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https://www.readbyqxmd.com/read/28087528/engineering-mycobacteria-for-the-production-of-self-assembling-biopolyesters-displaying-mycobacterial-antigens-for-use-as-tuberculosis-vaccine
#1
Jason W Lee, Natalie A Parlane, Bernd H A Rehm, Bryce M Buddle, Axel Heiser
: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads produced in both E. coli and Lactococcus lactis displaying mycobacterial antigens were found to induce significant cell mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities which we hypothesized to have the potential to induce immunity...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28081217/collective-genetic-interaction-effects-and-the-role-of-antigen-presenting-cells-in-autoimmune-diseases
#2
Hyung Jun Woo, Chenggang Yu, Jaques Reifman
Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy body's own tissues. Both insufficient negative selection of self-reactive T cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key determinant of CD4+ T cell activation. Recent studies suggested that variants in the MHC region also exhibit significant non-additive interaction effects...
2017: PloS One
https://www.readbyqxmd.com/read/28075428/balanced-secretion-of-anti-cea-x-anti-cd3-diabody-chains-using-the-2a-self-cleaving-peptide-maximizes-diabody-assembly-and-tumor-specific-cytotoxicity
#3
K Mølgaard, M Compte, N Nuñez-Prado, S L Harwood, L Sanz, L Alvarez-Vallina
Adoptive transfer of genetically engineered human cells secreting bispecific T cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to its successful application. We have demonstrated that for gene-based bispecific antibody strategies, two-chain diabodies have a better safety profile than single-chain tandem scFvs, because their reduced tendency to form aggregates reduces the risk of inducing antigen-independent T cell activation...
January 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28066981/disruption-of-transplant-tolerance-by-an-incognito-form-of-cd8-t-cell-dependent-memory
#4
M K Nelsen, K S Beard, R J Plenter, R M Kedl, E T Clambey, R G Gill
Several approaches successfully achieve allograft tolerance in preclinical models but are challenging to translate into clinical practice. Many clinically relevant factors can attenuate allograft tolerance induction including intrinsic genetic resistance, peri-transplant infection, inflammation, and pre-existing anti-donor immunity. The prevailing view for immune memory as a tolerance barrier is that the host harbors memory cells that spontaneously cross-react to donor MHC antigens. Such pre-existing 'heterologous' memory cells have direct reactivity to donor cells and resist most tolerance regimens...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28059624/pre-clinical-development-of-gene-modification-of-hematopoietic-stem-cells-with-chimeric-antigen-receptors-for-cancer-immunotherapy
#5
Sarah M Larson, Laurel C Truscott, Tzu-Ting Chiou, Amie Patel, Roy Kao, Andy Tu, Tulika Tyagi, Xiang Lu, David Elashoff, Satiro N De Oliveira
Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of hematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary...
January 6, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28057434/atopic-dermatitis-immune-deviation-barrier-dysfunction-ige-autoreactivity-and-new-therapies
#6
REVIEW
Masutaka Furue, Takahito Chiba, Gaku Tsuji, Dugarmaa Ulzii, Makiko Kido-Nakahara, Takeshi Nakahara, Takafumi Kadono
Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD...
January 2, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28057182/auto-immunit%C3%A3-et-gestion-des-toxicit%C3%A3-s-des-traitements-par-anti-check-point-inhibiteurs
#7
Marie Senant, Delphine Giusti, Laurence Weiss, Marie-Agnès Dragon-Durey
AUTOIMMUNITY AND MANAGEMENT OF THE IMMUNE-RELATED ADVERSE EFFECTS OF THE IMMUNE CHECKPOINT INHIBITORS: The immune checkpoint molecules such as CTLA-4 and PD-1 are involved in the tolerance mechanisms preventing the immune system to react against the self-antigens. When these receptors expressed on the lymphocyte membrane, bind to their ligands, they induce a negative signal to the cell which becomes unable to be completely activated in the presence of its antigen. In a context of tumor, the infiltrating T cells are frequently exhausted due to the expression of CTLA-4 and PD-1 ligands by the microenvironment impairing the antitumoral immunity...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28049555/foxp3-positive-regulatory-t-cells-and-kidney-allograft%C3%A2-tolerance
#8
REVIEW
Alessandro Alessandrini, Laurence A Turka
Normal immune homeostasis is achieved by several mechanisms, and prominent among them is immunoregulation. Although several types of regulatory lymphocyte populations have been described, CD4 T cells expressing the FOXP3 transcription factor (FOXP3-positive regulatory T cells [FOXP3(+) Tregs]) are the best understood. This population of cells is critical for maintaining self-tolerance throughout the life of the organism. FOXP3(+) Tregs can develop within the thymus, but also under select circumstances, naive peripheral T cells can be induced to express FOXP3 and become stable Tregs as well...
