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Immune Attack (immune + attack)
Selected AbstractsApoptosis in hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 5 2003J. Kountouras Summary. The apoptotic process appears to be a host defence mechanism against viral infections and tumourigenesis. However, many viral genomes encode proteins, which repress apoptosis so as to escape from immune attack by the host. Therefore, virus,host interactions may determine viral persistence, extent and severity of liver inflammation and possibly viral hepatocarcinogenesis. Apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C. Pathomorphologic features of increased apoptosis include shrinkage and fragmentation of nuclei/cytoplasm in piecemeal necrosis areas, acidophilic bodies, and focal cell dropout in the liver lobule. The hepatitis C virus (HCV) core protein exhibits both proapoptotic or antiapoptotic actions. Modulation of apoptosis may involve binding of HCV core protein to the intracellular signal transducing portion of death receptors and displacement of signalling molecules. Apoptosis may occur in the absence of significant transaminase elevation, thereby explaining the lack of correlation between biochemical activity and liver cell histological injury. Monitoring caspase activation might provide a reliable tool to estimate the efficacy of HCV therapy, and might open challenging therapeutic strategies in HCV infection. The antiviral effect of interferon may be mediated through induction of apoptosis. Lastly, administration of the antiapoptotic ursodeoxycholic acid in HCV infection is compatible with the notion that apoptosis may represent a mechanism for viral shedding rather than for viral elimination, thereby raising the concept that inhibition of apoptosis could ameliorate hepatitis C. [source] Immune manipulation of advanced breast cancer: An interpretative model of the relationship between immune system and tumor cell biologyMEDICINAL RESEARCH REVIEWS, Issue 3 2009Andrea Nicolini Abstract This review summarizes some recent clinical immunological approaches with cytokines and/or antibodies for therapy of advanced breast cancer. It considers the recent advances in genetics and molecular tumor biology related to impaired immunosurveillance involving cytokines and growth factors to explain clinical results. Evasion of the host immune attack might be induced by the following groups of mechanisms: (a) tumor dependent (genomic instability, HLA class I antigen abnormalities, upregulation of fetal type nonclassical HLA class I molecules, epitope immunodominance, apoptosis inhibition by defective death receptor signaling, apoptosis of activated T cells, tumor cannibalism and constitutive activation of signal transducer, and activator of transcription-3 (Stat 3) and nuclear factor-,B (NF-kB) signaling); (b) host dependent (CD4+CD25+ regulatory T cells (T reg), CD4+ T cells anergy, Th2 antitumor immunity diversion and myeloid suppressor cells); (c) tumor and host dependent (lack of co-stimulation molecules, immunosuppressive cytokines (vascular endothelial growth factor (VEGF), interleukin (IL)-10, prostaglandin (PG)E2, transforming growth factor (TGF)-,)). Cytokines and growth factors are involved in virtually all three types of mechanisms. These mechanisms are integrated with the current knowledge of tumor growth and inhibited apoptosis primarily mediated by cytokines and growth factors to propose an interpretation of the relationships among tumor cells, tumor stroma, and tumor-infiltrating lymphocytes. Tumor growth, defective immunorecognition and immunosuppression are the three principal effects considered responsible for immune evasion. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 3, 436-471, 2009 [source] Analysis of Streptococcus mutans biofilm proteins recognized by salivary immunoglobulin AMOLECULAR ORAL MICROBIOLOGY, Issue 5 2009T. Sanui Introduction:, The purpose of this study was to examine the Streptococcus mutans biofilm cellular proteins recognized by immunoglobulin A (IgA) in saliva from various caries-defined populations. Methods:, Biofilm and planktonic S. mutans UA159 cells were prepared. The proteins were extracted, separated by two-dimensional gel electrophoresis, transferred to blotting membranes, and probed for IgA using individual saliva samples from three groups of subjects; those who developed 0 caries (no active caries), 5,9 caries (medium), or more than 10 caries (severe) over a 12-month interval. Results:, Several proteins were recognized by salivary IgA in all groups of saliva but spot distribution and intensity varied