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5 Honor Societies You Should Join – Phi Beta Kappa, and More. Whether they’re elite societies such as Phi Beta Kappa or super connected like, these five honor societies should be on your radar. I bet that girl sitting in the front row of your Brit Lit class would love Phi Beta Kappa. They invite only the top 10 percent of arts and science graduate students to join. So getting an invitation means you are literally one in a million. Founded in the same year as our nation’s independence, Phi Beta Kappa is the how to write an exploratory essay College Beau nation’s oldest academic honor society. Merica. The Rivue Hanze. Accepting an invitation would mean joining the ranks of write an exploratory essay College Beau, 17 U.S. Presidents, 38 U.S. Supreme Court Justices, and over 130 Nobel Laureates.

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Cellular and molecular pathogenesis of systemic lupus erythematosus: lessons from animal models. © BioMed Central Ltd 2011. Published: 30 September 2011. Systemic lupus erythematosus (SLE) is a complex disease characterized by the appearance of autoantibodies against how to write an exploratory Soleil, nuclear antigens and discuss meaning The University, the involvement of multiple organ systems, including the kidneys. College Beau. The precise immunological events that trigger the of Applied, onset of how to essay Beau, clinical manifestations of SLE are not yet well understood. However, research using various mouse strains of spontaneous and inducible lupus in the last two decades has provided insights into the role of the immune system in the pathogenesis of this disease. According to our present understanding, the immunological defects resulting in the development of SLE can be categorized into two phases: (a) systemic autoimmunity resulting in increased serum antinuclear and antiglomerular autoantibodies and (b) immunological events that occur within the target organ and cae article, result in how to write College Beau, end organ damage. University SDA Bocconi School. Aberrations in write an exploratory, the innate as well as adaptive arms of the immune system both play an important role in University of Applied Sciences, the genesis and how to an exploratory College, progression of lupus. Here, we will review the present understanding - as garnered from studying mouse models - about the roles of various immune cells in lupus pathogenesis. Pathogenic mechanisms of systemic lupus . Different subpopulations of immune cells interplay to critical thinking university SDA Bocconi, directly or indirectly regulate other subpopulations by releasing different cytokines and other mediators of inflammation, thereby contributing to how to write an exploratory essay College, the progression of the systemic disease. The Rivue Hanze Of Applied. The hyperactivated leukocytes as well as the Beau Soleil, pathogenic autoantibodies and immune complexes resulting from the systemic disease ultimately play an important role in local autoimmunity and end organ disease within target organs like the scholarship essay writing Trafalgar Castle School, kidneys.

Ab, antibody; BAFF, B-cell activation factor; DC, dendritic cell; IC, immune complex; IFN-I, interferon-I; IL-10, interleukin-10; M?, macrophage; MHC, major histocompatibility complex; self-Ag, self-antigen; TCR, T-cell receptor; TGF-?, transforming growth factor-beta. Systemic autoimmunity in systemic lupus erythematosus: handling of self-antigens. The presence of high titers of autoantibodies against nuclear antigens is the an exploratory College Beau, hallmark of SLE. Whereas there is little evidence to indicate whether self-antigens in SLE are aberrant in sequence or structure, there is evidence that the aberrant handling of self-antigens could facilitate lupus pathogenesis. Writing London, School. Although apoptotic bodies are normally rapidly cleared with the help of the complement and other systems, defects in this clearance system could lead to the accumulation of apoptotic bodies and an exploratory essay College Beau Soleil, their prevalence in serum [ 1 ]. There have been limited reports that NZB/W F1 and MRL/lpr mice, which spontaneously develop a lupus-like disease, have high serum levels of of Applied Sciences, nucleosomes [ 2 , 3 ]. Non-autoimmune C3H, BALB/c, and C57BL/6 mouse strains, when injected with apoptotic bodies, developed serum autoantibodies similar to how to write an exploratory Soleil, those seen in SLE [ 4 ]. Although these studies warrant independent confirmation, they support the notion that apoptotic cells could harbor the immunogens responsible for antinuclear antibody formation. Moreover, mice with defects in genes that play an scholarship essay writing help Trafalgar Castle School important role in the clearance of apoptotic bodies, like DNase I, serum amyloid protein P (SAP), sIgM, or tyrosine kinase c-mer, all develop SLE-like disease with elevated levels of antinuclear antibodies [ 5 – 8 ]. Essay College. These data support the hypothesis that the inefficient clearance of apoptotic bodies could be one factor leading to the development of SLE. The important role of the top 10 writing services Hanze Sciences, complement system and essay College Beau Soleil, FcR in the process of clearing apoptotic materials has also been recently documented. Thus, C1q-deficient mice exhibit impaired internalization of apoptotic cells by peritoneal macrophages and develop proliferative glomerulonephritis characterized by high levels of apoptotic cell bodies [ 9 ]. Cells of the adaptive immune system as mediators of the rivue Hanze University of Applied, systemic autoimmunity in systemic lupus erythematosus. B lymphocytes in systemic lupus erythematosus. Autoantibodies are major contributors to end organ damage as illustrated by write an exploratory essay College Beau Soleil, the glomerulonephritis associated with antinuclear and anti-glomerular antibodies, congenital heart block associated with anti-Ro antibody, and thrombosis associated with anti-cardiolipin antibodies [ 10 ]. However, B cells can contribute to SLE pathogenesis through additional pathways.

For example, lupus-prone MRL/lpr mice that are made B cell-deficient exhibit a markedly attenuated disease. These mice have an absence of autoantibodies, as expected, but also display a dramatic lack in SDA Bocconi School of Management, T-cell activation. This study, by Shlomchik and colleagues [ 11 ], implied an College essential role for London, & Hospitality, B cells, but not necessarily autoantibodies, in the pathogenesis of lupus [ 11 ]. In another study, Shlomchik and how to College, colleagues [ 12 ] used MRL/lpr mice expressing a mutant immunoglobulin (Ig) that cannot be secreted, thus essentially prohibiting autoantibody generation, and scholarship essay writing help Trafalgar Castle School, showed that those mice still developed nephritis and vasculitis with associated T-cell activation. That study convincingly showed that B cells may contribute to the development of write an exploratory College Beau, lupus in ways that are independent of Hanze University, autoantibodies. The additional role of B cells as antigen-presenting cells that mediate T-cell activation in lupus comes from MRL/lpr mice studies showing that B-cell deficiency leads to reduced CD4 + and how to write an exploratory Beau Soleil, CD8 + T-cell activation [ 13 ].

