http://precedings.nature.com/subjects/immunology/ Recently posted documents in Immunology Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://precedings.nature.com/documents/3988/version/1 Cryptosporidium parvum is a zoonotic apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhoea in mammals worldwide. The organism is transmitted by ingestion of oocysts, which are shed in faeces, and completes its lifecycle in a single host.1 C. parvum is ubiquitous on dairy operations worldwide and is one of the leading causes of diarrhoea in calves on these farms.2,3 Here, for the first time, we describe the antibody response in a large group of cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine and the antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. Results of recent genotype surveys indicate that calves are the only major reservoir for C. parvum infections in humans.4 Human C. parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDs patients.4 Drug therapy against cryptosporidiosis is limited and not wholly efficacious in either humans or calves5, making development of an effective vaccine of paramount importance. To date, there is no commercially available effective vaccine against C. parvum, although passive immunization utilizing different zoite surface (glyco)proteins has showed promise.6-9 All cows we vaccinated produced an antibody response to the rCP15/60 vaccine and the magnitude of response correlated strongly with the subsequent level of antibody in their colostrum. All calves fed rCP15/60-immune colostrum showed a dose-dependent absorption of antibody. Our results demonstrate that vaccination of cows with rCP15/60 successfully induces antibodies against CP15/60 in their serum and colostrum and that these antibodies are then well absorbed when fed to neonatal calves. With further research, this C. parvum vaccine may well be a practical method of conferring passive protection to calves against cryptosporidiosis. Furthermore, a specifically targeted immune-colostrum may be valuable in protection and treatment of immunocompromised human patients with cryptosporidiosis. http://precedings.nature.com/documents/3988/version/1 Fri, 20 Nov 2009 12:18:51 UTC Antibody responses to a Cryptosporidium parvum rCP15/60 vaccine hdl:10101/npre.2009.3988.1 2009-11-20 Alexandra J. Burton Nature Precedings 2009-11-20T12:18:51Z Manuscript Immunology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3888/version/1 The cellular theory on the nature of life has been one of the first major advancements in biology. Viruses, however, are the most abundant life forms, and their exclusion from mainstream biology and the Tree of Life (TOL) is a major paradox in biology. This article presents a broad, unifying scenario on the origin and evolution of cellular and viral domains that challenges the conventional views about the history of life and supports a TOL that includes viruses. Co-evolution of viruses and their host cells has led to some of the most remarkable developments and transitions in the evolution of life, including the origin of non-coding DNA as a genomic protective device against viral insertion damage. However, one of the major fundamental evolutionary developments driven by viruses was probably the origin of cellular domains – Bacteria, Archaea and Eukarya – from the Last Universal Common Ancestor (LUCA) lineage, by evolving anti-fusion mechanisms. Consistent with a novel fusion/fission model for the population mode of evolution of LUCA, this paper presents a “cell-like world” model for the origin of life. According to this model the evolution of coupled replication, transcription and translation system (RT&T) occurred within non-living cell-like compartments (CCs). In this model, the ancestral ribosome originated as template-based RNA synthesizing machinery. The origin of the cellular genome as a centralized unit for storage and replication of genetic information within the CCs facilitated the evolution of the ancestral ribosome into a powerful translation machinery – the modern ribosome. After several hundred millions of years of providing an enclosed environment and fusion/fission based exchanges necessary for the population mode of evolution of the basic metabolism and the RT&T, the CCs evolved into the first living entities on earth – the LUCA lineage. The paper concludes with a proposal for a TOL that integrates the co-evolution of cellular and viral domains. This is one