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1
Trezise, Stephanie, Alexander Karnowski, Pasquale Fedele, Sridurga Mithraprabhu, Yang Liao, Kathy D’Costa, Andrew Kueh, et al. "Mining the Plasma Cell Transcriptome for Novel Cell Surface Proteins." International Journal of Molecular Sciences 19, no. 8 (July 24, 2018): 2161. http://dx.doi.org/10.3390/ijms19082161.
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Antibody Secreting Cells (ASCs) are a fundamental component of humoral immunity, however, deregulated or excessive antibody production contributes to the pathology of autoimmune diseases, while transformation of ASCs results in the malignancy Multiple Myeloma (MM). Despite substantial recent improvements in treating these conditions, there is as yet no widely used ASC-specific therapeutic approach, highlighting a critical need to identify novel methods of targeting normal and malignant ASCs. Surface molecules specifically expressed by the target cell population represent ideal candidates for a monoclonal antibody-based therapy. By interrogating the ASC gene signature that we previously defined we identified three surface proteins, Plpp5, Clptm1l and Itm2c, which represent potential targets for novel MM treatments. Plpp5, Clptm1l and Itm2c are highly and selectively expressed by mouse and human ASCs as well as MM cells. To investigate the function of these proteins within the humoral immune system we have generated three novel mouse strains, each carrying a loss-of-function mutation in either Plpp5, Clptm1l or Itm2c. Through analysis of these novel strains, we have shown that Plpp5, Clptm1l and Itm2c are dispensable for the development, maturation and differentiation of B-lymphocytes, and for the production of antibodies by ASCs. As adult mice lacking either protein showed no apparent disease phenotypes, it is likely that targeting these molecules on ASCs will have minimal on-target adverse effects.
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Zhang, Yi, Jun Li, Ya-Min Zhang, Xiao-Ming Zhang, and Juan Tao. "Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases." Journal of Immunology Research 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/247426.
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Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) is one of the receptors of B cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL). TACI is a regulator in the immune responses. TACI inhibits B cell expansion and promotes the differentiation and survival of plasma cells. The mechanisms underlying these effects probably involve changed expressions of some crucial molecules, such as B lymphocyte induced maturation protein-1 (Blimp-1) and inducible T-cell costimulator ligand (ICOSL) in B cells and/or plasma cells. However, abnormal TACI signaling may relate to autoimmune disorders. Common variable immune deficiency (CVID) patients with heterozygous mutations inTACIalleles increase susceptibility to autoimmune diseases.Taci−/−mice and BAFF transgenic mice both develop signs of human SLE. These findings that indicate inappropriate levels of TACI signaling may disrupt immune system balance, thereby promoting the development of autoimmune diseases. In this review, we summarize the basic characteristics of the TACI ligands BAFF and APRIL, and detail the research findings on the role of TACI in humoral immunity. We also discuss the possible mechanisms underlying the susceptibility of CVID patients withTACImutations to autoimmune diseases and the role of TACI in the pathogenesis of SLE.
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Nieman, David, Arnoud Groen, Artyom Pugachev, Andrew Simonson, Kristine Polley, Karma James, Bassem El-Khodor, Saradhadevi Varadharaj, and Claudia Hernández-Armenta. "Blood Proteomics-Based Detection of Upregulated Lipid Metabolism and Immune Dysfunction in an Elite Adventure Athlete Trekking Across Antarctica." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1760. http://dx.doi.org/10.1093/cdn/nzaa066_015.
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Abstract Objectives Proteomics when combined with psychological, nutrition, and performance measures may serve as a useful monitoring system for immune dysfunction, training distress, and exercise-induced muscle damage and exhaustion in athletes. Global proteomics monitoring of an elite adventure athlete (age 33 years) was conducted over a 28-week period that culminated in the successful, unassisted 2-month trek across Antarctica (1500 km). Methods Training distress was monitored weekly using the 19-item, validated Training Distress Scale (TDS). Weekly dried blood spot (DBS) specimens were collected via fingerprick blood drops onto standard blood spot cards. DBS proteins were measured with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) in data-independent acquisition (DIA) mode, and 712 proteins were identified and quantified. Results The participant experienced a decrease of 11.4 kg in body mass during the Antarctica trek. The 28-week period was divided into time segments based on TDS scores, and a contrast analysis between weeks 5–8 (low TDS) and weeks 20–23 (high TDS, last month of Antarctica trek) showed that 31 proteins (n = 20 immune related, n = 14 nutrition related with n = 8 in dual roles) were upregulated and 35 (n = 17 immune related) were downregulated. Protein-protein interaction (PPI) networks and gene ontology (GO) biological process analysis supported an increase in plasma lipoprotein particle remodeling, regulation of lipid transport, retinoid metabolic process, and vitamin transport due to high energy intake (7048 kcal/d). PPI networks also supported a dichotomous immune response. GO terms for the upregulated immune proteins showed an increase in regulation of the immune system process, especially inflammation, complement activation, and leukocyte mediated immunity. GO terms for the downregulated immune-related proteins indicated a decrease in several aspects of the overall immune system process including neutrophil degranulation and the antimicrobial humoral response. Conclusions These proteomics data support a dysfunctional immune response in an elite adventure athlete during a sustained period of mental and physical distress, high energy intake, and significant loss of body mass while trekking solo across Antarctica. Funding Sources Standard Process, Inc., Palmyra, WI.
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Tao, Yu, Gaojian Li, Wenqian Zheng, Jianhong Shu, Jian Chen, Fang Yang, Yuehong Wu, and Yulong He. "Development of a Combined Genetic Engineering Vaccine for Porcine Circovirus Type 2 and Mycoplasma Hyopneumoniae by a Baculovirus Expression System." International Journal of Molecular Sciences 20, no. 18 (September 9, 2019): 4425. http://dx.doi.org/10.3390/ijms20184425.
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Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are the main pathogens for mycoplasmal pneumonia of swine (MPS) and post-weaning multisystemic wasting syndrome (PMWS), respectively. Infection by these pathogens often happens together and causes great economic losses. In this study, a kind of recombinant baculovirus that can display P97R1P46P42 chimeric protein of Mhp and the capsid (Cap) protein of PCV2 was developed, and the protein location was identified. Another recombinant baculovirus was constructed without tag proteins (EGFP, mCherry) and was used to evaluate the immune effect in experiments with BALB/c mice and domestic piglets. Antigen proteins P97R1P46P42 and Cap were expressed successfully; both were anchored on the plasma membrane of cells and the viral envelope. It should be emphasized that in piglet immunization, the recombinant baculovirus vaccine achieved similar immunological effects as the mixed commercial vaccine. Both the piglet and mouse experiments showed that the recombinant baculovirus was able to induce humoral and cellular responses effectively. The results of this study indicate that this recombinant baculovirus is a potential candidate for the further development of more effective combined genetic engineering vaccines against MPS and PMWS. This experiment also provides ideas for vaccine development for other concomitant diseases using the baculovirus expression system.
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Zhong, Xiaofen, Zufeng Guo, Huanghao Yang, Lisheng Peng, Yong Xie, Tin-Yau Wong, Sik-To Lai, and Zhihong Guo. "Amino terminus of the SARS coronavirus protein 3a elicits strong, potentially protective humoral responses in infected patients." Journal of General Virology 87, no. 2 (February 1, 2006): 369–73. http://dx.doi.org/10.1099/vir.0.81078-0.
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The 3a protein of severe acute respiratory syndrome (SARS)-associated coronavirus is expressed and transported to the plasma membrane in tissue cells of infected patients. Its short N-terminal ectodomain was found to elicit strong humoral responses in half of the patients who had recovered from SARS. The ectodomain-specific antibodies from the convalescent-phase plasma readily recognized and induced destruction of 3a-expressing cells in the presence of the human complement system, demonstrating their potential ability to provide immune protection by recognizing and eliminating SARS coronavirus-infected cells that express the target protein. In addition, when coupled to a carrier protein, the ectodomain peptide elicited 3a-specific antibodies in mice and rabbit at high titres. These results showed that the N terminus of the 3a protein is highly immunogenic and elicits potentially protective humoral responses in infected patients. Therefore, the short extracellular domain may be a valuable immunogen in the development of a vaccine for infectious SARS.
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Mahmoud, A. M. A., E. J. De Luna-Santillana, X. Guo, and Mario A. Rodríguez-Pérez. "Parasitism by Cotesia flavipes alters the haemocyte population and phenoloxidase activity of the sugarcane borer, Diatraea saccharalis." Canadian Entomologist 144, no. 4 (May 18, 2012): 599–608. http://dx.doi.org/10.4039/tce.2012.41.
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AbstractParasitism of Diatraea saccharalis (Fabricius) (Lepidoptera: Crambidae) larvae by Cotesia flavipes Cameron (Hymenoptera: Braconidae) or injection of C. flavipes polydnavirus causes numerous alterations in host physiology including developmental arrest, abrogation of host immunity, and biochemical changes in proteins, carbohydrates, glycogen, and lipids. This study focused on changes in haemocyte composition occurring in the cellular immune system of parasitised D. saccharalis larvae. We also analysed the effects of parasitisation by C. flavipes on humoral immunity in terms of phenoloxidase (PO) activity in the host. In nonparasitised D. saccharalis larvae, granular cells represented the main haemocyte type (39%) and plasmatocytes were also present at around 35% among the total haemocytes. The percentages of these two major haemocytes decreased significantly in parasitised larvae after 6 days of parasitoid oviposition and the total haemocyte counts exhibited a significant reduction in parasitised larvae 3 and 6 days following parasitisation. The parasitised larvae also showed a significant decrease in humoral immune capacity as evidenced by reduction of PO activity. Moreover, the plasma had more PO activity than the haemocytes and the parasitised larvae showed less PO activity than the control larvae. This research demonstrates that the parasitism of C. flavipes adversely affects the total haemocyte populations and PO activity of D. saccharalis larvae, which would contribute to host immunosuppression.
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Matsumoto, A. K., J. Kopicky-Burd, R. H. Carter, D. A. Tuveson, T. F. Tedder, and D. T. Fearon. "Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19." Journal of Experimental Medicine 173, no. 1 (January 1, 1991): 55–64. http://dx.doi.org/10.1084/jem.173.1.55.