December 31, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28046042/can-the-immune-system-perform-a-t-test
#9
Bruno Filipe Faria, Patricia Mostardinha, Fernao Vistulo de Abreu
The self-nonself discrimination hypothesis remains a landmark concept in immunology. It proposes that tolerance breaks down in the presence of nonself antigens. In strike contrast, in statistics, occurrence of nonself elements in a sample (i.e., outliers) is not obligatory to violate the null hypothesis. Very often, what is crucial is the combination of (self) elements in a sample. The two views on how to detect a change seem challengingly different and it could seem difficult to conceive how immunological cellular interactions could trigger responses with a precision comparable to some statistical tests...
2017: PloS One
https://www.readbyqxmd.com/read/28044415/modulation-of-alloimmune-response-by-commensal-gut-microbiota-and-potential-new-avenues-to-influence-the-outcome-of-allogeneic-transplantation-by-modification-of-the-gut-culture
#10
REVIEW
S Kanangat
Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses...
January 3, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28042013/antibody-engineering-of-a-cytotoxic-monoclonal-antibody-84-against-human-embryonic-stem-cells-investigating-the-effects-of-multivalency-on-cytotoxicity
#11
Maximilian Klement, Jiyun Zheng, Chengcheng Liu, Heng-Liang Tan, Victor Vai Tak Wong, Andre Boon-Hwa Choo, Dong-Yup Lee, Dave Siak-Wei Ow
Antibody fragments have shown targeted specificity to their antigens, but only modest tissue retention times in vivo and in vitro. Multimerization has been used as a protein engineering tool to increase the number of binding units and thereby enhance the efficacy and retention time of antibody fragments. In this work, we explored the effects of valency using a series of self-assembling polypeptides based on the GCN4 leucine zipper multimerization domain fused to a single-chain variable fragment via an antibody upper hinge sequence...
December 29, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/28040323/environmental-factor-and-inflammation-driven-alteration-of-the-total-peripheral-t-cell-compartment-in-granulomatosis-with-polyangiitis
#12
Anja Kerstein, Silke Schüler, Otávio Cabral-Marques, Juliane Fazio, Robert Häsler, Antje Müller, Silke Pitann, Frank Moosig, Sebastian Klapa, Christian Haas, Dieter Kabelitz, Gabriela Riemekasten, Steffen Wolters, Peter Lamprecht
Autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. Autoantibody production and an imbalance of effector and regulatory T-cells are hallmarks of autoimmune dysregulation. While expansion of circulating effector memory T-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral T-cell compartment have remained poorly understood so far. In granulomatosis with polyangiitis (GPA), a prototypical autoimmune disorder of unknown aetiology, we performed for the first time a combined approach using phenotyping, transcriptome and functional analyses of T-cell populations to evaluate triggers of memory T-cell expansion...
December 28, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28038685/grafted-c-kit-ssea1-eye-wall-progenitor-cells-delay-retinal-degeneration-in-mice-by-regulating-neural-plasticity-and-forming-new-graft-to-host-synapses
#13
Xi Chen, Zehua Chen, Zhengya Li, Chen Zhao, Yuxiao Zeng, Ting Zou, Caiyun Fu, Xiaoli Liu, Haiwei Xu, Zheng Qin Yin
BACKGROUND: Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28035349/monoclonal-antibodies-targeting-non-small-cell-lung-cancer-stem-like-cells-by-multipotent-cancer-stem-cell-monoclonal-antibody-library
#14
Kaiyue Cao, Yunzhi Pan, Long Yu, Xiong Shu, Jing Yang, Linxin Sun, Lichao Sun, Zhihua Yang, Yuliang Ran
Cancer stem cells (CSCs) are a rare subset of cancer cells that play a significant role in cancer initiation, spreading, and recurrence. In this study, a subpopulation of lung cancer stem-like cells (LCSLCs) was identified from non-small cell lung carcinoma cell lines, SPCA-1 and A549, using serum-free suspension sphere-forming culture method. A monoclonal antibody library was constructed using immunized BLAB/c mice with the multipotent CSC cell line T3A-A3. Flow cytometry analysis showed that 33 mAbs targeted antigens can be enriched in sphere cells compared with the parental cells of SPCA-1 and A549 cell lines...