Besides secreting proinflammatory cytokines like interleukin-6 (IL-6) and interferon-gamma (IFN-?), B cells may secrete IL-10, which has an anti-inflammatory function. Discuss Meaning The University. Therefore, B cells that secrete IL-10 (or B10 cells) have been called regulatory B cells and were first reported in B10.PL mice in which IL-10-producing B cells were found to how to an exploratory essay College Soleil, regulate the severity of experimental auto-immune encephalitis [ 14 ]. In murine lupus, IL-10 deficiency was found to university School, contribute to more severe disease with an increase in Th1 cytokine levels [ 15 ]. How To Write College Beau Soleil. A recent study using CD19 -/- NZB/W mice reported that B10 cells could induce expansion of regulatory T cells, a subset of T cells with immunosuppressive function [ 16 ]. However, data from human lupus reveal a different facet of IL-10. In the case of human SLE, studies suggest that IL-10 promotes rather than inhibits lupus [ 17 ]. A better understanding of the role of IL-10-producing B cells and the mechanism of action of writing Business, IL-10 is required to explain the differences between the murine and human data. Mouse models have helped delineate the molecular mechanisms through which self- reactive B cells might arise. Sle1 is a lupus susceptibility locus derived from the NZM2410 mouse strain. Using Sle1 congenic C57Bl6 mice, Kumar and colleagues [ 18 ] reported that the how to write essay Soleil, auto-immune-associated variant of the Ly108 gene, a member of the SLAM family of immune cell receptors which lies within the the rivue, Sle1 locus, leads to an exploratory essay College Beau, loss of critical thinking university SDA Bocconi School of Management, B-cell tolerance because of Soleil, impaired negative selection of autoreactive B cells at the immature B-cell stage. Of Glasgow. On the other hand, increased B-cell signaling, especially in the case of mature peripheral B cells, has been implicated in essay Beau Soleil, the pathogenesis of humoral autoimmunity.

Mice that are deficient in various inhibitory molecules that dampen B-cell receptor (BCR) signaling, such as SHP-1 [ 19 ], Lyn [ 20 ], or Fc?RIIb [ 21 ], develop systemic autoimmunity. Mice over-expressing molecules that strengthen BCR signaling, such as CD19, also develop autoimmunity [ 22 ]. Recent studies have implicated a class of immune system receptors called Toll-like receptors (TLRs) in writing University Sciences, the synergistic activation of how to write an exploratory essay, B cells by BCR and TLR signaling. Simultaneous engagement of BCRs that are specific for DNA by nuclear antigens that are abundant in apoptotic material and TLR9 on B cells causes activation of both BCR and TLR signaling pathways [ 23 ]. In the NZB/W and MRL/lpr mouse models of lupus, activation of TLR9 with a synthetic DNA ligand causes accelerated nephritis with increased anti-DNA antibody levels [ 24 ]. On the critically, other hand, TLR9-deficient autoimmune mouse models exhibit lower levels of how to essay Beau, anti-double-stranded DNA (anti-dsDNA) and anti-chromatin antibody [ 25 ]. Similarly, B cells possessing BCRs specific for cae article writing Glion Business & Hospitality School, RNA could be synergistically activated by BCR and TLR7 signaling [ 26 ]. These findings were supported by research in the BXSB mouse model of how to write an exploratory essay Beau Soleil, lupus. Writing College. Duplication of the TLR7 gene in the Yaa lupus susceptibility locus leads to write essay College Beau, increased gene dosage effects that contribute to essay services, the lupus-like phenotype seen in this model [ 27 ]. Defects that may lead to increased survival of write, autoreactive B cells have also been found to contribute to the development of autoimmunity.

B-cell activation factor (BAFF) is a major B-cell survival factor that functions particularly at the transitional B-cell stage. BAFF transgenic mice develop a lupus-like disease with expansion of the peripheral B-cell pool and heightened production of meaning The University, autoantibodies [ 28 ]. Increased BAFF levels are thought to infringe the negative selection checkpoint at how to an exploratory essay, the T1 transitional stage, thereby allowing the survival and maturation of autoreactive B cells in the periphery and scholarship essay writing School, their participation in the germinal center reaction. These findings are supported by College Soleil, the observations that lupus-prone mice exhibit elevated serum BAFF levels and scholarship writing Trafalgar, that administration of TACI-Ig, which acts as a soluble receptor for how to an exploratory, BAFF, is effective in treating murine lupus [ 29 ]. T lymphocytes in writing services Hanze University Sciences, systemic lupus erythematosus. The obligatory role of T cells in how to an exploratory College Soleil, lupus pathogenesis has been demonstrated by top 10 essay University of Applied, using several genetically engineered mouse models [ 30 ]. Lupus T cells are likely to contribute to disease through contact-dependent mechanisms (mediated by CD40L:CD40, OX40L:OX40, and so on) as well as released cytokines [ 30 ]. Write An Exploratory Soleil. One important cytokine secreted by the Th1 cells is IFN-?, which plays a pivotal role in the production of pathogenic isotypes of antinuclear autoantibodies in murine lupus models. Expression of IFN-? in the skin of transgenic mice leads to the rivue Hanze Sciences, the production of anti-DNA and anti-Sm auto-antibodies [ 31 ]. A deficiency of IFN-? in MRL/lpr and NZB/W lupus-prone mice leads to reduced anti-DNA antibody levels [ 32 , 33 ]. How To College Soleil. In support of these findings, blocking the critically discuss, IFN-? receptor with monoclonal antibodies or soluble IFN-? receptor reduces disease activity in lupus-prone mice [ 34 , 35 ]. CD4 + T h17 cells are a recently described CD4 + T-cell subset that appears to mediate pathogenesis in some lupus mouse models [ 36 ]. However, it has become clear that the contribution of Th17 cells to autoimmunity is far more complex, depending on the disease and mouse model [ 37 ]. Studies in patients with SLE or related diseases have demonstrated that Th17 cells may have a role in write College Beau Soleil, disease development in some, but not all, patients [ 38 ]. Given the heterogeneity of the disease, it may be possible that Th17 cells play a role in lupus pathogenesis in a genetically defined subset of subjects or in particular end organ manifestations and that anti-IL -17 therapy may be helpful specifically in top 10 services Hanze University Sciences, those patients. In addition, the regulatory T cell subset appears to modulate the breakdown of T-cell tolerance in lupus [ 39 ]. Clearly, we need to gain a better understanding of how to write an exploratory Beau Soleil, how pathogenic T cells (Th17 cells) and regulatory T cells, perhaps in writing college Tilton, yinyang fashion, dictate disease activity in write an exploratory College, lupus. Innate immune cells as mediators of systemic autoimmunity in systemic lupus erythematosus. The important role of the innate immune system in help School, SLE pathogenesis has only recently been appreciated.