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The complement system augments the humoral immune response, possibly by a mechanism that involves the B lymphocyte membrane receptor, CR2, which binds the C3dg fragment of C3 and triggers several B cell responses in vitro. The present study demonstrates that CR2 associates with a complex of membrane proteins that may mediate signal transduction by ligated CR2. Monoclonal antibodies to CR2 immunoprecipitated from digitonin lysates of Raji B lymphoblastoid cells a membrane complex containing CR2, approximately equimolar amounts of CD19, which is a member of the immunoglobulin superfamily, and three unidentified components: p130, p50, and p20. The complex, which was immunoprecipitated also with anti-CD19, could be dissociated by Nonidet P-40, accounting for its absence in previous studies of CR2. Expression of recombinant CR2 and CD19 in K562 erythroleukemia cells led to formation of a complex that contained not only these two proteins but also p130, p50, and p20, and another component, p14. These unidentified components of the CR2/CD19 complex coimmunoprecipitated with CD19 and not with CR2 from singly transfected cells, indicating primary association with the former. CD19 replicated the capacity of CR2 to interact synergistically with mIgM for increasing free intracellular Ca2+, suggesting that the complex mediates this function of CR2. Therefore, CR2 associates directly with CD19 to become a ligand-binding subunit of a pre-existing signal transduction complex of the B cell that may be representative of a family of membrane protein complexes. This interaction between the complement and immune systems differs from that between immunoglobulin and Clq by involving membrane rather than plasma proteins, and by having complement involved in the afferent phase of the immune response.
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Rafei, Moutih, Jeremy Hsieh, MengYang Li, and Jacques Galipeau. "Marrow-Derived Mesenchymal Stromal Cells Can Block an Antigen-Driven Humoral Response by Suppressing Plasma Cell Activity Via Production of CCL2." Blood 110, no. 11 (November 16, 2007): 1350. http://dx.doi.org/10.1182/blood.v110.11.1350.1350.
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Abstract Marrow-derived Mesenchymal Stromal Cells (MSCs) have been demonstrated to possess powerful immunomodulatory suppressive properties. In vitro studies by many groups have shown that MSCs can suppress th1 immune responses as exemplified by in vitro blockade of a 2-way mixed lymphocyte reaction (MLR) by an assortment of mechanisms including production of soluble factors such as: nitric oxide, transforming growth factor-β, IGF-1 and hepatocyte growth factor. Lately, interesting studies have also demonstrated the potency of MSCs in modulating humoral immunity by inhibiting B-cell migration, proliferation as well as immunoglobulin secretion in vitro. We here sought to further define the ability of autologous MSCs in modulating an ovalbumin (OVA) antigen-specific humoral response in normal immune competent C57BL/6 mice. Immunologically naïve mice were vaccinated with 50 ug of recombinant chicken ovalbumin protein followed by a boost dose 2 weeks later. All mice developed a robust IgM and IgG anti-OVA antibody response as measured in serial plasma samples over time. Following establishment of anti-OVA humoral immunity, test mice (n=10) were administered 1.5 million autologous MSCs in the peritoneal cavity twice at one month interval. Compared with same-treated controls (n=10), we found that MSC treated mice significantly suppressed anti-OVA IgG titer. This inhibitory effect requires metabolically active MSCs since live MSCs inhibited anti-OVA IgG secretion in ELISPOT assays, whereas paraformaldehyde fixed MSCs had no effect. Interestingly, the addition of MSC conditioned media directly on spleen-derived plasma cells derived form OVA immunized mice inhibited OVA-specific IgG secretion in vitro. A cytokine array screen on MSC secretome identified CCL2 as a possible effector molecule in suppressing plasma cell activity, and we found that anti-CCL2 neutralizing antibodies abolished the suppressive effect of MSCs on plasma cells. In conclusion, we have found that MSCs can suppress a pre-established humoral response to a defined antigen in vivo. This effect is contact independent, and requires metabolically active MSCs. MSC-derived CCL2 appears to be a key suppressor of antigen-specific immunoglobulin in this system.
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González-González, María, José María Sayagués, Luis Muñoz-Bellvís, Carlos Eduardo Pedreira, Marcello L. R. de Campos, Jacinto García, José Antonio Alcázar, et al. "Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays." Cancers 13, no. 11 (May 31, 2021): 2718. http://dx.doi.org/10.3390/cancers13112718.
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Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.
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Sikora, Marta, Ewa Bretes, Joanna Perła-Kaján, Izabela Lewandowska, Łukasz Marczak, and Hieronim Jakubowski. "Genetic Attenuation of Paraoxonase 1 Activity Induces Proatherogenic Changes in Plasma Proteomes of Mice and Humans." Antioxidants 9, no. 12 (November 28, 2020): 1198. http://dx.doi.org/10.3390/antiox9121198.
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High-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-inflammatory, antioxidative, and antithrombotic activities. Paraoxonase 1 (PON1), carried on HDL in the blood, can contribute to these antiatherogenic activities. The PON1-Q192R polymorphism involves a change from glutamine (Q variant) to arginine (R variant) at position 192 of the PON1 protein and affects its enzymatic activity. The molecular basis of PON1 association with cardiovascular and neurological diseases is not fully understood. To get insight into the function of PON1 in human disease, we examined how genetic attenuation of PON1 levels/activity affect plasma proteomes of mice and humans. Healthy participants (48.9 years old, 50% women) were randomly recruited from the Poznań population. Four-month-old Pon1−/− (n = 17) and Pon1+/+ (n = 8) mice (50% female) were used in these experiments. Plasma proteomes were analyzed using label-free mass spectrometry. Bioinformatics analysis was carried out using the Ingenuity Pathway Analysis (IPA) resources. PON1-Q192R polymorphism and Pon1−/− genotype induced similar changes in plasma proteomes of humans and mice, respectively. The top molecular network, identified by IPA, affected by these changes involved proteins participating in lipoprotein metabolism. Other PON1 genotype-dependent proteomic changes affect different biological networks in humans and mice: “cardiovascular, neurological disease, organismal injury/abnormalities” in PON1-192QQ humans and “humoral immune response, inflammatory response, protein synthesis” and “cell-to-cell signaling/interaction, hematological system development/function, immune cell trafficking” in Pon1−/− mice. Our findings suggest that PON1 interacts with molecular pathways involved in lipoprotein metabolism, acute/inflammatory response, and complement/blood coagulation that are essential for blood homeostasis. Modulation of those interactions by the PON1 genotype can account for its association with cardiovascular and neurological diseases.
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Fekete, S. Gy, and R. O. Kellems. "Interrelationship of feeding with immunity and parasitic infection: a review." Veterinární Medicína 52, No. 4 (January 7, 2008): 131–43. http://dx.doi.org/10.17221/2028-vetmed.
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Authors overlook the recent findings in the field of the complex interrelationship among nutrition, immune status and parasitic infestation. After summarizing the general characteristics of the active immune system, they describe the first period of the systemic immune response, the acute phase reaction. The cause of drastical decrease in serum zinc concentration is redistribution into the liver and lymphocyte metallothioneins. Immune deficiency correlates only indirectly with the nutrition. Ingestion of feed mycotoxins (e.g. T-2 toxin) and peroxides causes lymphocytes depletion in the lymphoid organs. Events of immunological stress are a special form of homeorrhetic control. Lack of energy and protein hardly damages the humoral immunity. Undernutrition fundamentally affects the cell-mediated immune response and the complement production. In animals, the lack of calcium, magnesium, iron, zinc, copper, iodine and selenium has been associated with signs of immunodeficiency. The concentrations of trace elements required for healthy animals are often below what is required for animals experiencing an immunological challenge. Zinc has both specific and aspecific role in the immune defence mechanism. Zinc regulates the maturation and function of immune cells, among others by protecting developing lymphocytes from apoptosis. As part of the zinc-finger proteins, may influence DNA transcription. The thymus synthesizes a 9-amino acid peptide hormone, the thymulin, which is activated after having bound zinc. Selenium has a vitamin E-independent immunostimulant effect in the marginally supplied animals. Active form of vitamin D<sub>3</sub> regulates transcription at cell level, acts as an immunomodulator and promotes phagocytosis. Lack of essential fatty acids in the diet of experimental animals caused atrophy of lymphoid organs and the reduction both the T-cell mediated and the independent immune response. Practical application of the new immunological findings is the segregated early weaning (SEW). Feed allergy results either in immediate hypersensitivity reaction within 1 to 2 hours or a T cell-mediated delayed hypersensitivity reaction within days. Under a certain number of worms (“threshold value”) the host organism did not show detectable changes. Parasitic infection changes the body and skeletal composition: the water content increases, that of protein and fat drop; the calcium and phosphorus concentration of bones decreases. Helminths, developing in the animal, may cause serious local lesions; anaemia and the change of plasma proteins. Worms’ toxins stimulate the production of gastrointestinal hormones, causing reduction in voluntary feed intake. Rabbits with biliary coccidiosis significantly decreased voluntary feed intake and the digestibility of the fats. The extent of infection and the oocyte excretion of <i>Eimeria maxima</i> in growing chickens showed a strong negative correlation with the plasma carotenoid level and strong positive correlation with the blood nitrogen oxide and γ-interferon concentration.
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Meeks, Shannon, Ernest T. Parker, Amy L. Dunn, John F. Healey, and Pete Lollar. "Proteolytically Inactivatable Factor VIII is Less Immunogenic than Factor VIII in a Murine Hemophilia A Model." Blood 114, no. 22 (November 20, 2009): 27. http://dx.doi.org/10.1182/blood.v114.22.27.27.
