified by its ability to kill transformed cell lines in vitro. It is now clear that these cells also play an important role in the innate immune response against a variety of pathogens, such as virus, bacteria and parasites. In the past few years, different protocols have been developed to activate NK cells ex vivo, allowing a detailed molecular analysis of the interaction of these cells with their cellular targets. NK activity is regulated by signals generated by both inhibitory and stimulatory receptors expressed by target cells. Indeed, recent results indicate that, while major histocompatibility complex class I molecules (MHC-I) expressed on target cells inhibit NK lytic activity by engaging surface inhibitory receptors, costimulatory molecules such as B7-1, B7-2 and CD40, are able to actively trigger NK activity. This review discusses the most recent findings on the role of costimulation on NK activation and forsees the possible consequences of the interaction between NK cells and dendritic cells (DC) on the development of an adaptive immune response.
14

Role of antigen-presenting cells in innate immune system

80%
Ohteki T., Koyasu S.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
|
vol. 49
|
issue 1 suppl.
47-52
EN
Activation of antigen-presenting cells (APC) and natural killer (NK) cells initiates the production of various proinflammatory cytokines, including interleukin 12 (IL-12), interferon gamma (IFN-) and nitric oxide (NO), which are important in the innate immune response for controlling infection by intracellular pathogens. In this review, we focus on these cytokines produced by APC and summarize the current understanding of how APC functions are regulated by cytokines in innate immunity.
15

Pathogenetic mechanisms of atopic dermatitis

70%
Pastore S., Giustizieri M. L., Mascia F., Giannetti A., Girolomoni G.
|
|
vol. 48
|
issue 5
497-504
EN
Atopic dermatitis (AD) is a chronic inflammatory disease which results from complex interactions between genetic and environmental mechanisms. An altered lipid composition of the stratum corneum is responsible of the xerotic aspect of the skin, and determines a higher permeability to allergens and irritants. Keratinocytes of AD patients exhibit a propensity to an exaggerated production of cytokines and chemokines, a phenomenon that can have a major role in promoting and maintaining inflammation. Specific immune responses against a variety of environmental allergens are also implicated in AD pathogenesis with a bias towards Th2 immune responses. In particular, dendritic cells expressing membrane IgE receptors, play a critical role in the amplification of allergen-specific T cell responses. Cross-linkage of specific IgE receptors on dermal mast cells provokes release and synthesis of a vast series of mediators. Following their recruitment and activation into the skin, eosinophils are also thought to contribute relevantly to tissue damage. Thus, a complex network of cytokines and chemokines contributes to establish a local milieu that favors the permanence of inflammation in AD skin.
16

Biological activity of dendritic cells generated from cord blood CD34+ hematopoietic progenitors in IL-7- and IL-13-conditioned cultures

70%
Mytar B., Stec M., Weglarczyk K., Zembala M.
Archivum Immunologiae et Therapiae Experimentalis
|
2009
|
vol. 59
|
issue 1
67-74
EN
Introduction: Dendritic cells (DCs) are required for initiation of the immune response and may therefore be used for the production of cancer vaccines. As mature DCs (mDCs) are the most potent antigen-presenting cells, there is increasing interest in generating them ex vivo. The present study was designed to obtain mDCs from CD34+ hematopoietic progenitors by culturing them in different media. Materials and Methods: Cord blood CD34+ hematopoietic progenitors were expanded for 7 days in FST medium containing fms-related tyrosine kinase 3 ligand (Flt3-L), stem cell factor (SCF), and thrombopoietin (TPO). Then the cells were divided into three parts and cultured for 21 days in different media: FST medium or FST enriched in interleukin (IL)-3 (FST3 medium) or supplemented with IL-7 and IL-13 (FST713 medium). At the end of culture part of the cells was harvested, counted, and analyzed while the other part was matured with proinflammatory cytokines for 2 days. The cells' phenotypes, ability to induce proliferation of allogeneic lymphocytes in the mixed lymphocyte reaction (allo-MLR), chemotaxis, phagocytosis, and O2? production were determined. Results: The average fold increase of DCs at the end of culture in FST medium was 127, in FST3 1043, and in FST713 71. In comparison with the other media, FST713 medium supported the generation of mDCs that were characterized by higher expressions of CD83, costimulatory molecules, and HLA-DR, enhanced ability to induce allo-MLR and migration to macrophage inflammatory protein (MIP) 3?, poor phagocytosis, and O2? production. Conclusions: This study indicates that FST713 medium allows the generation of limited numbers of more mature DCs, while FST3 medium leads to the production of immature DCs in high numbers.
17