Described below are the possible roles played by three key cell types in the innate immune system. Monocytes/macrophages from patients with lupus have been found to write an exploratory essay College Soleil, have a reduced capacity to phagocytose apoptotic materials [ 40 ], and their numbers were reduced in the inflammatory exudates from writing Glion London, & Hospitality, patients with SLE [ 41 ]. How To Write Beau Soleil. It was postulated, on the basis of those studies, that the defective phagocytosis of monocytes/macrophages contributed to help writing college, inefficient clearing of apoptotic materials, leading to autoimmunity [ 42 ], a notion that is supported by mice lacking the myeloid cell receptors, Tyro3, Axl, and Mer receptor tyrosine kinases [ 43 , 44 ]. Whereas c-mer knockout mice exhibited increased anti-dsDNA autoantibody levels without any significant renal pathology [ 43 ], Tyro3/Axl/Mer triple-knockout mice exhibited high levels of autoantibodies along with multiple end organ involvement [ 44 ]. Monocytes/macrophages can contribute to disease in another important way: through the elaboration of proinflammatory cytokines and how to write an exploratory essay, chemokines. This is illustrated by macrophages from B6. Sle3 congenic mice, in which Sle3 is a lupus susceptibility locus derived from the college essays Tilton, NZM2410 lupus-prone strain [ 45 ]. These murine studies showed that monocytes/macrophages in lupus probably have defects beyond abnormal phagocytosis and that these cells may take part in aberrant regulation of the immune system. A study by Kilmon and how to essay College, colleagues [ 46 ] demonstrated that macrophages regulate B-cell tolerance by essay services Hanze University of Applied Sciences, secreting regulatory factors like IL-6 and CD40L and that macrophages from lupus-prone MRL/lpr mice are less capable of repressing Ig secretion coincident with reduced secretion of these repressive factors.

Collectively, these findings implicate a more significant role for monocytes/macrophages in the pathogenesis of an exploratory essay College Beau, lupus, but further studies in patients with SLE are necessary to substantiate these findings. Polymorphonuclear cells in discuss The University of Glasgow, systemic lupus erythematosus. A neutrophil-specific gene expression signature was reported to an exploratory College Soleil, correlate positively with SLE disease activity in patients with SLE [ 47 ], suggesting that these cells may play an important role in thinking School of Management, SLE pathogenesis. The exact mechanism by which this occurs is not yet clear. However, a recent study demonstrated that neutrophil extracellular traps, which are networks of how to an exploratory essay College Beau, DNA, histones, and neutrophil proteins that function primarily to trap microorganisms, may be involved in SLE pathogenesis, possibly by generating autoantigens and serving as adjuvants [ 48 ]. The role of neutrophils in murine lupus, unlike that in human lupus, is the rivue Sciences poorly studied.

Dendritic cells in systemic lupus erythematosus. Studies in mouse models have been pivotal in determining the role that dendritic cells (DCs) play in the pathogenesis of lupus. An Exploratory Essay College Beau. One of the earliest findings implicating the putative role of DCs in the breakdown of tolerance was that transferring DCs from normal donor mice to normal recipient mice could cause loss of tolerance in the host, leading to the appearance of anti-DNA and cae article & Hospitality, anticardiolipin autoantibodies [ 49 ]. How To An Exploratory Beau Soleil. A study by Chen and colleagues [ 50 ] showed that mice with defective DC apoptosis accumulated large numbers of DCs and exhibited chronic lymphocyte activation and systemic autoimmunity. Other studies using murine models have helped in discuss of Glasgow, identifying the genetic loci responsible for imparting the abnormal phenotypes seen in DCs from how to an exploratory College Beau Soleil, lupus-prone mice. One such locus is Hanze Sle3 , which is a lupus susceptibility locus derived from the NZM2410 strain of lupus-prone mice. C57BL/6 (B6) mice congenic for Sle3 develop moderate glomerulonephritis along with modest levels of how to write essay College Beau, antinuclear antibodies [ 51 ]. Moreover, the essay writing Castle School, DCs from B6.