of a series of three articles that present a unifying scenario on the origin and evolution of viral and cellular domains, including the origin of life, which has significant t bio-medical implications and could lead to a significant paradigm shift in biology. http://precedings.nature.com/documents/3888/version/1 Fri, 23 Oct 2009 11:11:22 UTC A Unifying Scenario on the Origin and Evolution of Cellular and Viral Domains hdl:10101/npre.2009.3888.1 2009-10-23 Claudiu I. Bandea Nature Precedings 2009-10-23T11:11:22Z Manuscript Genetics & Genomics Immunology Microbiology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3820/version/1 Two important challenges to the use of serological assays for influenza surveillance include the substantial amount of experimental effort involved, and the inherent noisiness of serological data. Here, informed by the observation that log-transformed serological data (obtained from the hemagglutination-inhibition assay) exist in an effectively one-dimensional space, computational methods are developed for accurately and efficiently recovering unmeasured serological data from a sample of measured data, and systematically minimizing noise found in the measured data. Careful application of these methods would enable the collection of better-quality serological data on a greater number of circulating influenza viruses than is currently possible, and improve the ability to identify potential epidemic/pandemic viruses before they become widespread. Although the focus here is on influenza surveillance, the described methods are more widely applicable. http://precedings.nature.com/documents/3820/version/1 Mon, 05 Oct 2009 14:18:48 UTC New methods for analyzing serological data with applications to influenza surveillance hdl:10101/npre.2009.3820.1 2009-10-05 Wilfred Ndifon Nature Precedings 2009-10-05T14:18:48Z Manuscript Immunology Evolutionary Biology http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3824.1 T cells acquire various proteins from their cellular partners by the process of trogocytosis. We recently demonstrated that the FcγRIIIA receptor and its associated FcRγ are captured by T cells during their co-culture with FcγR-expressing target cells upon both antigen- or antibody-mediated stimulation. Interestingly, we found that FcR captured by T cells could bind ligands but did not transmit detectable intracellular signals or signaling-depending functions upon ligand binding suggesting their improper integration in the recipient T cell membrane. In this study, we provide morphological data in support of this hypothesis. Indeed, we show that the FcRγ-subunit, which we used as a fusion to GFP, was clearly present at the plasma membrane of donor cells, but was detected within structures that were in close contact of, but apparently not integrated in, the plasma membrane of recipient T cells. http://dx.doi.org/10.1038/npre.2009.3824.1 Mon, 05 Oct 2009 09:13:16 UTC Electron microscopy analysis of FcRγ localization after its capture by T cells by trogocytosis doi:10.1038/npre.2009.3824.1 2009-10-05 Denis Hudrisier Nature Precedings 2009-10-05T09:13:16Z Manuscript Immunology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3812/version/1 The detection and quantitation of exogenously administered biological macromolecules (e.g. vaccines, peptide and protein therapeutics) and their metabolites is frequently complicated by the presence of a complex endogenous mixture of closely related compounds. We describe a method that incorporates stable isotope labeling of the compound of interest allowing the selective screening of the intact molecule and all metabolites using a modified precursor ion scan. This method involves monitoring the low molecular weight fragment ions produced during MS/MS that distinguish isotopically labelled material from related endogenous compounds. All isotopically labelled substances can be selected using this scanning technique for further analysis whilst other unlabelled and irrelevant substances are ignored. The potential for this technique to be used in metabolism and pharmacokinetic experiments is discussed with specific examples looking at the metabolism of α-synuclein in serum and the brain. http://precedings.nature.com/documents/3812/version/1 Tue, 29 Sep 2009 09:11:02 UTC A novel strategy for the targeted analysis of protein and peptide metabolites hdl:10101/npre.2009.3812.1 2009-09-29 Anthony W. Purcell Nature Precedings 