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Abstract Abstract 27 Patients with hemophilia A have a congenital deficiency of the factor VIII (fVIII) protein due to a mutation in the fVIII gene that frequently leads to absence of detectable expression of fVIII. Accordingly, the therapeutic replacement fVIII protein potentially is recognized as non-self by the immune system. Thirty percent of patients with severe hemophilia A develop detectable inhibitory anti-fVIII antibodies (inhibitors). Additionally, greater than 90 percent of hemophilia A mice treated with human fVIII develop inhibitors using dosing schedule that mimics use in humans. Because fVIII is an immunologically foreign protein, it might be expected that a hemophilia A patient would make a fVIII inhibitor. However, intravenous injection of soluble proteins in either humans or rodents usually results in tolerance rather than a humoral immune response. One major difference between fVIII and other proteins is that it is released from its large carrier protein von Willebrand factor (VWF) and is potentially exposed to the immune system at sites of active hemostasis and inflammation. Heat-inactivated, denatured fVIII, which maintains all T-cell epitopes but lacks several B-cell epitopes, is less immunogenic than native fVIII, suggesting that fVIII-dependent thrombin generation along the intrinsic pathway of blood coagulation may provide co-stimulatory signals necessary for the immune response (Skupsky BS, Zhang A, Scott DW Blood 2008; 112:1220a). We constructed a B domain-deleted human fVIII mutant, designated fVIIIi, which contains alanine substitutions at two critical thrombin cleavage sites, Arg372 and Arg1689, and purified it to homogeneity. FVIIIi does not develop procoagulant activity and is not released from VWF in response to thrombin. Therefore fVIIIi is less likely than wild-type fVIII to be exposed to the immune system at sites of active hemostasis and inflammation. Additionally, VWF binds to the immunodominant fVIII C2 domain and potentially hides part of fVIII from the immune system. FVIIIi was antigenically intact judging from intact binding to a panel of11 mouse anti-fVIII monoclonal antibodies whose epitope specificity was represented by all five domains of BDD fVIII. The immunogenicity of wild-type fVIII and fVIIIi was compared in a murine hemophilia A model in which groups of 25 mice received 8 weekly injections of physiologic doses of fVIII. Plasma was collected weekly for total anti-fVIII antibody titers by ELISA and one week following the last injection for total anti-fVIII antibody titers, inhibitor titers by Bethesda assay and for epitope mapping. Mice treated with fVIIIi had significantly lower levels of inhibitory as well as total anti-fVIII antibodies than mice treated with wild-type fVIII. Domain mapping using single human domain hybrid human/porcine molecules as ELISA antigens revealed that hemophilia A mice broadly recognized all fVIII domains in response to either wild-type or fVIIIi, although fVIIIi produced less anti-light chain antibodies. Mice in both the wild-type fVIII and fVIIIi groups produced antibodies that recognized the phospholipid-binding site of the C2 domain, even though this site overlaps the VWF binding site on fVIII. There was no difference in the isotype spectrum of the antibodies made to fVIII or fVIIIi. This study indicates that inactivatable fVIII is less immunogenic than native fVIII and suggests that the immunogenicity of fVIII is related either to its interaction with VWF or to events triggered by activation of the coagulation mechanism. Disclosures: No relevant conflicts of interest to declare.
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Huijbregts, Richard P. H., E. Scott Helton, Katherine G. Michel, Steffanie Sabbaj, Holly E. Richter, Paul A. Goepfert, and Zdenek Hel. "Hormonal Contraception and HIV-1 Infection: Medroxyprogesterone Acetate Suppresses Innate and Adaptive Immune Mechanisms." Endocrinology 154, no. 3 (March 1, 2013): 1282–95. http://dx.doi.org/10.1210/en.2012-1850.
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Abstract Recent observational studies indicate an association between the use of hormonal contraceptives and acquisition and transmission of HIV-1. The biological and immunological mechanisms underlying the observed association are unknown. Depot medroxyprogesterone acetate (DMPA) is a progestin-only injectable contraceptive that is commonly used in regions with high HIV-1 prevalence. Here we show that medroxyprogesterone acetate (MPA) suppresses the production of key regulators of cellular and humoral immunity involved in orchestrating the immune response to invading pathogens. MPA inhibited the production of interferon (IFN)-γ, IL-2, IL-4, IL-6, IL-12, TNFα, macrophage inflammatory protein-1α (MIP-1α), and other cytokines and chemokines by peripheral blood cells and activated T cells and reduced the production of IFNα and TNFα by plasmacytoid dendritic cells in response to Toll-like receptor-7, -8, and -9 ligands. Women using DMPA displayed lower levels of IFNα in plasma and genital secretions compared with controls with no hormonal contraception. In addition, MPA prevented the down-regulation of HIV-1 coreceptors CXCR4 and CCR5 on the surface of T cells after activation and increased HIV-1 replication in activated peripheral blood mononuclear cell cultures. The presented results suggest that MPA suppresses both innate and adaptive arms of the immune system resulting in a reduction of host resistance to invading pathogens.
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Toubi, Elias, and Zahava Vadasz. "Hemostasis in Allergy." Seminars in Thrombosis and Hemostasis 44, no. 07 (June 19, 2018): 669–75. http://dx.doi.org/10.1055/s-0038-1648232.
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AbstractThe involvement of the hemostatic system in immune-mediated inflammation is widely reported. Many coagulation factors play a role in the pathogenesis of autoimmune diseases, such as systemic vasculitis and systemic lupus erythematosus. Hemostatic disorders are also involved in asthma and chronic spontaneous urticaria (CSU). Factor XIIa (FXIIa) was one of the first coagulation factors implicated in inducing both humoral and cellular responses and is therefore considered a prime new therapeutic target in immune-mediated inflammation. The involvement of coagulation factors, such as tissue factor and fibrinogen, in the pathogenesis of asthma has been reported. The finding of platelet activation in asthma also indicates a link between bronchial inflammation and hemostasis. The pathogenesis of mast cell degranulation and CSU was also shown to be associated with the activation of hemostatic factors such as fibrinogen and FXIIa. Increased plasma levels of D-dimer have been widely reported as a biological marker for the duration and severity of CSU. In addition, endothelial-induced cell activation by the kallikrein–high molecular weight complex and the release of heat shock protein 90 was shown to be involved in mast cell degranulation disorders. In this narrative review, the authors aim to summarize the role of hemostasis in inflammation, asthma, and CSU by focusing on the increasing information linking hemostatic factors and immune-mediated disorders.
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Machado, Marina, Sofia Engrola, Rita Colen, Luis E. C. Conceição, Jorge Dias, and Benjamín Costas. "Dietary methionine supplementation improves the European seabass (Dicentrarchus labrax) immune status following long-term feeding on fishmeal-free diets." British Journal of Nutrition 124, no. 9 (June 1, 2020): 890–902. http://dx.doi.org/10.1017/s0007114520001877.
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AbstractMethionine is a limiting amino acid (AA) in fish diets, particularly in those containing high levels of plant protein (PP), and is key in the immune system. Accordingly, outcome on the fish immune mechanisms of methionine-deficient and methionine-supplemented diets within the context of 0 % fishmeal formulation, after a short and prolonged feeding period, was studied in European seabass (Dicentrarchus labrax). For this, seabass juveniles were fed a (i) fishmeal-free diet, meeting AA requirements, but deficient in methionine (MET0·65); (ii) as control, the MET0·65 supplemented with l-methionine at 0·22 % of feed weight (CTRL); (iii) two diets, identical to MET0·65 but supplemented at 0·63 and 0·88 % of feed weight of l-methionine (MET1·25 and MET1·5, respectively); and (iv) a fishmeal-based diet (FM), as positive control. After 2 and 12 weeks of feeding, blood and plasma were sampled for leucocyte counting and humoral parameter assays and head-kidney collected for gene expression. After 2 weeks of feeding, a fishmeal-free diet supplemented with methionine led to changes in the expression of methionine- and leucocyte-related genes. A methionine immune-enhancer role was more evident after 12 weeks with an increased neutrophil percentage and a decreased expression of apoptotic genes, possibly indicating an enhancement of fish immunity by methionine dietary supplementation. Furthermore, even though CTRL and FM present similar methionine content, CTRL presented a reduced expression of several immune-related genes indicating that in a practical PP-based diet scenario, the requirement level of methionine for an optimal immune status could be higher.
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Saadi, S., and J. L. Platt. "Transient perturbation of endothelial integrity induced by natural antibodies and complement." Journal of Experimental Medicine 181, no. 1 (January 1, 1995): 21–31. http://dx.doi.org/10.1084/jem.181.1.21.
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The barrier function of blood vessels is though to be regulated at least in part by endothelium. This concept is supported by the dramatic loss of barrier function occurring in the hyperacute rejection of vascularized grafts mediated by anti-endothelial cell (EC) antibodies and complement. In this process, the endothelium is not destroyed but instead loses the ability to retain blood cells and plasma proteins within capillaries. The noncytotoxic mechanism that allows this change in EC function has been unknown. Here we report that within 10 to 20 min of exposure to human xenoreactive natural antibodies and complement, porcine EC undergo alterations in cell shape and in the cytoskeleton that disrupt monolayer integrity and lead to formation of intercellular gaps. Gap formation is not associated with cell death but requires the complement complex C5b67. The gaps induced by anti-EC antibodies and complement are transient; gap closure requires formation of C5b-9 complexes on the cells and the rate of recovery depends on the release of cellular products into the medium. Preincubation of EC with dibutyryl cAMP (0.5 mM) prevents gap formation and disruption of the cytoskeleton caused by antibodies and complement. These results provide evidence that the integrity of endothelium is regulated by components of the complement system and suggest a mechanism that may explain the prominent loss of endothelial integrity seen in humoral immune responses.
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Frescas, David, Christelle M. Roux, Semra Aygun-Sunar, Anatoli S. Gleiberman, Peter Krasnov, Oleg V. Kurnasov, Evguenia Strom, et al. "Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody." Proceedings of the National Academy of Sciences 114, no. 9 (February 13, 2017): E1668—E1677. http://dx.doi.org/10.1073/pnas.1614661114.
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Studying the phenomenon of cellular senescence has been hindered by the lack of senescence-specific markers. As such, detection of proteins informally associated with senescence accompanies the use of senescence-associated β-galactosidase as a collection of semiselective markers to monitor the presence of senescent cells. To identify novel biomarkers of senescence, we immunized BALB/c mice with senescent mouse lung fibroblasts and screened for antibodies that recognized senescence-associated cell-surface antigens by FACS analysis and a newly developed cell-based ELISA. The majority of antibodies that we isolated, cloned, and sequenced belonged to the IgM isotype of the innate immune system. In-depth characterization of one of these monoclonal, polyreactive natural antibodies, the IgM clone 9H4, revealed its ability to recognize the intermediate filament vimentin. By using 9H4, we observed that senescent primary human fibroblasts express vimentin on their cell surface, and MS analysis revealed a posttranslational modification on cysteine 328 (C328) by the oxidative adduct malondialdehyde (MDA). Moreover, elevated levels of secreted MDA-modified vimentin were detected in the plasma of aged senescence-accelerated mouse prone 8 mice, which are known to have deregulated reactive oxygen species metabolism and accelerated aging. Based on these findings, we hypothesize that humoral innate immunity may recognize senescent cells by the presence of membrane-bound MDA-vimentin, presumably as part of a senescence eradication mechanism that may become impaired with age and result in senescent cell accumulation.