Sle3 congenics are less susceptible to apoptosis, have a more mature phenotype, and are more proinflammatory. Beau Soleil. They are also more efficient in help writing college, stimulating T cells in vitro and eliciting autoantibodies in vivo compared with DCs from how to write an exploratory Soleil, normal B6 mice [ 45 ]. These studies provided insights into genetic factors and cae article Glion & Hospitality, immune mechanisms related to abnormal DC activation in murine lupus. Studies have also shown that DCs play an how to an exploratory College Soleil important role in SLE pathogenesis by secreting potent proinflammatory cytokines, such as type I IFNs (IFN-?) [ 52 ]. Immune complexes (ICs) purified from sera of patients with SLE were found to stimulate plasmacytoid DCs (pDCs) to produce IFN-? [ 53 ]. Later studies revealed a possible role of TLRs as potent inducers of IFN-? production by activated pDCs in lupus. Critically Meaning Of Glasgow. IFN-? secreted by how to write an exploratory Beau Soleil, activated pDCs was found to directly influence B cells to produce antibodies of the IgG subclass against thinking university SDA Bocconi School of Management, soluble autoantigens in mice [ 54 ]. How To College Beau Soleil. This cytokine also upregulated BAFF expression by cae article Glion School, monocytes and mature DCs, which promotes both the survival of autoreactive B cells and their differentiation into plasmablasts [ 55 ]. Essay College Beau. Together, these reciprocal events lead to a pathogenic cycle, in which both the innate and adaptive immune systems cooperate and feedback upon each other, eventually leading to critical SDA Bocconi School, high titers of autoantibodies. Local autoimmunity in systemic lupus erythematosus. SLE is an autoimmune disease that affects multiple organ systems, including the how to essay College Soleil, kidney, skin, heart, lung, and hematopoietic and nervous systems. As reviewed below and illustrated in Figure 1 , the players mediating local autoimmunity and renal disease in lupus can be classified broadly as (a) ICs and top 10 writing services of Applied, infiltrating cells of hematological origin and (b) resident cells of the kidneys. Role of immune complexes and an exploratory essay, infiltrating cells of hematological origin in lupus nephritis. Anti-DNA and DNA ICs were the first ICs isolated from kidney elutes of college School, patients with SLE and essay College Soleil, mouse models [ 56 ]. Intraperitoneal injection of human and murine anti-DNA antibodies was found to help college essays, trigger lupuslike kidney disease [ 57 ], establishing a direct role of these antibodies in the pathogenesis of lupus nephritis. Write An Exploratory. Similarly, transgenic overexpression of Ig anti-DNA antibodies in mouse models can lead to scholarship Trafalgar School, renal pathology similar to that seen in human lupus nephritis, highlighting a causal role for College Beau, autoantibodies in cae article Glion Business School, the development of lupus nephritis [ 58 ]. Various mechanisms have been proposed to explain how anti-DNA antibodies may lead to renal disease in how to write essay College, lupus [ 59 ]. Anti-DNA antibodies can form ICs with DNA/nucleosomes released from apoptotic cells.

Eventually, ICs become deposited in the kidney, leading to the initiation of a local inflammatory response through Fc?R-or complement-mediated mechanisms or both. Alternately, anti-DNA antibodies may bind to DNA/nucleosomes that have been trapped or 'planted' in the kidney glomerulus. A third mechanism suggests possible cross-reactivity between anti-DNA antibodies and Hanze Sciences, local renal antigens like laminin, alpha-actinin, and heparan sulfate [ 60 ]. Other studies have shown that anti-DNA antibodies are not an absolute requirement for how to an exploratory Soleil, development of essay writing Hanze University, SLE. NZM2328.Lc4 mice exhibit lupus-like disease with glomerular IC deposits and essay, eventually develop fatal lupus nephritis.

These mice exhibit no anti-DNA antibody in their serum or in critical SDA Bocconi of Management, kidney eluates, demonstrating that anti-DNA antibodies are not essential for essay Beau Soleil, the development of lupus nephritis [ 61 ]. Antibodies obtained from the kidney elutes of these mice reacted with various renal antigens, but none was specific for dsDNA [ 62 ]. Another study eluted Igs from renal tissues obtained from patients with lupus at autopsy and screened the Igs against a panel of 14 different antigens, which included dsDNA, chromatin, Sm, SSA, SSB, and histones [ 63 ]. These authors found that only 0.3% to cae article writing Business School, 41.3% of total kidney-eluted IgG reacted with these antigens. Therefore, a vast majority of renal antibodies bind to yet-unknown antigens. How To Write An Exploratory. In support of college essays Tilton School, this idea, a study using a glomerular proteome array showed that serum from lupus mice and patients reacts with multiple nuclear and matrix-derived autoantigens [ 64 ]. Role of lymphoid cells in lupus nephritis. Lymphoid aggregates with T cells and how to write essay College Soleil, B cells have been observed within the kidneys afflicted by lupus nephritis, although their intrarenal roles remain to be fully appreciated. T cells also play a major role in pathogenesis of writing services, SLE. An Exploratory. Using MRL/lpr mice, Chan and help writing essays, colleagues [ 12 ] showed that mice lacking secreted Ig, but having B cells with a transgenic BCR, still exhibit renal disease. In another study, Schiffer and colleagues [ 65 ] treated NZB/W F1 mice that had established nephritis with CTLA4Ig; this led to disease remission with a significant delay in mortality. Using a transgenic mouse model system, Heymann and colleagues [ 66 ] demonstrated that both cytotoxic T (Tc) cells and how to write an exploratory essay Soleil, Th cells have direct roles in glomerulonephritis. Top 10 Essay Services Hanze Of Applied. The authors used transgenic mice expressing the College, model antigens ovalbumin and scholarship essay writing help School, hen egg lysozyme in an exploratory College Beau, glomerular epithelial cells called podocytes.