greatly between the groups, and some proteins were recognized more strongly in biofilm cells than in planktonic culture, and vice versa. Furthermore, 15 proteins were only recognized by saliva from the ,no active caries' group, and four proteins were recognized by saliva samples from subjects in all three groups. Specifically, antigen I/II was recognized less in biofilm cells by caries-free saliva compared with planktonic cells. However, salivary IgA antibody to antigen I/II was absent in blots using saliva from the ,medium caries' and ,severe caries' groups. Conclusion:, The bacterial molecules recognized by caries-free saliva are significant factors for S. mutans caries formation, and their inhibition could be a therapeutic target. In addition, saliva of caries-free subjects includes significant IgA antibody against antigen I/II of S. mutans, indicating a protective mechanism. However, microorganisms may protect themselves from host immune attack by forming biofilms and decreasing expression of antigen I/II. [source] Can antiglycolipid antibodies present in HIV-infected individuals induce immune demyelination?NEUROPATHOLOGY, Issue 4 2000Steven Petratos Of the eight clinically defined neuropathies associated with HIV infection, there is compelling evidence that acute and chronic inflammatory demyelinating polyneuropathy (IDPN) have an autoimmune pathogenesis. Many non-HIV infected individuals who suffer from sensorymotor nerve dysfunction have autoimmune indicators. The immunopathogenesis of demyelination must involve neuritogenic components in myelin. The various antigens suspected to play a role in HIV-seronegative IDPN include (i) P2 protein; (ii) sulfatide (GalS); (iii) various gangliosides (especially GM1); (iv) galactocerebroside (GalC); and (v) glycoproteins or glycolipids with the carbohydrate epitope glucuronyl-3-sulfate. These glycoproteins or glycolipids may be individually targeted, or an immune attack may be raised against a combination of any of these epitopes. The glycolipids, however, especially GalS, have recently evoked much interest as mediators of immune events underlying both non-HIV and HIV-associated demyelinating neuropathies. The present review outlines the recent research findings of antiglycolipid antibodies present in HIV-infected patients with and without peripheral nerve dysfunction, in an attempt to arrive at some consensus as to whether these antibodies may play a role in the immunopathogenesis of HIV-associated inflammatory demyelinating polyneuropathy. [source] Neocortical neurones may be targeted by immune attack in anti-Yo paraneoplastic syndromeNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2008F. Aboul-Enein First page of article [source] Identification of a 55 kDa Haemonchus contortus excretory/secretory glycoprotein as a neutrophil inhibitory factorPARASITE IMMUNOLOGY, Issue 1 2008K. A. ANBU SUMMARY Haemonchus contortus is an economically important gastric parasite infecting sheep and goats. The parasite survives the host immune attack by releasing protective molecules. In the present study, a 55 kDa secretory glycoprotein (gp55) was identified that inhibited host neutrophils as judged by reduced H2O2 production by these cells. The binding of gp55 to neutrophils was confirmed by flow cytometry. This binding was mediated by cellular CD11b/CD18 integrin. The glycoprotein gp55 also bound to goat monocytes and lymphocytes and inhibited monocyte function. Using light fluorescence microscopy, gp55 was localized at the surface of adult worms. The absence of gp55 in the infective L3 larvae and its expression in the blood-feeding stage support a role for gp55 in the parasitic stage of the organism. [source] Mammalian Expression Cloning of Two Human Trophoblast Suppressors of Major Histocompatibility Complex GenesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2001J. A. PEYMAN PROBLEM: Human trophoblasts suppress interferon-, (IFN-,)-simulated expression of major histocompatibility complex (MHC) class II genes and thereby protect the conceptus from maternal immune attack. The mechanism of this suppression is poorly understood. METHOD OF STUDY: IFN-,-responsive HeLa cells were stably transfected with trophoblast cDNA expression libraries and screened by negative immunoselection with an antibody to HLA-DR. RESULTS: Two suppressor cDNAs were isolated. One encoded the untranslated RNA trophoblast STAT utron (TSU), which blocked STAT1 nuclear translocation and can theoretically form triplex RNA,DNA at the class II transactivator gene promoters. The other encoded the N-terminal 28 residues of chorionic somatomammotropin (hCS). TSU-related genes were detected in human and macaque, but not in mouse, genomic DNA. CONCLUSIONS: The genetics of two human trophoblast MHC suppressors suggest that these functions have been gained in human placenta in recent evolutionary history. TSU and hCS play critical roles in suppression of MHC genes, which may lead to silencing by DNA methylation. [source] Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis,ANNALS OF NEUROLOGY, Issue 3 2009Johannes Vogt MD Objective Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Methods We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high-precision stereology. Results Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor,related apoptosis-inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL-deficient T lymphocytes. Interpretation Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology. Ann Neurol 2009;66:310,332 [source] Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesisCANCER SCIENCE, Issue 8 2006Hui-Ching Wang Although hepatitis B virus (HBV) has been documented to cause hepatocellular carcinoma (HCC), the exact role of HBV in the development of HCC remains enigmatic. Several hypotheses have been proposed to explain the potential mechanism, including insertional mutagenesis of HBV genomes and transcriptional activators of HBV gene products such as hepatitis B x protein (HBx) and truncated middle S mutants. In the past few years, we have identified two types of large HBV surface antigens (LHBs) with deletions at the pre-S1 (,S1-LHBs) and pre-S2 (,S2-LHBs) regions in ground glass hepatocytes. The pre-S mutant LHBs are retained in the endoplasmic reticulum (ER) and escape from immune attack. The pre-S mutants, particularly ,S2-LHBs, are increasingly prevalent in patients with hepatitis B e antigen (HBeAg)-positive chronic HBV infection, ranging from 6% before the 3rd decade to 35% in the 6th decade. In HCC patients, the two pre-S mutants were detected in 60% of HCC patients, in the serum and in HCC tissues. Pre-S mutant LHBs can initiate ER stress to induce oxidative DNA damage and genomic instability. Furthermore, pre-S mutant LHBs can upregulate cyclooxygenase-2 and cyclin A to induce cell cycle progression and proliferation of hepatocytes. In transgenic mice, the pre-S mutants can induce dysplasia of hepatocytes and development of HCC. In a nested control study, the presence of pre-S mutants carried a high risk of developing HCC in HBV carriers. In summary, the findings we describe in this review suggest a potential role for HBV pre-S mutants in HBV-related hepatocarcinogenesis, providing a model of viral carcinogenesis associated with ER stress. (Cancer Sci 2006; 97: 683,688) [source] The critical role of type-1 innate and acquired immunity in tumor immunotherapyCANCER SCIENCE, Issue 9 2004Hiroaki Ikeda The discovery of a large array of tumor antigens has demonstrated that host lymphocytes can indeed recognize and destroy tumor cells as originally proposed in the cancer immunosurveillance hypothesis. Recent reports that led to the cancer immuno-editing concept also strongly support the immunosurveillance hypothesis, and they further indicate that the host immune system plays a critical role not only in promoting host protection against cancer but also in selecting tumors that can better escape from immune attack. Thus, it is now clear that T cells have the ability to recognize and destroy spontaneously arising tumors. However, the generation of antitumor immunity is often difficult in the tumor-bearing host because of various negative regulatory mechanisms. Here, we review our recent work on tumor immunotherapy, which utilizes the activation of type-1 innate and/or acquired immunity as a potent strategy to overcome immunosuppression in the tumor-bearing host. We have established a variety of tumor therapeutic protocols that aim to activate type-1 immunity, such as tumor-vaccine therapy with CpG encapsulated in liposomes, cell therapy using tumor-specific Th1 cells, and gene therapy using gene-engineered Th1 cells. We found that CpG encapsulated in liposomes stimulated IL-12-producing DC and induced IFN-,-producing NK cells, NKT cells, and tumor-specific CTL. Th1 cell therapy was also shown to be beneficial for acceleration of APC/Th1 cell-cell interaction in the DLN, which was critical for inducing tumor-specific CTL at the tumor site. Therefore, we conclude that the activation of type-1 innate and acquired immunity is crucial for tumor immunotherapy in order to overcome strong immunosuppression in the tumor-bearing host. 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