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Hendrickson, Jeanne E., Traci E. Chadwick, John D. Roback, Christopher D. Hillyer, and James C. Zimring. "Host Inflammation Increases Alloimmunization to Transfused Red Blood Cells." Blood 106, no. 11 (November 16, 2005): 1887. http://dx.doi.org/10.1182/blood.v106.11.1887.1887.
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Abstract Background: Alloimmunization to RBC is a serious sequelae of transfusion, which can result in hemolytic transfusion reactions and difficulty identifying compatible units for future transfusion. Although any given unit of RBC contains numerous alloantigens, only 6% of transfusion recipients mount a measurable alloantibody response. The factors that determine whether a given transfusion recipient will generate antibodies remains undetermined. Activation of the innate immune system through inflammation is known to have a significant effect on immune responses in other settings. Accordingly, we hypothesized that recipient inflammation would modulate humoral responses to transfused RBC. Methods: Hen egg lysozyme (HEL) is a well studied antigen. In order to convert HEL into a model blood group antigen, we utilized transgenic mHEL mice, which express HEL on the surface of RBC as a transmembrane protein. Leukoreduced mHEL RBC were transfused into B10. BR recipient mice (H-2k MHC haplotype). To induce host inflammation, recipient mice received an intraperitoneal injection of poly(I:C), which is a double-stranded RNA that mimics inflammation commonly seen with viral infection. The inflammatory effects of poly (I:C) were confirmed by observing activation of macrophages using flow cytometry. Plasma was obtained from recipient mice 7 and 14 days post-transfusion, and anti-HEL antibody titers and isotypes were determined by HEL specific ELISA. Results: Inflammation of mice with poly (I:C) resulted in a significant increase in the magnitude of anti-HEL IgG synthesis. Whereas mice receiving mHEL RBC alone had only a weak anti-HEL IgG response, treatment with poly (I:C) prior to transfusion resulted in a 15 fold increase in anti-HEL IgG (p value =.0003). In addition, whereas IgG1 and IgG3 were the predominant anti-HEL IgG subtypes in mice receiving mHEL RBC alone, IgG3 and IgG2b predominated in mice treated with poly (I:C) prior to mHEL transfusion. Thus, treatment of transfusion recipients with an agent that mimics inflammation commonly seen in viral infections significantly increased humoral immunity and altered IgG subtype composition. Discussion: The findings reported here demonstrate that host inflammation with a viral-like agent increases alloimmunization to transfused RBC and suggests that co-existing infections in humans may increase humoral immunization to transfused RBC. In addition, since different IgG subtypes have different hemolytic potentials, the observed deviation may influence the clinical significance of alloantibody formation. These findings provide the rational basis for possible intervention using immunomodulatory agents to prevent alloimmunization or to divert the response to a non-hemolytic IgG subtype.
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Buchbinder, Aby, Thomas Basile, Cliff Ding, Jeff Hester, Jing Yu, Thomas Eckhardt, Charles Conover, and Ivan Horak. "Evaluation of Ethnic Differences in Mannose-Binding Lectin (MBL) Level or MBL Genotype." Blood 108, no. 11 (November 16, 2006): 3859. http://dx.doi.org/10.1182/blood.v108.11.3859.3859.
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Abstract Background: MBL is a natural human plasma protein that plays an important role in the humoral innate immune defense. MBL specifically recognizes a broad range of microorganisms, including bacteria, fungi, viruses, and parasites, by binding to common carbohydrate structures located on their surfaces and activating the lectin pathway of complement. The concentration of MBL in plasma is largely genetically determined and ranges from 5 to 10,000 ng/mL. Deficiency is caused by mutations within the mbl2 gene or its promoter region. Individuals heterozygous (A/O) and homozygous (O/O) for these mutations display a reduced level of MBL in plasma. Low levels of MBL have been associated with increased risk of serious infection in situations in which other components of the immune system are compromised. Studies in patients with hematologic malignancies undergoing chemotherapy suggest that low MBL levels or variant MBL genotypes (A/O or O/O) are correlated with infectious complications of chemotherapy and/or duration of febrile neutropenia. The effect of ethnicity on MBL level and genotype was examined as part of the development of recombinant human MBL (rhMBL), a novel molecule that is entering clinical trials. Methods: The plasma MBL level (protein concentration) and MBL genotype of 80 healthy volunteers were determined by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. Results: No differences in MBL level or genotype were observed among the 3 ethnic groups (see table below). Overall, the plasma MBL level was <100 ng/mL for 10% of the volunteers and <300 ng/mL for 16%. Regarding MBL genotype, 4% had an O/O genotype and 34% had an A/O genotype. Conclusions: The MBL level and genotype data from 80 healthy volunteers of different ethnic backgrounds were observed to be generally concordant. Further analyses in individuals with other ethnicities are ongoing. MBL Level and MBL Genotype by Ethnicity White Black Hispanic Total (N=50) (N=15) (N=15) (N=80) n (%) n (%) n (%) n (%) MBL Level (ng/mL) <100 5 (10) 1 (7) 2 (13) 8 (10) 100 to <300 3 (6) 2 (13) 0 5 (6) ≥300 42 (84) 12 (80) 13 (87) 67 (84) MBL Genotype A/A 32 (64) 9 (60) 9 (60) 50 (63) A/O 16 (34) 6 (40) 5 (33) 27 (34) O/O 2 (4) 0 1 (7) 3 (4)
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Robertson, Louise J., Julie S. Moore, Kevin Blighe, Kok Yew Ng, Nigel Quinn, Fergal Jennings, Gary Warnock, et al. "Evaluation of the IgG antibody response to SARS CoV-2 infection and performance of a lateral flow immunoassay: cross-sectional and longitudinal analysis over 11 months." BMJ Open 11, no. 6 (June 2021): e048142. http://dx.doi.org/10.1136/bmjopen-2020-048142.
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ObjectiveTo evaluate the dynamics and longevity of the humoral immune response to SARS-CoV-2 infection and assess the performance of professional use of the UK-RTC AbC-19 Rapid Test lateral flow immunoassay (LFIA) for the target condition of SARS-CoV-2 spike protein IgG antibodies.DesignNationwide serological study.SettingNorthern Ireland, UK, May 2020–February 2021.ParticipantsPlasma samples were collected from a diverse cohort of individuals from the general public (n=279), Northern Ireland healthcare workers (n=195), pre-pandemic blood donations and research studies (n=223) and through a convalescent plasma programme (n=183). Plasma donors (n=101) were followed with sequential samples over 11 months post-symptom onset.Main outcome measuresSARS-CoV-2 antibody levels in plasma samples using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays over time. UK-RTC AbC-19 LFIA sensitivity and specificity, estimated using a three-reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples.ResultsWe detected persistence of SARS-CoV-2 IgG antibodies for up to 10 months post-infection, across a minimum of two laboratory immunoassays. On the known positive cohort, the UK-RTC AbC-19 LFIA showed a sensitivity of 97.58% (95.28% to 98.95%) and on known negatives, showed specificity of 99.59% (98.53 % to 99.95%).ConclusionsThrough comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting over 46 weeks when assessed by EuroImmun ELISA, providing insight to antibody levels at later time points post-infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 spike protein IgG antibody detection in a laboratory-based setting.
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Tovar, Natalia, Carlos Fernández de Larrea, Juan I. Aróstegui, María Teresa Cibeira, Laura Rosiñol, Montserrat Rovira, Montserrat Elena, Xavier Filella, Jordi Yagüe, and Joan Blade. "Characterization and Prognostic Impact of Oligoclonal Humoral Response in Patients with Multiple Myeloma After Autologous Stem-Cell Transplantation: Long-Term Results From a Single Institution." Blood 120, no. 21 (November 16, 2012): 3948. http://dx.doi.org/10.1182/blood.v120.21.3948.3948.
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Abstract Abstract 3948 Background: Multiple myeloma (MM) is characterized by the production of a monoclonal immunoglobulin of constant isotype and light chain restriction due to the clonal proliferation of neoplastic plasma cells. The optimal treatment in patients younger than 65 years includes induction therapy followed by high- dose therapy/autologous stem-cell transplantation (ASCT). On the other hand, the emergence of oligoclonal bands is a benign phenomenon frequently associated with complete remission (CR) after ASCT. The aim of the present study was to investigate the incidence, biological characteristics, duration and prognostic value of the oligoclonal bands in patients with MM who underwent ASCT at our institution in the last 18 years. Methods: Two-hundred and eleven patients underwent melphalan-based ASCT at our institution from March 31st, 1994, to December 27th, 2011. Of these, 199 patients (109M/90F; median age 55 years, range 25 to 70) who achieved at the least a partial response (PR) after ASCT are the basis of this study. Initial baseline demographics, clinical and laboratory data, and information concerning treatment and follow up were collected. No patient was lost to follow-up. The median follow-up for alive patients was 4.7 years (range 4 months to 18 years). A retrospective systematic review of all serum and urine immunofixation (IFE) studies was carried out. An oligoclonal humoral response was defined as the presence of a serum and/or urine IFE monoclonal spike different from the original myeloma protein either in heavy and/or light chains, as well as at IFE migration pattern. Response, relapse, and progression were defined according to European Blood and Marrow Transplantation (EBMT) criteria. Results: Median PFS was 87 out of the 199 patients (43.7%) achieved CR. The median progression-free survival (PFS) and overall survival (OS) after ASCT were 3.2 and 6.6 years, respectively. Oligoclonal bands were observed in 34% of the patients, but with different prevalence according to the use of novel agents vs. conventional chemotherapy (63% vs. 22%; p=0.0001) in induction. This phenomena was almost exclusive of patients in CR compared to other degrees of response (92% vs. 8%; p=0.0001). Five patients with IgA and five with Bence Jones MM were the only ones being in PR and having a very transient coexistence of the original M-protein with IgG oligoclonal bands in serum. The median number of different isotypes accounting for oligoclonal humoral response was 2 (range 1 to 6) and this phenomena lasted for a median of 1.35 years. Serum bands were more frequent (75.4%) than those in urine and the main involved serum heavy-chain was IgG (73%), with almost the same distribution kappa/lambda. Kappa light-chain was the predominant isotype in urine (60%). In the overall series, all the oligoclonal bands disappeared before serological and clinical progression, except in two settings. First, patients (n=6) who progressed with extramedullary disease with soft-tissue plasmacytomas without significant bone marrow or serological involvement, had persistent oligoclonal bands for several months. Second, patients with Bence Jones MM (n=6), showing urine M-protein progression at the time of relapse had also a transient persistence of serum oligoclonal bands. The presence of oligoclonal bands after ASCT resulted in a significantly longer PFS (p=0.004). This translated in a significantly longer OS in patients with this humoral oligoclonal response (median OS not reached vs. 5.58 years; p=0.003) (Figure 1). An oligoclonal humoral response stable more than one year after ASCT was associated with a significantly longer clinical PFS and OS than those with shorter duration (p=0.008 and p=0.0001, respectively). Of note, the estimated survival of patients with oligoclonal bands lasting for more than one year at 10 years is 70% (Figure 2). In contrast, the PFS ad OS of patients with oligoclonal bands lasting for less than one year were similar to those who never developed this phenomena. Conclusions: The emergence of oligoclonal bands after ASCT is a prognostic factor and it is usually observed in patients in CR. They reflect a robust humoral immune response and consequently an immune system reconstitution. Duration of this humoral response is also associated with a significant survival prolongation. Disclosures: No relevant conflicts of interest to declare.