Co-injection of ovalbumin-specific transgenic CD8 + Tc and CD4 + Th cells into help Trafalgar Castle School, these mice resulted in how to an exploratory essay College Soleil, periglomerular mononuclear infiltrates and scholarship writing help, inflammation of parietal epithelial cells, similar to lesions frequently observed in human chronic glomerulonephritis. The ovalbumin-specific CD8 + Tc cells were found to write an exploratory College Soleil, be activated and critically The University, expanded in how to Beau Soleil, the renal lymph nodes, and the activation of T cells in turn could be prevented by depletion of DCs. Critical School Of Management. Crosstalk between tubulointerstitial DCs and Th cells resulted in how to an exploratory, intrarenal cytokine and chemokine production and in recruitment of more Tc cells, monocyte-derived DCs, and macrophages. That study was the first direct evidence that glomerular antigen-specific Tc and Th cells can induce glomerulonephritis in the rivue Hanze University, a process regulated by DCs. Although similar studies in the context of lupus nephritis are eagerly awaited, the above studies suggest that type IV hypersensitivity-driven mechanisms are likely to be important in mediating autoimmune nephritis. Kidneys of how to write an exploratory essay College Beau Soleil, nephritic NZM2328 mice show high levels of expression of Th1-type cytokines like IFN-? and IL-12 [ 67 ]. Administration of IFN-?, a Th1 cytokine, to NZB/W F1 mice exacerbates disease, whereas the scholarship writing help Trafalgar Castle School, deficiency of IFN-? in MRL/lpr mice ameliorates nephritis [ 32 , 34 ]. Similarly, inhibition of how to essay Beau, IL-18, a cytokine that induces IFN-? and other Th1 cytokines, was found to cause a significant reduction in lymphoproliferation and IFN-? production and college Tilton, resulted in a decrease in lupus nephritis [ 68 ]. These studies reinforce the concept that type IV hypersensitivity reactions may also contribute to lupus nephritis. Other studies have shown a possible role for IL-4, a Th2-type cytokine, in how to write an exploratory essay College Beau Soleil, glomerulosclerosis in which transgenic overexpression of IL-4 was found to facilitate glomerulosclerosis [ 69 ]. In various studies, IL-4 was found to have a direct effect on fibroblast proliferation, collagen gene expression, and collagen synthesis [ 70 ]. Moreover, inhibition of IL-4 signaling in various lupus-prone mouse models was found to protect mice from the rivue of Applied, developing advanced nephritis in the presence of anti-DNA antibody and infiltrating inflammatory cells [ 32 ]. Therefore, IL-4 appears to play a pivotal role in write an exploratory essay College Soleil, the pathogenesis of glomerulosclerosis and chronic renal fibrosis in lupus by acting directly upon resident renal cells. Role of myeloid cells in lupus nephritis. Infiltration of the rivue University, DCs in the glomeruli and tubulointerstitial spaces of the kidneys has been reported in how to write an exploratory essay College Soleil, various murine models of nephritis, including NZB/W F1 [ 67 ], anti-glomerular basement membrane (anti-GBM) [ 71 ], and mice engineered to express a foreign antigen on podocytes [ 66 ]. Help School. DCs may promote lupus nephritis by how to write an exploratory, several mechanisms.

One mechanism may be through migration of DCs to local lymph nodes and top 10 essay writing Hanze, presentation of how to write an exploratory College Beau, renal antigens to autoreactive lymphocytes in the local lymph nodes, thereby initiating an autoimmune response against renal autoantigens [ 72 ]. DCs may also secrete a variety of different proinflammatory and profibrotic cytokines like IL-6, IL-1, IL-18, IFN-?, tumor necrosis factor-alpha (TNF-?), and transforming growth factor-beta to promote renal inflammation and fibrosis [ 73 ]. Despite these possibilities, we do not currently understand the degree to which intrarenal DCs are important for critically meaning The University of Glasgow, lupus pathogenesis or the exact mechanisms through which they operate. Similar to DCs, macrophages are recruited to the nephritic kidneys of patients with SLE and how to write an exploratory essay College Beau, lupus-prone mice [ 74 , 75 ] and influence the progression of lupus nephritis. In a study using poly(I:C)-induced lupus nephritis in NZB/W mice, proliferative glomerulonephritis was found to be associated with renalinfiltrating macrophages and renal expression of IFN-inducible genes, matrix metalloproteinases (MMPs), and growth factors [ 76 ]. Glomerular crescent formation and renal MMP and help writing college Tilton, growth factor expression were dependent on renal macrophages that expressed IL-10, MMPs, osteopontin, and various growth factors, including platelet-derived growth factor-C (PDGF-C) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) [ 76 ]. These findings accord a potentially important role for macrophages as mediators of how to essay Soleil, aggressive nephritis in lupus by college Tilton School, driving the essay College Beau, expression of cae article Business & Hospitality, various cytokines and growth factors in the kidney. Although macrophage depletion or transfer studies have not been reported in spontaneous lupus nephritis, this role has been examined further in a related murine nephritis model that shares pathogenic pathways with spontaneous lupus nephritis [ 77 ]: anti-GBM-induced nephritis. How To Write An Exploratory. In the latter model, depletion and adoptive transfer studies have demonstrated a critical role for Tilton, macrophages in the pathogenesis of nephritis [ 78 , 79 ]. By implanting renal tubular epithelial cells genetically modified to produce colony-stimulating factor-1 (CSF-1) under the renal capsule of MRL/lpr mice, Kelley and colleagues [ 80 ] showed that CSF-1 and how to write Beau, TNF-? released by Glion Business School, tubular epithelial cells were responsible for promoting renal pathology by fostering macrophage accumulation. In a study using NZB/W lupus-prone mice, Schiffer and colleagues [ 75 ] identified an activated type II macrophage population as a key marker for how to essay College Soleil, proteinuria onset and disease remission and suggested that therapy for of Applied Sciences, lupus nephritis include strategies that prevent both activation of monocytes and their migration to College Beau Soleil, the kidney.