2009-09-29T09:11:02Z Manuscript Biotechnology Immunology Pharmacology http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3549.1 Multivalent ligands of CD22 for active targeting of B cells. Mary O’Reilly, Wei Hsu Chen, Gladys Completo, Ying Zeng, Satoshi Futakawa and Cory Rillahan and James C. Paulson, Departments of Chemical Physiology and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037The siglecs comprise 13 members of the immunoglobulin superfamily that recognize sialic acid containing glycans, and are differentially expressed on leukocytes and glial cells. The natural ligands of siglecs typically occur on the same cell (in cis) and/or on adjacent cells (in trans). Cis ligands mask the binding of multivalent synthetic sialoside ligands and are thought to regulate the activity of siglecs as modulators of cell signaling. However, synthetic ligands of sufficient avidity can compete with cis ligands, demonstrating a dynamic equilibrium of cis and trans ligand probes. We have explored the relationship between valency, affinity and geometry for achieving avidity sufficient to compete with cis ligands of CD22 (Siglec-2) in situ. A notable achievement is a hetero-bifunctional ligand approach to create multivalent ligands using antibodies as a protein scaffold. The ligand is comprised of a CD22 ligand, 9-biphenylcarboxyl-NeuAcα2-6Galβ1-4GlcNAc (BPCNeuAc), coupled to an antigen, 4-hydroxy-3-nitrophenylacetic acid (NP) (BPCNeuAc-NP). The BPCNeuAc-NP ligand is able to efficiently assemble complexes of anti-NP antibodies with CD22 on both asialo- and native B cells. Surprisingly, assembly of the tertiary complex occurs with anti-NP IgM (n=10), IgA (n=4) and IgG (n=2). The results suggest that spacing of ligands using an antibody optimizes the contribution of geometry to achieve high avidity with low valency. Other multivalent configurations also show promise for targeting B cells. In particular, liposomes bearing BPCNeuAc ligands bind avidly to B cells and are endocytosed. Thus, BPCNeuAc-lipososomes may prove effective in delivery of therapeutic agents to B cells (Supported by NIH grants GM60938, AI50143 ). http://dx.doi.org/10.1038/npre.2009.3549.1 Wed, 05 Aug 2009 08:41:59 UTC Multivalent ligands of CD22 for targeting of B cells doi:10.1038/npre.2009.3549.1 2009-08-05 James C. Paulson Nature Precedings 2009-08-05T08:41:59Z Presentation Biotechnology Cancer Chemistry Immunology Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3425/version/1 Chickens suffering from avian flu caused by H5N1 influenza virus are destined to die within 2 days due to a systemic inflammatory response. Since HVJ infection (1,2) and influenza virus infection (3,4) cause infected cells to activate homologous serum complement, the systemic inflammatory response elicited could be attributed to the unlimited generation of C5a anaphylatoxin of the complement system, which is a causative peptide of serious inflammation. In monkeys inoculated with a lethal dose of LPS (4 mg/kg body weight), inhibition of C5a by an inhibitory peptide termed AcPepA (5) rescued these animals from serious septic shock which would have resulted in death within a day (6). Therefore, we tested whether AcPepA could also have a beneficial effect on chickens with bird flu. On another front, enhanced production of endothelin-1 (ET-1) and the activation of mast cells (MCs) have been implicated in granulocyte sequestration (7). An endothelin receptor derived antisense homology box peptide (8) designated ETR-P1/fl was shown to antagonize endothelin A receptor (ET-A receptor) (9) and reduce such inflammatory responses as endotoxin-shock (10) and hemorrhagic shock (11), thereby suppressing histamine release in the circulation (12). Thus, we also administered ETR-P1/fl to bird flu chickens expecting suppression of a systemic inflammatory response. http://precedings.nature.com/documents/3425/version/1 Fri, 17 Jul 2009 14:45:18 UTC Rescue with an anti-inflammatory peptide of chickens infected H5N1 avian flu hdl:10101/npre.2009.3425.1 2009-07-17 Hidechika H. Okada Nature Precedings 2009-07-17T14:45:18Z Manuscript Immunology Microbiology Pharmacology http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2009.3405.1 Attempts to develop therapeutic vaccines against cervical cancer have been proven difficult. One of the major causes of the failure is due to the use of the wrong mouse models based on transplantable tumours in testing the efficacy of