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Rosenzweig, Michael A., Heather Landau, Achim A. Jungbluth, Nicole Hanson, Denise Frosina, Maria Arcila, Raymond L. Comenzo, and Guenther Koehne. "Cancer-Testis (CT) Antigen Expression In AL Amyloidosis." Blood 116, no. 21 (November 19, 2010): 4055. http://dx.doi.org/10.1182/blood.v116.21.4055.4055.
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Abstract Abstract 4055 Cancer-testis (CT) antigens are a family of proteins normally expressed in immune privileged sites such as testicular germ cells and placenta, but are overexpressed in various malignant tumors (Scanlan et al. Immunological Rev. 2002). CT antigens are therefore useful markers of malignancy as well as potential targets for antigen specific cancer immunotherapy. In multiple myeloma, CT 7, CT10 and MAGE-A are homogenously expressed in up to 75% of cases, and their expression increases with disease stage and cell proliferation (Jungbluth et al. Blood, 2005). In addition, CT-7 and MAGE-A3 play a role in plasma cell proliferation and chemosensitivity (Atanackovic et al. Haematologica 2010). Immunogenicity of CT antigens is evidenced by spontaneous humoral responses against CT antigens in patients with multiple myeloma (Cohen et al. ASH abstract 2008). In addition, anti-CT antigen immune responses of donor derived T and B cells have been reported following allogeneic stem cell transplantation, suggesting CT antigens may serve as a natural target for a graft-versus myeloma effect (Atanackovic et al. Blood 2007). Systemic light-chain (AL) amyloidosis is a plasma cell dyscrasia related to multiple myeloma characterized by small numbers of non-proliferating, clonogenic plasma cells producing pathologic light chains. In this study, we investigated the expression of several CT antigens in patients with AL amyloidosis to identify potential targets for immunotherapy and determine their prognostic significance. Methods: Fifteen cases of AL amyloidosis were studied employing standard IHC techniques on paraffin-embedded archival tissues. Presence of plasma cells was verified by CD138 immunostain. The following monoclonal antibodies (to the following CT Antigens) were used: mAb MA454 (MAGE-A1), 6C1 (several MAGE-A antigens), 57B (MAGE-A4), E978 (NY-ESO-1), CT7-33(CT7), CT10#5 (CT10), #26 (GAGE). Immunopositivity was graded based on the amount of IHC-positive plasma cells. Results: All 15 patients had a confirmed diagnosis of AL amyloidosis with an average plasma cell burden of 12.7% of the cells in the marrow. Eighty-seven percent (13/15) had lambda disease and 13% (2/15) kappa disease. Organ involvement included kidney (n=7)), heart (n=8), peripheral nervous system (n=2), and GI/liver (n=2). Five patients (33%) had multi-organ involvement. All patients were treated uniformly with risk-adapted melphalan as their initial therapy. CT7 was present in 9/15 (60%) while CT10 was demonstrated in only 1/15 AL amyloid cases. Plasma cells did not stain with any other anti-CT mAb. There were no significant differences with regard to organ involvement, response to treatment or prognosis and CT antigen positivity in this small sample set. Discussion: This is the first study identifying CT7 as the prevalent CT antigen in plasma cells of patients with AL amyloidosis. The almost exclusive presence of CT7 in AL amyloidosis may have clinical significance. Further studies are planned on additional samples to confirm the prevalence of CT7 expression in AL amyloidosis, determine its immunogenicity and further investigate prognostic implications. Additional studies are needed to determine the biology of CT antigens in AL amyloidosis and their value as a potential target for immunotherapy. Disclosures: Comenzo: Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Elan Pharmaceuticals: Consultancy; Genzyme: Research Funding; Celgene: Research Funding; Ortho: Research Funding.
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Zaitseva, N. V., M. A. Zemlianova, and Oleg V. Dolgikh. "GENOMIC, TRANSCRIPTOMIC AND PROTEOMIC TECHNOLOGIES AS A MODERN TOOL FOR HEALTH DISORDERS DIAGNOSTICS, ASSOCIATED WITH THE IMPACT OF ENVIRONMENTAL FACTORS." Hygiene and sanitation 99, no. 1 (January 15, 2020): 6–12. http://dx.doi.org/10.33029/0016-9900-2020-99-1-6-12.
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Introduction. Today, it is relevant to use modern critical technologies for identifying and evaluating the negative effects associated with the effects of chemicals at the stages of pre-nosological changes. This improves the efficiency of the early detection of progress in pre-pathological conditions prior to the onset of pronounced functional changes and the aggravation of the disease. The use of molecular diagnostic methods based on genomic, transcriptomic, and proteomic analysis technologies is one of the most promising approaches. Aim of the work is an analysis of both aspects and practical use of the modern critical technologies capabilities (genomic, transcriptomic and proteomic technologies) in the implementation of biomedical and experimental studies for the tasks of the detection biomarkers of negative effects of chemical risk factors on the example of exposure conditions with aluminum compounds. Material and methods. The proteomic analysis was carried out by the method of two-dimensional electrophoresis, polymorphism of alleles and genotypes of candidate genes by a real-time polymerase chain reaction. The transcriptome state was assessed based on the results of gene expression studies. The expression of membrane and serum proteins was studied by biochemical and immunological methods analysis. Statistical processing of the results was carried out in the systems “Gencalculator,” “Gene Expert” and online program “SNPStats”. Results. The results of using proteomic analysis technologies made it possible to identify proteins annexin-13, SH3-domain protein-RF3, cathepsin L1 and, accordingly, genes CTSL, SH3RF3, THO complex subunit 2 as Ohmic markers of aerogenic exposure of inorganic compounds. The results of the analysis of gene polymorphism in the population exposed to environmental pollution allowed establishing the changed frequency of variant alleles and genotypes of genes: immune control - TLR4 (toll-like receptor); vascular factors - eNOS rs1799983 (endothelial NOsintase); detoxification - coproporphyrinogen oxidase CPOX (rs1131857), cytochrome P450 CYP1A1 (rs 1048943); neuro-humoral regulation of ANKK1 rs1800497 (dopamine receptor gene) and HTR2A rs7997012 (serotonin receptor gene). The results of gene expression analysis made it possible to establish negative transcriptomic effects induced by exposure to amphoteric metals due to the isolation of specific CD4+, CD8+, CD16+ cell phenotypes expressing the proteomic profile gene of blood plasma lipoprotein A (LPA gene). Discussion. The obtained results correspond data of a number of scientific studies, noting the importance of identifying polymorphic deviations of genes determining the individual risk of health problems in a variety of stressful environmental factors affecting humans. Minor genotypes of candidate genes under conditions of excessive contamination with amphoteric metal compounds significantly increase the risk of deviations in immune regulation indices, which modifies apoptosis mechanisms, which are crucial for the formation of atopy and onco-proliferation. Conclusion. The use of genome, transcriptomic and proteomic technologies as a modern tool for the diagnostics of health disorders allowed justifying the set of priority exposition and effect Ohmic-markers, associated with aerogenic effect of amphoteric metals, which have a modifying effect on the pathogenetic mechanisms of the formation of disorders of nervous and immune systems, the 1st and 2nd phase of detoxification, the likelihood of vascular disorders and onco-proliferative processes.
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Sakamaki, Ippei, Beatrisa Kaplan, Soung-Chul Cha, Hong Qin, and Larry W. Kwak. "Potent Immunomodulatory Effects of Lenalidomide on Effector T Cells and Treg Improve the Effectiveness of a Therapeutic Lymphoma Vaccine." Blood 118, no. 21 (November 18, 2011): 108. http://dx.doi.org/10.1182/blood.v118.21.108.108.