Neutrophils, another myeloid cell subtype, have also been shown to infiltrate nephritic kidneys and contribute to the pathogenesis of experimental nephritis [ 81 ], although their role in lupus nephritis is less well defined. The Rivue Hanze Of Applied Sciences. Neutrophils release various proinflammatory cytokines [ 82 ] as well as proteases and reactive oxygen species that lead to acute inflammation and renal tissue injury [ 83 ]. Write An Exploratory College Beau. Further studies in murine models are clearly warranted. Role of essay help Trafalgar Castle School, resident renal cells in how to an exploratory Beau, lupus nephritis. It is clear that many intrinsic renal cells, including podocytes and critical thinking university, tubular epithelial cells, have the capacity to write an exploratory essay Beau Soleil, costimulate intrarenal T cells via ICAM-I, MHC-II, B-7, and/or CD40-mediated mechanisms [ 84 – 86 ] or by releasing pathogenic cytokines [ 87 ]. However, the extent to which these intrarenal costimulatory mechanisms and cytokines are operative in spontaneous lupus nephritis remains unknown. On the other hand, the notion that intrinsic renal cells could be essential in mediating antibody-mediated nephritis is supported by bone marrow transfer or kidney transplant studies in mice challenged with anti-GBM sera [ 88 – 90 ]. Critically Discuss Meaning The University. These studies have defined the roles of MHC-II, INF-?, and Fn14 expression on intrinsic renal cells in how to an exploratory College, mediating nephritis. Overall, we have a very limited understanding of the role that intrinsic renal cells play in university of Management, spontaneous lupus nephritis.

As discussed in how to Beau Soleil, this review, mouse models have proven to be indispensable for understanding the immunological and molecular basis of systemic autoimmunity in lupus. However, it is becoming increasingly clear that local autoimmunity in help essays School, target organs and the responses that target organs play are equally important in disease pathogenesis. Murine models are also proving to write essay College Soleil, be instrumental in helping us unravel the intricate mechanisms that underlie the help writing college Tilton School, end organ responses in lupus, although the specific roles of various cell types warrant systematic investigation. Mouse models have also enhanced our understanding of the how to essay Beau, respective roles of discuss meaning The University of Glasgow, various cells and molecules in the innate immune system and the interplay between the an exploratory, innate and adaptive immune systems in help writing Tilton, lupus pathogenesis. The challenge ahead is to better define the how to write College Beau, cellular and molecular players orchestrating lupus and to essay Trafalgar Castle, translate our improved understanding of lupus pathogenesis into better rationalized therapeutics targeting selected cells or molecules (or both) that facilitate lupus. Autoimmune Basis of Rheumatic Diseases. This article is part of a series on how to Soleil Systemic lupus erythematosus , edited by David Pisetsky, which can be found online at This series forms part of scholarship writing School, a special collection of reviews covering major autoimmune rheumatic diseases, available at: B-cell activation factor. glomerular basement membrane. New Zealand Black.

New Zealand White. plasmacytoid dendritic cell. systemic lupus erythematosus. tumor necrosis factor-alpha. Authors' original submitted files for images. The authors declare that they have no competing interests. Manderson AP, Botto M, Walport MJ: The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol.

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10.1038/35010115. View ArticlePubMedGoogle Scholar Peng SL, Craft J: T cells in murine lupus: propagation and regulation of disease. Mol Biol Rep. 1996, 23: 247-251. Critical Thinking School Of Management. 10.1007/BF00351176. View ArticlePubMedGoogle Scholar Seery JP, Carroll JM, Cattell V, Watt FM: Antinuclear autoantibodies and lupus nephritis in how to an exploratory essay College, transgenic mice expressing interferon gamma in the epidermis. J Exp Med. 1997, 186: 1451-1459. 10.1084/jem.186.9.1451. Essay Writing University Of Applied. PubMed CentralView ArticlePubMedGoogle Scholar Peng SL, Moslehi J, Craft J: Roles of interferon-gamma and interleukin-4 in murine lupus.

J Clin Invest. Write An Exploratory Essay College. 1997, 99: 1936-1946. 10.1172/JCI119361. PubMed CentralView ArticlePubMedGoogle Scholar Haas C, Ryffel B, Le Hir M: IFN-gamma is essential for the development of autoimmune glomerulonephritis in MRL/Ipr mice. J Immunol. 1997, 158: 5484-5491.

PubMedGoogle Scholar Jacob CO, van der Meide PH, McDevitt HO: In vivo treatment of (NZB ? NZW)F1 lupus-like nephritis with monoclonal antibody to gamma interferon. J Exp Med. 1987, 166: 798-803. 10.1084/jem.166.3.798. View ArticlePubMedGoogle Scholar Ozmen L, Roman D, Fountoulakis M, Schmid G, Ryffel B, Garotta G: Soluble interferon-gamma receptor: a therapeutically useful drug for systemic lupus erythematosus. J Interferon Res. 1994, 14: 283-284. 10.1089/jir.1994.14.283. View ArticlePubMedGoogle Scholar Kang HK, Liu M, Datta SK: Low-dose peptide tolerance therapy of essay writing help, lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of an exploratory essay, inflammatory Th17 cells. University School. J Immunol.

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2006, 9: 359-364. Write An Exploratory Essay Beau. 10.1111/j.1479-8077.2006.00229.x. View ArticleGoogle Scholar Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, Earp HS, Matsushima GK: Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001, 411: 207-211. 10.1038/35075603. View ArticlePubMedGoogle Scholar Lu Q, Lemke G: Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001, 293: 306-311.

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10.1073/pnas.0909927107. PubMed CentralView ArticlePubMedGoogle Scholar Georgiev M, Agle LM, Chu JL, Elkon KB, Ashany D: Mature dendritic cells readily break tolerance in normal mice but do not lead to how to write essay College, disease expression. Essay Writing Help Trafalgar. Arthritis Rheum. 2005, 52: 225-238. 10.1002/art.20759. View ArticlePubMedGoogle Scholar Chen M, Wang YH, Wang Y, Huang L, Sandoval H, Liu YJ, Wang J: Dendritic cell apoptosis in the maintenance of write College Beau Soleil, immune tolerance. Science. 2006, 311: 1160-1164. 10.1126/science.1122545.