December 22, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28031336/autophagy-in-dendritic-cells-and-b-cells-is-critical-for-the-inflammatory-state-of-tlr7-mediated-autoimmunity
#15
Chi G Weindel, Lauren J Richey, Abhiruchi J Mehta, Mansi Shah, Brigitte T Huber
Individuals suffering from autoimmune disorders possess a hyperactive cellular phenotype where tolerance to self-antigens is lost. Autophagy has been implicated in both the induction and prevention of autoimmunity, and modulators of this cellular recycling process hold high potential for the treatment of autoimmune diseases. In this study, we determine the effects of a loss of autophagy in dendritic cells (DCs), as well as both B cells and DCs, in a TLR7-mediated model of autoimmunity, similar to systemic lupus erythematosus, where both cell types are critical for disease...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28027005/serological-survey-of-hepatitis-b-immunity-in-healthcare-workers-in-catalonia-spain
#16
A Domínguez, L Urbiztondo, J M Bayas, E Borrás, S Broner, M Campins, J Costa, M Esteve
Healthcare workers (HCW) are exposed to preventable infectious diseases, notably hepatitis B (HB). The aim of this study was to determine the immunity of HCW against hepatitis B. We made a seroprevalence study using a self-administered survey and obtained blood samples. Antibodies against the HB surface antigen (anti-HBs) and against the HB core antigen (anti-HBc) were studied. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The adjusted OR were calculated using logistic regression. Of the 644 HCW who participated (29...
December 27, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28018356/plasmacytoid-dendritic-cells-respond-directly-to-apoptotic-cells-by-secreting-immune-regulatory-il-10-or-ifn-%C3%AE
#17
Joanne Simpson, Katherine Miles, Marta Trüb, Roisin MacMahon, Mohini Gray
Plasmacytoid dendritic cells (pDCs) play a pivotal role in driving the autoimmune disease systemic lupus erythematosus, via the secretion of IFN-α in response to nuclear self-antigens complexed with autoantibodies. Apoptotic cells, generated at sites of inflammation or secondary lymphoid organs, are exposed to activated pDCs and also express the same nuclear antigens on their cell surface. Here, we show that in the absence of autoantibodies, activated pDCs directly respond to apoptotic cell-expressed chromatin complexes by secreting IL-10 and IL-6, which also induces T cells to secrete IL-10...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018349/allorecognition-by-t-lymphocytes-and-allograft-rejection
#18
REVIEW
Jose Marino, Joshua Paster, Gilles Benichou
Recognition of donor antigens by recipient T cells in secondary lymphoid organs initiates the adaptive inflammatory immune response leading to the rejection of allogeneic transplants. Allospecific T cells become activated through interaction of their T cell receptors with intact allogeneic major histocompatibility complex (MHC) molecules on donor cells (direct pathway) and/or donor peptides presented by self-MHC molecules on recipient antigen-presenting cells (APCs) (indirect pathway). In addition, recent studies show that alloreactive T cells can also be stimulated through recognition of allogeneic MHC molecules displayed on recipient APCs (MHC cross-dressing) after their transfer via cell-cell contact or through extracellular vesicles (semi-direct pathway)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018338/the-pd1-pd-l1-2-pathway-from-discovery-to-clinical-implementation
#19
REVIEW
Kankana Bardhan, Theodora Anagnostou, Vassiliki A Boussiotis
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28013554/the-emerging-roles-of-b-cells-as-partners-and-targets-in-periodontitis
#20
Moncef Zouali
Initial studies of periodontal disease suggested that T cell-mediated immunity against oral Gram-negative microorganisms is a key player in the pathogenesis of this inflammatory disease. Recent investigations, however, revealed that B cells are also engaged. Given their chief role in innate-like and adaptive immune responses, B cells could exert protective functions in periodontitis. However, the periodontal bacteria-specific antibody response is generally unable to halt disease progression in affected subjects, suggesting that the antibodies produced could exhibit low anti-bacterial blocking functions or opsonophagocytic potential, and/or unfavorable effects...
December 26, 2016: Autoimmunity
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