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Abstract Abstract 108 Lenalidomide is an effective therapeutic agent with direct inhibitory effects on malignant B- and plasma cells and immunomodulatory effects on the tumor microenvironment. The dual functions of Lenalidomide make it an appealing candidate for combination with other novel agents for lymphoma and myeloma therapy. In this study, we investigated the immune stimulatory effects of Lenalidomide on the potency of a model lymphoma vaccine (MCP3-sFv). Therapeutic vaccines based on the idiotype of the clonal Ig receptor on malignant B cells have been shown previously to elicit specific immunity in human patients, and a recent controlled Phase III trial of an idiotype protein vaccine demonstrated prolongation of disease free survival in follicular lymphoma patients (J Clin Oncol. 10;29(20):2787–94 2011). In prophylactic experiments, the groups of 10 BALB/c mice immunized with a novel fusion DNA idiotype vaccine (MCP3-sFv, Science. 1;298(5595):1025–9 2002) were then treated with Lenalidomide at various doses (5–50 mg/kg) or saline as control i.p. for 35 consecutive days. This combination strategy protected mice from a lethal syngeneic A20 murine lymphoma, resulting in significantly improved survival comparing with vaccine or Lenalidomide alone or saline. Furthermore, more than 70% of surviving mice treated with the combination were resistant to tumor re-challenge suggesting memory antitumor immunity. Mechanistically, protection required effector cellular immunity, as tumor protection was abrogated by treatment of depleting antibody against CD8+ T cells, either alone or together with CD4 depleting antibody in vivo. Lenalidomide showed little impact on humoral immunity, with serum anti-idiotype antibody levels in the combination group similar to the vaccine alone group. In addition to adaptive immune system, we also examined the effect of Lenalidomide on other immune cells including NK cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). Interestingly, Lenalidomide treatment did not affect the number of these immune cell populations in non-tumor bearing mice; but in tumor-bearing mice, Lenalidomide-induced tumor regression was associated with reduced numbers of immune suppressive cells (MDSC/Treg) and rescue of circulating NK cells. This finding suggests a role of Lenalidomide in ameliorating tumor-induced immune suppression. This hypothesis was supported by the demonstration that the combination of Lenalidomide and vaccine (vaccine given starting on day 8) produced significantly improve survival, compared with controls receiving vaccine or Lenalidomide alone (log rank p<0.05). In conclusion, the opposing effects of Lenalidomide on enhancing cellular immunity and ameliorating immune suppression make it ideal for combination with active specific immunotherapy for treatment of hematological malignancies. Disclosures: Kwak: Biovest International, Antigenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biovest International: ; Antigenics, Xeme Biopharma: Equity Ownership.
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van Spriel, Annemiek B. "Tetraspanins in the humoral immune response." Biochemical Society Transactions 39, no. 2 (March 22, 2011): 512–17. http://dx.doi.org/10.1042/bst0390512.
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The tetraspanins represent a large superfamily of four-transmembrane proteins that are expressed on all nucleated cells. Tetraspanins play a prominent role in the organization of the plasma membrane by co-ordinating the spatial localization of transmembrane proteins and signalling molecules into ‘tetraspanin microdomains’. In immune cells, tetraspanins interact with key leucocyte receptors [including MHC molecules, integrins, CD4/CD8 and the BCR (B-cell receptor) complex] and as such can modulate leucocyte receptor activation and downstream signalling pathways. There is now ample evidence that tetraspanins on B-lymphocytes are important in controlling antibody production. The tetraspanin CD81 interacts with the BCR complex and is critical for CD19 expression and IgG production, whereas the tetraspanin CD37 inhibits IgA production and is important for IgG production. By contrast, the tetraspanins CD9, Tssc6 and CD151 appear dispensable for humoral immune responses. Thus individual tetraspanin family members have specific functions in B-cell biology, which is evidenced by recent studies in tetraspanin-deficient mice and humans. The present review focuses on tetraspanins expressed by B-lymphocytes and discusses novel insights into the function of tetraspanins in the humoral immune response.
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Khanna, Nina, Maja Weisser, Anemone Hedstueck, Sarah Tschudin Sutter, Sandra Roesch, Manuel Battegay, Laura Infanti, et al. "Efficacy of COVID-19 Pathogen Inactivated Convalescent Plasma for Patients with Moderate to Severe Acute COVID-19: A Case Matched Control Study." Blood 136, Supplement 1 (November 5, 2020): 29–30. http://dx.doi.org/10.1182/blood-2020-136180.
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Background. COVID-19, caused by the SARS-CoV-2 virus, is a pandemic disease with high morbidity and mortality. Currently, available therapeutic options for COVID-19 are limited. Prior experience in epidemics with convalescent plasma (CP) containing antibodies to viruses has demonstrated variable indications of therapeutic efficacy for: Influenza, Argentine Hemorrhagic Fever, and SARS. Characterizing antibody titers to viruses has indicated correlation with therapeutic efficacy. Convalescent COVID-19 patients with potent SARS-CoV-2 antibody responses can serve as plasma donors for immune therapy. However, antibody responses are variable, many donors are first-time higher risk blood donors, and rapid assays to select optimal CP immune efficacy are limited. Pathogen inactivation (PI) of CP can reduce the risk of transfusion-transmitted infection by unrecognized pathogens. Objectives. This study characterized COVID-19 PI-CP activity; and evaluated efficacy and safety of PI CP transfusion in a case matched controlled cohort of acute COVID-19 patients. Methods. COVID-19 apheresis CP (650 - 1300 mL) was collected from nasopharyngeal PCR + outpatients following 2 PCR negative tests or 28 days after symptom resolution. Amotosalen-UVA PI of CP (INTERCEPT Blood System for Plasma) was performed, and antibody efficacy before and after PI was characterized by: VSV reporter pseudo-virus plaque neutralization (RVPN) NT-50 titer (Vitalant Research Institute, San Francisco), antibody to S and N virus proteins by agglutination-dependent antibody PCR (ADAP, Enable Biosciences, San Francisco), virus ACE-2 soluble receptor neutralization assay (Enable Biosciences), and SARS-CoV-2 antibody profile by coronavirus microarray (University of California, Irvine). Patient inclusion criteria were: confirmed SARS-CoV-2 infection, hospitalization, pulmonary infiltrates, availability of ABO compatible CP, and informed consent. CP patients were matched with control patients (CTRL) for disease severity at diagnosis by standardized clinical risk score (W. Liang et al JAMA Intern Med 2020) and concomitant Tocilizumab use. CP Patients received a total of 400 mL of PI CP from 2 donors over 48 hours and standard therapy. CTRL patients received standard COVID-19 therapy without CP. The primary outcome was in-hospital death to day 28. Secondary outcomes included: progression to intubation, admission to ICU, time to discharge, serious adverse events, NP viral clearance, plasma viral clearance, and humoral immune responses. Differences between CP and CTRL patients were assessed by the Mann-Whitney test for continuous variables, and by Fisher's exact test for categorical variables. Progression to ICU and intubation were analyzed as odds ratios calculated by conditional logistic regression. Results. 15 CP and 30 CTRL patients were enrolled. One CP patient was admitted in cardiogenic shock. Only 2 of 15 CP cohort patients had detectable IgG antibody to SARS CoV-2 S1 antigen at study entry. 3 of 15 PI CP donors had negligible SARS CoV-2 IgG antibodies to all antigens, and demonstrated poor neutralization efficacy. 12/15 CP had effective RVPN titers (> 1:80), RVPN titers were correlated with ACE-2 neutralization antibody titers (r2 = 0.83), and had significant activity specific for S and RBD antigens by microarray profiling (Figure 1). SARS CoV-2 antibody levels were variable between CP donors, but not impacted by PI (Figure 1). Baseline characteristics of CP and matched CTRL patients were similar (Table 1). Sensitivity analysis was performed assessing mortality after exclusion of one CTRL patient admitted in cardiogenic shock and the 2 respective controls. In-hospital 28-day mortality was lower in the CP cohort (0/14) compared to 5/28 CTRL, p = 0.151, 2-sided Fisher's exact test. Progression to intubation, ICU admission, and days in hospital were not significantly different (Table 1). There was a trend toward decreased inflammatory response (CRP normalization) in CP patients. Conclusions. In hospital mortality of COVID-19 patients was lower in the PI-CP cohort, but not statistically significant. 15% of CP had ineffective antibody by multiple assays. However, PI did not impact CP anti-SARS-CoV-2 activity. PI of plasma provides reduced risk of transfusion transmitted infection from COVID-19 CP donors. In this study, PI CP was safe, and may be effective for early treatment of hospitalized COVID-19 patients. Disclosures von Goetz: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Khan:Nanommune Inc.: Current equity holder in private company. Tsai:Enable Biosciences: Current Employment. Robinson:Enable Biosciences: Current Employment. Seftel:Enable Biosciences: Current Employment, Current equity holder in private company. Bagri:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.
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Tschumper, Renee C., Collin A. Osborne, Pritha Chanana, Jaime I. Davila, Denise K. Walters, Dominique B. Hoelzinger, and Diane F. Jelinek. "RNA-Seq Based Immunoglobulin Repertoire Analysis of Normal Plasma Cells Generated in an in Vitro B Cell Differentiation System." Blood 134, Supplement_1 (November 13, 2019): 1051. http://dx.doi.org/10.1182/blood-2019-127327.