vaccines. Now that a transgenic epithelial mouse model has been developed to closely mimic cervical cancer, the mechanisms needed to eliminate this type of cancer could be studied. The E7 oncoprotein of Human Papillomavirus (HPV) is the most expressed HPV protein in cervical cancers and its continuous production is essential to maintain the cancerous state and therefore the obvious target in the development of vaccines. Skin grafts expressing the HPV 16 E7 protein (E7 autografts) are not spontaneously rejected from an MHC matched immunocompetent host. Interestingly, simultaneous placement of an MHC mismatched skin (allograft) next to an E7 autograft results in the E7 autograft rejection. However when the allograft also expresses E7, the E7 autograft is rejected more slowly. Autograft rejection requires CD8+ T cells, and is accelerated by removal of CD4+ T cells after placement of the E7 expressing allograft, suggesting induction of an E7 specific CD4+ regulatory T cell population by the E7 expressing allograft. This observation may have implications in designing effective vaccines and immunotherapy against cervical cancers in women. http://dx.doi.org/10.1038/npre.2009.3405.1 Wed, 08 Jul 2009 15:57:26 UTC Cervical Cancer-Associated Human Papillomavirus 16 E7 Oncoprotein Inhibits Induction of Anti-Cancer Immunity by a CD4+ T Cell Dependent Mechanism doi:10.1038/npre.2009.3405.1 2009-07-08 Marion E. G. Brunck Nature Precedings 2009-07-08T15:57:26Z Manuscript Cancer Immunology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3378/version/1 Background: Uncontrolled proliferation of T-cells is considered a barrier to the induction of transplantation tolerance by T regulatory cells. Therefore, cyclin kinase inhibitor p21, one of the most potent inhibitors of cell proliferation, may exert an important role in the induction/generation of T regulatory cells.Methods: CD4+CD25+ and CD4+CD25- cells were isolated from normal healthy blood donors (n=6), p21-/- mice (n=9) and wild type mice (n=9). Proliferation with and without cyclosporine was quantified by 3H-thymidine uptake assay (expressed as counts per minute) and FoxP3 mRNA was studied by real-time quantitative RT-PCR. Results: The difference in proliferation (p+CD25- T cells, CD4+25+ T cells from p21-/- mice lacked FoxP3 gene expression. T lymphocytes from wild type inhibited the proliferation of T lymphocytes from p21-/- mice similar to the effect of CD4+CD25+ T cells on the proliferation of CD4+CD25- cells. Conclusions: Presence of the p21 creates a milieu favorable for immune tolerance and consistent with antiproliferative and immunosuppressive effect of CD4+CD25+ T-regulatory cells. These findings support the notion that p21 could be used clinically in controlling allo-immune activation to achieve prolongation of graft survival. http://precedings.nature.com/documents/3378/version/1 Mon, 29 Jun 2009 12:17:13 UTC Cyclin kinase inhibitor p21: a mediator of immune tolerance: direct and indirect evidence hdl:10101/npre.2009.3378.1 2009-06-29 Ashwani Khanna Nature Precedings 2009-06-29T12:17:13Z Manuscript Immunology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/3361/version/1 Background and Aim of the work – We conducted a survey of varicella cases’ notifications in the immigrant population in the province of Ferrara, Italy.Materials and Methods – We collected notifications of infectious disease between 2002 and 2006. Results and discussion – At the end of 2006, the 4.5% (14252 subjects) of total population of the province of Ferrara and its province was represented of immigrants from foreign countries. In this context, between 2002 and 2006, a total of 1969 cases of varicella, including 3.1% related to migrants, were reported. Among immigrants, there were 36 cases in males, and 26 in females. The cases were notified in the 64.5% by the hospital emergency service, in the 16.1% by the paediatrician and in 19.4% by the general practitioner. The incidence appears similar in both populations in childhood: this fact could means an integration in the local epidemiology for varicella of the immigrant school-children. http://precedings.nature.com/documents/3361/version/1 Mon, 22 Jun 2009 20:27:23 UTC Varicella notification in immigrants: a brief report from Ferrara, Italy hdl:10101/npre.2009.3361.1 2009-06-22 Alessandro Cucchi Nature Precedings 2009-06-22T20:27:23Z Manuscript Immunology Microbiology http://creativecommons.org/licenses/by/3.0/