Dendritic cells and their application in cancer immunotherapy - achievements and future prospects

70%
Rossowska J., Pajtasz-Piasecka E.
Postępy Higieny i Medycyny Doświadczalnej
|
2003
|
vol. 57
|
issue 5
501-518
EN
Dendritic cells (DC) are generally believed to play a key role in the initiation of immune response. A potential usefulness of these cells in antitumor immunotherapy is strongly considered in every stage of cancer treatment. Studies on tumor tissue infiltration by immune cells shown, that DC represented only a small percentage of leukocytes. The influence of tumor environment resulted in reduction of DC number, their inability to migrate across endothelial barriers, or impaired maturation and efficiency of tumor antigens presentation. Thus, decreased number of DC in tumors could be associated with a bad prognosis. Many attempts concentrate on the creation of the DC-based vaccines, which would generate strong anticancer cell mediated immunity. They include studies on stage of differentiation of the administered DC; effective way for antigen loading; optimum route and schedule of DC delivery into tumor bearing host; effective vectors for the therapeutic genes; effects of the therapy based on cytokine secreting DC; influence of DC on co-operation between innate and acquired immunity as well as on the generation of specific antitumor response. This review is focused on two important areas aiming for the preparation of DC vaccine for effective stimulation of immune response: - loading of DC with tumor antigens (or other ways of DC preparation to successful antigen presentation) - as an encouraging evidence of therapeutic efficacy, and - genetic modification of DC with cytokines resulting in the stimulation or alteration of the antitumor DC activity - as a promising anticancer strategy.
18

Monocyte-related immunopathologies in trauma patients

70%
Laudanski K., Wyczechowska D.
Archivum Immunologiae et Therapiae Experimentalis
|
2005
|
vol. 53
|
issue 4
321-328
EN
Mechanical trauma is one of the most important causes of morbidity in the developed world. The response of the immune system to mechanical insult is of paramount importance for the patient's recovery. Shortly after trauma, the indiscriminate saystemic inflammatory response syndrome (SIRS) is mediated by circulating monocytes (Ms) and other innate immunity components. Then acquired immunity, limited to the offending pathogen and the site of injury, gradually preponderates. SIRS is followed by the compensatory anti-inflammatory response syndrome (CARS), where the initial inflammatory response is quenched by anti-inflammatory mediators. This precisely regulated process of immune system activation in response to trauma can be easily deviated, resulting in multi-organ failure (MOF) and increased mortality. Excessive activation of inflammatory Ms in the SIRS phase, premature or exorbitant CARS, a predominance of macrophages (Macs) in the blood stream and peripheral tissues, as well as a depletion of dendritic cells are often seen in trauma patients and contribute to the development of MOF. Here we explore several mechanisms of pathological M? activation in patients with severe mechanical traumatic injury without accompanying sepsis.
19

Rethinking globally relevant vaccine strategies to human immunodeficiency virus type-1

61%
Gray C. M., Puren A. J.
|
|
vol. 48
|
issue 4
235-241
EN
According to the latest UNAIDS figures for 1999 there were an estimated 30. 6 million people living with HIV-1, with 16000 new HIV infections per day. The only global strategy of combating new HIV infections is to make a vaccine that is affordable to developing countries, where greater than 90% of new infections occur, and that has enough efficacy to interrupt high rates of transmission. This review critically examines: 1) important immune parameters that should be considered which will allow an understanding of preventative vaccine design and 2) the mechanisms underlying immune destruction during HIV-1 infection that will facilitate design of therapeutic vaccines. A realistic goal of a preventative vaccine is to elicit protective immune responses in vaccinees that would prevent HIV-1 from replicating extensively in the host. Components of protective immunity are thought to include neutralizing antibodies (NAB) and cytotoxic T lymphocytes (CTL). Rethinking vaccine strategies has to take into account that HIV-1 vaccines must elicit primary cellular and humoral immunity via dendritic cell and Langerhan cell priming. It is only under these conditions that boosting immunity with subsequent vaccinations will allow high enough CTL effector cells and NAB titres to impede or to prevent HIV-1 replication. Success of therapeutic vaccine strategies, has to take into consideration the pathology of persistent immune stimulation by chronic HIV-1 infection. To re-stimulate immunity and re-direct immune responses, chronic immune stimulation by HIV-1 has to be alleviated by reducing high levels of viral antigen presentation by suppressing virus with antiretroviral agents. Such treatment courses may only have to be transient, long enough for immunity to respond to an immunogenic stimulus. Short-course drug therapy may then be an affordable option for many countries already carrying a high burden of HIV-1/AIDS.
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