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Antibody secreting plasma cells (PCs) play an important role in effective humoral immune responses. The low frequency of bone marrow PCs in humans makes it challenging to obtain sufficient numbers of PCs for biologic studies. Previous studies have employed in vitro model systems to generate cells that morphologically, phenotypically, and functionally resemble normal polyclonal PCs. Gene expression profiles of in vitro generated PCs (IVPCs) mirror their normal counterparts, however to date extensive immunoglobulin (Ig) repertoire analysis of IVPCs is lacking. Here, we used a modified 3-step protocol to generate IVPCs and used RNA-seq to explore the transcriptome with emphasis on the Ig repertoire of plasmablasts and PCs. Total B cells were isolated from 3 normal donors and cultured with various cytokines and the B cell activators CpG ODN and CD40L. RNA was obtained from freshly isolated B cells (Day 0; D0) as well as from Day 4 (D4) plasmablasts, and Day 10 (D10) IVPCs. Morphologically, D10 cells exhibited typical PC morphology, including an eccentric nucleus and perinuclear hof. RNA-seq was performed on total RNA from all 3 donors and time points using the Standard TRuSeq v2 library prep and with paired end sequencing on the Illumina HiSeq 4000 platform. Principle component analysis of gene expression data showed that D0, D4 and D10 cells could be clearly segregated across all 3 normal donors. Of importance, transcripts previously described as distinguishing B cells from PCs were found to be differentially expressed including overexpression of CXCR5, CD19, EBF, CD83, PAX5, IRF8 in D0 B cells and overexpression of IRF4, Blimp-1, XBP1, BCMA, SLAMF7, Syndecan-1, CD38 and CD27 in IVPCs, thus validating our in vitro model for generating PCs. Furthermore, expression of cell cycle related transcripts such as CKS1, CDK1, and CCDN2 followed the pattern of low expression in resting B cells, increased expression in plasmablasts, and decreased expression in IVPCs confirming the cells are actively cycling in a manner comparable to cells in vivo. D10 IVPCs also overexpressed transcripts known to be upregulated during the unfolded protein response. As expected from Ig secreting cells, D10 IVPCs had an over-representation of Ig transcripts. At D0, resting B cells had high levels of IgD and IgM heavy chain (HC) transcripts. At D10, IgM transcripts modestly increased with Log2 fold change (FC) = 3 and as expected, IgD levels decreased significantly (Log2 FC = -2.2). IgA and IgG isotype transcripts significantly increased at D10 (Log2 FC > 6.0) with the IgG4 subtype having the greatest Log2 FC at 8.4. Next we focused on the Ig repertoire of D0, D4, and D10 cells. By aligning to known germline Ig sequences in IMGT/V-Quest (www.imgt.org) and then assembling the paired ends of D0, D4 and D10 Ig transcripts, we were able to analyze the Ig repertoire. Since the Ig HC variable (V) region is encoded by V, diversity (D) and joining (J) segments, only fragments that could be confidently determined were considered. All but 3 IGHV transcripts (IGHV3-35, IGHV3-47 and IGHV7-8) and 2 IGHD transcripts (IGHD4-4 and IGHD5-5) were found and all IGHJ segments were represented across the differentiation spectrum. In D0 cells, the number of unique VDJ combinations ranged from 643 to 863 across all 3 normal samples and increased to a range of 2524 to 2867 in D10 IVPCs. When looking at the differential expression of each VDJ combination from D0 to D10, a pairwise t-test for relative frequency showed that there was no significant change greater than 1%, suggesting the repertoire diversity was not skewed, thus proving the conditions for stimulation were not targeting any one starting B cell. Our data also allowed us to track clonal expansions during differentiation as defined by the increasing frequency of sequences with identical nucleotide sequence in the V region and CDR3 (including D and J regions). Hence, a single sequence could be tracked from D0 to D10. Of interest, in a small sampling of the total available sequences, only those B cells with a mutated IGHV region, characteristic of a memory B cell, went on to expand in this system whereas B cells with an unmutated IGHV did not. Our analysis of the Ig repertoire of IVPCs suggests this system provides a functional model to study Ig repertoire along the B cell differentiation process and further delineate the conditions that may result in a clonal expansion, a hallmark of many hematologic malignancies including multiple myeloma. Disclosures No relevant conflicts of interest to declare.
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Peters, Iain R., Chris R. Helps, Timothy J. Gruffydd-Jones, Michael J. Day, and Séverine Tasker. "Antigen Specificity of the Humoral Immune Response to Mycoplasma haemofelis Infection." Clinical and Vaccine Immunology 17, no. 8 (June 2, 2010): 1238–43. http://dx.doi.org/10.1128/cvi.00136-10.
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ABSTRACT The aim of the present study was to characterize the antigenic specificity of the humoral immune response made by cats infected with the feline hemoplasma, Mycoplasma haemofelis. A crude M. haemofelis antigen preparation was prepared from red blood cells (RBCs) collected from a cat at the time of a high level of bacteremia. Plasma samples were collected from six cats before and after experimental infection with M. haemofelis, with regular sampling being performed from 15 to 149 or 153 days postinfection (dpi). Preinfection RBC membrane ghosts were prepared from these six cats and used to identify erythrocyte proteins that may have contaminated the M. haemofelis antigen preparation. The M. haemofelis antigen preparation comprised 11 protein bands. The immunodominant bands on Western blotting with infected cat plasma had molecular masses of 78, 68, 60, 48, and 38 kDa. Most cats (n = 5) had plasma antibody that reacted with at least one band (always including the one of 68 kDa) at 15 dpi, and all cats were seroreactive by 29 dpi. The maximum number of antibodies from an individual animal specific for an antigen was identified in plasma collected from 57 to 99 dpi. Contamination of the M. haemofelis antigen preparation with RBC membrane proteins was observed. The contaminating RBC proteins had molecular masses of from 71 to 72 kDa (consistent with band 4.2) and 261 and 238 kDa (consistent with spectrin), and these were recognized by all plasma samples. A range of M. haemofelis antigens is recognized by cats infected experimentally with the organism. These represent possible targets for immunoassays, but care must be taken to prevent false-positive results due to host protein contamination.
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AHMAD, WASEEM, and AJIT NARAYANAN. "HUMORAL ARTIFICIAL IMMUNE SYSTEM (HAIS) FOR SUPERVISED LEARNING." International Journal of Computational Intelligence and Applications 11, no. 01 (March 2012): 1250004. http://dx.doi.org/10.1142/s1469026812500046.
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Nature over millions of years has found innovative, robust and effective methods through evolution for helping organisms deal with the challenges they face when attempting to survive in hostile and uncertain environments. Two critical natural mechanisms in this evolutionary process are variation and selection, which form the basis of "evolutionary computing" (EC). EC has proved successful when dealing with complex problems, such as classification, clustering and optimization. In recent years, as our knowledge of microbiology has deepened, researchers have turned to micro-level biology for inspiration to help solve complex problems. This paper describes a novel supervised learning algorithm inspired by the humoral mediated response triggered by the adaptive immune system. The proposed algorithm uses core immune system concepts such as memory cells, plasma cells and B-cells as well as parameters and processes inspired by our knowledge of the microbiology of immune systems, such as negative clonal selection and affinity thresholds. In particular, we show how local and global similarity based measures based on affinity threshold can help to avoid over-fitting data. The novelty of the proposed algorithm is discussed in the context of existing immune system-based supervised learning algorithms. The performance of the proposed algorithm is tested on well-known benchmarked real world datasets and the results indicate performance not worse than existing techniques in most cases and improvement over previously reported results in some. The role of memory cells is highlighted as a key feature in AIS-based supervised learning that deserves further exploration and evaluation.
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Makhneva, Natalie V. "Cellular and humoral components of the immune system of the skin." Russian Journal of Skin and Venereal Diseases 19, no. 1 (February 15, 2016): 12–17. http://dx.doi.org/10.18821/1560-9588-2016-19-1-12-17.
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Along with mucous membranes the skin as the main barrier to the outside world creates a system of protection against any influences of the world. It is not only the place of realization of immunological processes, but it also actively participates in them due to the existence of its own elements of the immune system which are able to actively participate in the development of inflammatory reactions and neoplastic processes. Skin cells interact with cells of the immune system by setting a direct contact or by secreting a number of soluble factors, called cytokines, and other protein components such as proteins of the complement system. The general concept of skin-associated lymphoid tissue and skin’s immune system with immunocompetent cells in the epidermis and dermis, for cooperation of which in various stages of the immune response requires identity concerning anti-genes of HLA system, is presented in the review. Thus, specific immunological reaction with antibody formation promote the release of antigen from the body of both exogenous and endogenous origin. However, at violation of any element of immunological protection there is a delay of antigen elimination process, that results in own tissue structural damage. Interaction with foreign antigens (physical, chemical, infectious, etc.), denaturation of its own proteins or disclosure of tissue structures (antigens), that did not contact with immunocompetent cells, promote the formation of autoantigens and the production of autoantibodies against them. Thus, skin is a highly organized structure with a network of immunocompetent cells and soluble mediators. Introduction of molecular and biological methods as a knowledge tool is continually expanding the information about the skin as an organ of the immune system. The gained knowledge will definitely promote the development of new therapeutic approaches to skin diseases.
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Lendvai, Nikoletta, Sacha Gnjatic, Erika Ritter, Yao-Tseng Chen, Christina Coughlin, Robert H. Vonderheide, Ruben Niesvizky, et al. "Host Immune Responses Against CT Antigens in Multiple Myeloma Patients." Blood 108, no. 11 (November 16, 2006): 3492. http://dx.doi.org/10.1182/blood.v108.11.3492.3492.
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Abstract The type I Melanoma Antigen GEne (MAGE) proteins belong to the Cancer-Testis (CT) family of tumor-associated antigens and are widely expressed in solid and hematologic malignancies. They are immunogenic and frequently elicit spontaneous immune responses in patients with CT antigen-expressing tumors, particularly in malignant melanoma. In melanoma patients, there is high concordance between humoral and cellular immunity. Based on these findings, CT antigens are widely investigated as potential antigenic targets for tumor-specific therapeutic vaccines. We previously showed that the type I MAGE proteins CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A3 were commonly detected in primary myeloma specimens, and expression of CT7 and MAGE-A3 was correlated with abnormally elevated plasma cell proliferation. These findings suggest that type I MAGE may be rational targets for vaccine therapy in multiple myeloma. Therefore, it is important to determine if type I MAGE elicit cellular or humoral immune responses in myeloma patients. To investigate this hypothesis, we assessed cellular immunity against CT7 and humoral immunity against a broad panel of CT antigens. To quantify CT7-specific cellular immunity, expanded, polyclonal pools of T cells from the bone marrow, the tumor microenvironment, were co-cultured in interferon gamma (IFNγ) ELISpot assays with autologous antigen-presenting cells (APC) transduced with in vitro transcribed mRNA coding for CT7 or control antigens. CT antigen-specific humoral immunity was examined by ELISA assay using patient serum or plasma and recombinant CT antigens. This analysis demonstrated that 2/9 patients exhibited specific T cell immunity against CT7 in their bone marrow lymphocytes as measured by IFNγ secretion. These same two patients had positive titers for other CT antigens; one for MAGE-A1 (another type I MAGE), the other for SSX-1 (a structurally distinct CT antigen). Interestingly, neither patient had positive serology for CT7. Serum from 16 other myeloma patients did not have detectible antibody titers for a broad panel of CT antigens. These results show that CT antigens are immunogenic in myeloma patients, with cellular responses against CT7 and humoral responses against MAGE-A1 and SSX-1. However, unlike other types of cancer, there appears to be discordance between humoral and cellular immunity against CT7 in multiple myeloma. This may be due in part to the significant derangements of humoral immunity in this disease. These results support further investigation of immunologic therapies targeting type I MAGE in myeloma, especially therapeutic vaccine strategies.