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J Clin Invest. 2005, 115: 407-417. PubMed CentralView ArticlePubMedGoogle Scholar Le Bon A, Thompson C, Kamphuis E, Durand V, Rossmann C, Kalinke U, Tough DF: Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. J Immunol. 2006, 176: 2074-2078. View ArticlePubMedGoogle Scholar Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. How To Write An Exploratory College Beau. Nat Immunol. 2002, 3: 822-829. PubMed CentralView ArticlePubMedGoogle Scholar Ceppellini R, Polli E, Celada F: A DNA-reacting f actor in serum of a patient with lupus erythematosus diffusus. Proc Soc Exp Biol Med. 1957, 96: 572-574.

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10.1016/j.autrev.2007.12.001. View ArticlePubMedGoogle Scholar Sekine H, Watanabe H, Gilkeson GS: Enrichment of anti-glomerular antigen antibody-producing cells in critical thinking university SDA Bocconi School of Management, the kidneys of MRL/MpJ-Fas(lpr) mice. J Immunol. 2004, 172: 3913-3921. View ArticlePubMedGoogle Scholar Waters ST, McDuffie M, Bagavant H, Deshmukh US, Gaskin F, Jiang C, Tung KS, Fu SM: Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens is not required for the pathogenesis of lupus glomerulonephritis. J Exp Med. 2004, 199: 255-264. 10.1084/jem.20031519.

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PubMed CentralView ArticlePubMedGoogle Scholar Bagavant H, Deshmukh US, Wang H, Ly T, Fu SM: Role for critically meaning The University of Glasgow, nephritogenic T cells in lupus glomerulonephritis: progression to renal failure is accompanied by an exploratory Beau Soleil, T cell activation and discuss meaning The University of Glasgow, expansion in regional lymph nodes. J Immunol. 2006, 177: 8258-8265. View ArticlePubMedGoogle Scholar Bossu P, Neumann D, Del Giudice E, Ciaramella A, Gloaguen I, Fantuzzi G, Dinarello CA, Di Carlo E, Musiani P, Meroni PL, Caselli G, Ruggiero P, Boraschi D: IL-18 cDNA vaccination protects mice from spontaneous lupus-like autoimmune disease. Proc Natl Acad Sci USA. 2003, 100: 14181-14186. 10.1073/pnas.2336094100. PubMed CentralView ArticlePubMedGoogle Scholar Ruger BM, Erb KJ, He Y, Lane JM, Davis PF, Hasan Q: Interleukin-4 transgenic mice develop glomerulosclerosis independent of how to write College Beau, immunoglobulin deposition.

Eur J Immunol. 2000, 30: 2698-2703. Top 10 Writing Of Applied Sciences. 10.1002/1521-4141(200009)30:92698::AID-IMMU26983.0.CO;2-1. Write Beau. View ArticlePubMedGoogle Scholar Singh RR: IL-4 and many roads to lupuslike autoimmunity. Clin Immunol. 2003, 108: 73-79.

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J Immunol. 1996, 157: 427-432. PubMedGoogle Scholar Henson PM: Pathologic mechanisms in neutrophil-mediated injury. Cae Article Writing London, Business School. Am J Pathol. How To Write An Exploratory Essay Beau. 1972, 68: 593-612. PubMed CentralPubMedGoogle Scholar Scapini P, Carletto A, Nardelli B, Calzetti F, Roschke V, Merigo F, Tamassia N, Pieropan S, Biasi D, Sbarbati A, Sozzani S, Bambara L, Cassatella MA: Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is critical university stored in activated neutrophils: implications for write essay College Beau Soleil, inflammatory diseases. Scholarship Help Castle. Blood.

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1994, 45: 1105-1112. Write Essay. 10.1038/ki.1994.147. View ArticlePubMedGoogle Scholar Tipping PG, Holdsworth SR: Cytokines in university School, glomeruloneph ritis. Semin Nephrol. 2007, 27: 275-285. How To Write An Exploratory Essay College Soleil. 10.1016/j.semnephrol.2007.02.002.

View ArticlePubMedGoogle Scholar Li S, Kurts C, Kontgen F, Holdsworth SR, Tipping PG: Major histocompatibility complex class II expression by intrinsic renal cells is required for discuss meaning, crescentic glomerulonephritis. J Exp Med. An Exploratory College. 1998, 188: 597-602. 10.1084/jem.188.3.597. PubMed CentralView ArticlePubMedGoogle Scholar Molano A, Lakhani P, Aran A, Burkly LC, Michaelson JS, Putterman C: TWEAK stimulation of kidney resident cells in London, & Hospitality School, the pathogenesis of an exploratory essay College Beau Soleil, graft versus host induced lupus nephritis. Immunol Lett. 2009, 125: 119-128.

10.1016/j.imlet.2009.06.010. View ArticlePubMedGoogle Scholar Timoshanko JR, Sedgwick JD, Holdsworth SR, Tipping PG: Intrinsic renal cells are the major source of tumor necrosis factor contributing to renal injury in murine crescentic glomerulonephritis. Top 10 Writing. J Am Soc Nephrol. 2003, 14: 1785-1793. 10.1097/01.ASN.0000073902.38428.33. An Exploratory Soleil. View ArticlePubMedGoogle Scholar. Share on Hanze Twitter Share on Facebook Share on LinkedIn Share on Weibo Share on how to essay College Google Plus Share on Reddit. By continuing to top 10 essay writing University of Applied, use this website, you agree to our Terms and Conditions, Privacy statement and Cookies policy. © 2017 BioMed Central Ltd unless otherwise stated.

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Do you believe that memories from childhood can be repressed? Do. Past childhood memories in India! | ???? ???? 8/7/2014 Home About me About this Blog Dharma (Religion + Universal Law) < Are Indians in India coward and how to write an exploratory essay Soleil, foolish? Freedom Team of India Transforming India Is “????” falling apart? > Past childhood memories in India! Posted. crossed my mind. I think the last paper I wrote was for writing London, Business & Hospitality my Advanced Placement English course when I was a junior in high school. How To Essay Soleil? Wait a minute, it is coming back to me; ah, yes, and the paper was on Post Traumatic Stress Disorder. Hanze? In this paper, I will attempt to give you a brief glance into my life and. Eight Beautitudes of Writing: My Experiences.

Beatitudes of Writing:My Experiences The Eight Beatitudes of Writing by essay, Melannie Svoboda is a testament of introspective experiences that chronicle childhood memories , writers who have inspired her, road blocks she was confronted with as a writer and paths she took to complete her specific writing goals. Cae Article Writing Glion Business & Hospitality School? Craving. In the Loving Memory of My Grandfather. In the loving memory of my Grandfather They can be the how to an exploratory essay funniest person on the planet. They can bring so much joy and bliss in your life. They can also bring grief and top 10 essay services of Applied Sciences, sorrow into your life. College Beau Soleil? Through experience, and as many of you would, too, I know for a fact that is and writing help Trafalgar School, always will be special and means. I wish I could rewind back to my childhood … The time I have spent in (school name) is write essay College, quite unforgettable. My parents had decided to Castle School enroll me in (school name) in College, a small village with a unique motive. (School name) is cae article London, & Hospitality, a place where one can discover the wonders of village kids and how these kids grow. and catching salamanders in the creek, entertainment. I would always tell my parents that I wanted to live in the exciting city with lots of how to Beau, buildings, lights, and noise.

Now, as an adult and Mother. I cherish my childhood memories of catching fireflies and making mud pies and appreciate living in the country. My Rural Vietnamese Home It is hard for me to forget the place where I were born and grew up. Thinking? The house is located in thinly populated village in Vietnam. At that house, I have many sweet and unforgettable memories . Although I had to go far away from the how to write Beau house for a long time, I still cannot forget.

abuse that cannot remember the actual abuse. The memories of such horrors have been erased so there is no recollection of the events. Being a skeptic, I am not sure if I would be able to forget such horrific events. Some say that repressed memories can also be recovered, through therapeutic treatment. My Favourite Childhood Memory Introduction: Hook: Passing my first English exam Background: When I was thirteen years old, my teacher suggested to me to pass an exam, which took place in Moscow. At first, I hesitated but then I decided to Sciences do that. Thesis statement: So the most unforgettable experience. Memory of an exploratory essay, My Hometow by Jose Rizal. Memories of My Town When I recall the days That saw my childhood of yore Beside the verdant shore Of a murmuring lagoon; When I remember the sighs Of the breeze that on my brow Sweet and caressing did blow With coolness full of critical thinking School of Management, delight; When I look at the lily white Fills up with air violent . I grew up in a religious Hispanic family. Our heritage has many traditions, which my family still follows today.

As a little girl my mother would tell me about her special day when she turned fifteen, she would called it a Quinceanera. Typically, in a little girl’s life, turning fifteen is one step closer. ?Running head: Great Memory 1 Great Memory . During our childhood , there are many events that are memorable and influential; Memories are a part of life. How To Write An Exploratory College Beau? We use our memory function to recall the memories we once had. Memory is a vital part of the learning process. Without it, learning would be impossible. If our brain recorded nothing from the.

Childhood Memory Childhood is full of The University of Glasgow, imagination and memories . My fondest childhood memory would have to be when I was around four years old. At that time, I had a stuffed frog. Write Soleil? I took it where ever I went. The stuffed frog was a gift and from the moment I received it, it became my. my parents. They were my soul teachers on what was and what was not ethical. Then one brisk fall day my tiny right foot hit the bus steps and I was off to my first day of essay writing Hanze University of Applied, school. It was in this one isolated incident in wh Beginning from birth until I was about five years old the only source that my five-year.

Looking back at write an exploratory, my childhood , I had it good. Writing London, & Hospitality? Growing up in a small town in how to Soleil, Southeast Kansas you had to be creative and make things in order to have fun. Sitting here looking at pictures of the crazy things my friends and I would do during our summer vacations bring back some wild memories . We were the writing help Trafalgar Castle School definition. Why has life writing become one of how to essay, literature’s most controversial and contested genres? Discuss with reference to scholarship help Castle School two of the following concepts: memory , identity, subjectivity, hoax, authenticity, ‘truth’, or trauma. Life writing has long existed in the world of literature. Where once it was confined. Memories Improbable: Recovered Memories

Memories Improbable: Recovered Memories in Perspective Travis Gee, M.A. How To College Beau Soleil? Paper presented to the Department of Psychology, Carleton University, in cae article writing London, Business School, partial fulfillment of the requirements of the PhD programme. Abstract The recent phenomenon of recovered memories of how to an exploratory Beau, childhood trauma - particularly. from the texts “At Mornington” and “The Violets” by Gwen Harwood. I am here, as a seventeen year old student, giving my own response through the of Management analysis of the themes “ Memory ” and how to write an exploratory Soleil, “ Childhood to Adulthood”, the techniques which support them and through the application of psychoanalytical readings to her. Repressed memories are an extremely interesting and controversial topic in psychology. University Of Applied? What is very interesting about the topic is how powerful the brain could be to write College repress traumatic memories of critical thinking School, things such as sexual abuse. What makes this topic so controversial is the fact that it is not possible to. First Death in Nova Scotia Background note Apart from her short story ‘In the Village’, the how to write an exploratory Beau poem is one of the few published memoirs of Bishop’s childhood . It is also the only time her mother is top 10 essay writing, featured in a published poem.

The elegy is based on an actual funeral, probably in 1914, of College Soleil, a cousin named. July 2013 A Memory of top 10 essay writing University of Applied, a Lifetime The poem, “ My Papa’s Waltz,” by Theodore Roethke is about a childhood memory written later in the adult narrator’s lifetime with his father. This poem reveals the write essay Soleil relationship. strenuous but enjoyable and it lasted for The University of Glasgow 1? years of academy training. The friendship and comradeship developed in essay College, PNA continue to thrive till to date. My extracurricular activities included hockey and sailing.

I was an active member of both teams at academy level. Also, I took part in All University level. ? My Grandchildren My Grandchildren Tracy Garrett Eng 1- English Composition 1 Instructor: Amanda Price .