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López, Barriga, Lorente, and Mir. "Immunoproteomic Lessons for Human Respiratory Syncytial Virus Vaccine Design." Journal of Clinical Medicine 8, no. 4 (April 10, 2019): 486. http://dx.doi.org/10.3390/jcm8040486.
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Accurate antiviral humoral and cellular immune responses require prior recognition of antigenic peptides presented by human leukocyte antigen (HLA) class I and II molecules on the surface of antigen-presenting cells. Both the helper and the cytotoxic immune responses are critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, which is a significant cause of morbidity and mortality in infected pediatric, immunocompromised and elderly populations. In this article we review the immunoproteomics studies which have defined the general antigen processing and presentation rules that determine both the immunoprevalence and the immunodominance of the cellular immune response to HRSV. Mass spectrometry and functional analyses have shown that the HLA class I and II cellular immune responses against HRSV are mainly focused on three viral proteins: fusion, matrix, and nucleoprotein. Thus, these studies have important implications for vaccine development against this virus, since a vaccine construct including these three relevant HRSV proteins could efficiently stimulate the major components of the adaptive immune system: humoral, helper, and cytotoxic effector immune responses.
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Maloney, M. D., and C. A. Lingwood. "CD19 has a potential CD77 (globotriaosyl ceramide)-binding site with sequence similarity to verotoxin B-subunits: implications of molecular mimicry for B cell adhesion and enterohemorrhagic Escherichia coli pathogenesis." Journal of Experimental Medicine 180, no. 1 (July 1, 1994): 191–201. http://dx.doi.org/10.1084/jem.180.1.191.
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The glycosphingolipid globotriaosyl ceramide (CD77) and other globo-series glycolipids containing terminal galactose (Gal)alpha 1-4Gal residues function as receptors for the verotoxin (Shiga-like toxin) family of Escherichia coli-elaborated toxins. CD77 is also a marker for germinal center B lymphocytes and Burkitt's lymphoma cells. The pan B cell marker CD19 is a 95-kD membrane protein that appears early in B cell differentiation and is only lost upon terminal differentiation to plasma cells. CD19 is involved in signal transduction and has a regulatory role in B cell proliferation and differentiation in response to activation in vitro. However, an endogenous ligand for CD19 has not yet been identified. We report herein that the extracellular domain of CD19 has a potential CD77-binding site with extensive sequence similarity to the verotoxin B-subunits. These B-subunit-like sequences on CD19 are in close proximity following the organization of intervening amino acids into disulfide-linked domains. Cocapping of CD19 and CD77 on Burkitt's lymphoma-derived Daudi cells with anti-CD19 antibodies indicates that CD19 and CD77 are associated on the B cell surface. Cell surface binding of anti-CD19 antibodies is decreased on CD77-deficient mutant Daudi cells, suggesting that CD77 expression influences the surface expression of CD19. Wild-type Daudi cells, but not the CD19/CD77-deficient mutants, bind to matrices expressing the carbohydrate moiety of CD77 or other Gal alpha 1-4Gal containing glycolipids. This binding can be inhibited by anti-CD77 antibodies, the CD77-binding verotoxin B-subunit or anti-CD19 antibodies. Daudi cells exhibit a degree of spontaneous homotypic adhesion in culture while the CD77/CD19-deficient Daudi mutants grow as single cells. The stronger homotypic adhesion that occurs in B cells after antibody ligation of CD19 and that involves, to some extent, the integrin system, is also dramatically lower in the mutant cells relative to the parent cell line. However, reconstitution of mutant cells with CD77 restores the anti-CD19 mAb-induced adhesion to wild-type Daudi cell levels. These studies represent the first time that CD19-mediated signaling has been reconstituted in a low-responder B cell line. These convergent observations provide compelling evidence that CD19/CD77 interactions function in adhesion and signal transduction at a specific stage in B cell development and suggest that such interactions have a role in B lymphocyte homing and germinal center formation in vivo. By targeting CD77+ B cells, verotoxins may suppress the humoral arm of the immune response during infection.(ABSTRACT TRUNCATED AT 400 WORDS)
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D’Amico, V. L., M. G. Palacios, and M. Bertellotti. "Antihelminthic treatment alters cellular but not humoral immune components in Magellanic Penguin (Spheniscus magellanicus) chicks." Canadian Journal of Zoology 96, no. 5 (May 2018): 447–53. http://dx.doi.org/10.1139/cjz-2017-0147.
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We evaluate whether helminth parasites affect both cellular and humoral components of the immune system of Magellanic Penguin (Spheniscus magellanicus (J.R. Forster, 1781)) chicks. We measured immune components after the administration of an antihelminthic drug to remove parasites. Cellular immune components included the complete white blood cell (WBC) count and the in vivo skin-swelling response to phytohemagglutinin (PHA). Humoral aspects assessed were the ability of plasma to agglutinate foreign particles and the bactericidal capacity of plasma. Antihelminthic treatment resulted in lower total WBC counts supporting the role of circulating leukocytes in fighting macroparasites. Deparasitized chicks showed a reduction in all types of leukocytes. Contrary to our expectation, deparasitized Magellanic Penguin chicks showed lower response to PHA injection than control chicks. The swelling response was positively correlated with body condition and with total WBC in circulation. We hypothesize that the specific helminth community naturally occurring in Magellanic Penguin chicks might have an overall immunostimulatory effect on the PHA response. Antihelminthic treatment did not alter the innate humoral immune parameters measured. Our results support the prediction that, given their relatively low costs of use and maintenance, innate humoral components would not be as affected by antihelminthic treatment as more costly cellular responses.
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Kim, Ki-Hye, Young-Man Kwon, Young-Tae Lee, Min-Chul Kim, Hye Hwang, Eun-Ju Ko, Youri Lee, Hyo-Jick Choi, and Sang-Moo Kang. "Virus-Like Particles Are a Superior Platform for Presenting M2e Epitopes to Prime Humoral and Cellular Immunity against Influenza Virus." Vaccines 6, no. 4 (September 20, 2018): 66. http://dx.doi.org/10.3390/vaccines6040066.
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Influenza virus M2 protein has a highly conserved ectodomain (M2e) as a cross-protective antigenic target. We investigated the antigenic and immunogenic properties of tandem repeat M2e (5xM2e) proteins and virus-like particles (5xM2e VLP) to better understand how VLP and protein platform vaccines induce innate and protective adaptive immune responses. Despite the high antigenic properties of 5xM2e proteins, the 5xM2e VLP was superior to 5xM2e proteins in inducing IgG2a isotype antibodies, T cell responses, plasma cells and germinal center B cells as well as in conferring cross protection. Mice primed with 5xM2e VLP were found to be highly responsive to 5xM2e protein boost, overcoming the low immunogenicity and protective efficacy of 5xM2e proteins. Immunogenic differences between VLPs and proteins in priming immune responses might be due to an intrinsic ability of 5xM2e VLP to stimulate dendritic cells secreting T helper type 1 (Th1) cytokines. We also found that 5xM2e VLP was effective in inducing inflammatory cytokines and chemokines, and in recruiting macrophages, monocytes, neutrophils, and CD11b+ dendritic cells at the injection site. Therefore, this study provides evidence that 5xM2e VLP is an effective vaccine platform, inducing cross-protection by stimulating innate and adaptive immune responses.
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von Mensdorff-Pouilly, S., F. G. M. Snijdewint, A. A. Verstraeten, R. H. M. Verheijen, and P. Kenemans. "Human MUC1 Mucin: A Multifaceted Glycoprotein." International Journal of Biological Markers 15, no. 4 (October 2000): 343–56. http://dx.doi.org/10.1177/172460080001500413.
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Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of the ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer progression represents two sides of one coin: on the one hand, loss of polarity and overexpression of MUC1 in cancer cells interferes with cell adhesion and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in essence a self-antigen, is displaced and altered in malignancy and induces immune responses. Tumor-associated MUC1 has short carbohydrate sidechains and exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellular immune responses. Natural antibodies to MUC1 present in the circulation of cancer patients may be beneficial to the patient by restricting tumor growth and dissemination: early stage breast cancer patients with a humoral response to MUC1 have a better disease-specific survival. Several MUC1 peptide vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominantly humoral responses to the antigen, but evidence that these immune responses may be effective against the tumor in humans is still scarce.
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Dewerchin, Hannah L., Els Cornelissen, and Hans J. Nauwynck. "Feline infectious peritonitis virus-infected monocytes internalize viral membrane-bound proteins upon antibody addition." Journal of General Virology 87, no. 6 (June 1, 2006): 1685–90. http://dx.doi.org/10.1099/vir.0.81692-0.
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Feline infectious peritonitis virus (FIPV) may cause a highly lethal infection in cats, in spite of a usually strong humoral immune response. Antibodies seem unable to identify infected cells and mediate antibody-dependent cell lysis. In this study, the effect of antibodies on Feline coronavirus (FCoV)-infected monocytes was investigated. Upon addition of FCoV-specific antibodies, surface-expressed viral proteins were internalized through a highly efficient process, resulting in cells without visually detectable viral proteins on their plasma membrane. The internalization was also induced by mAbs against the Spike and Membrane proteins, suggesting that both proteins play a role in the process. The internalization did not occur spontaneously, as it was not observed in cells incubated with medium or non-specific antibodies. Further, the internalization could not be reproduced in feline cell lines, indicating its cell-type specificity. This study sheds new light on the immune-evasive nature of FIPV infections.
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Krutikov, E. S., and V. A. Zhitova. "Factors of immune protection in the pathogenesis of urinary infections (literature review)." Nephrology (Saint-Petersburg) 24, no. 5 (August 31, 2020): 9–17. http://dx.doi.org/10.36485/1561-6274-2020-24-5-9-17.
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In recent years, ideas about the pathogenesis of urinary tract infections have been changed significantly. Various pathogenetic factors of microorganisms and new defense mechanisms against them have been discovered. A significant part of pathogens is inactivated by the first line of defense - innate immunity which includes epithelial barriers (mucous membranes), cellular (phagocytes, dendritic cells, NK-cells) and humoral (chemokines, cytokines, complement) components, as well as antimicrobial proteins). The second and more specific line of defense is the acquired (adaptive) immune system - humoral (B-cells, antibodies) immunity and cellular (T-cells) immunity. However, epithelial cells play an important role in the immune response. These cells interact with the components of both innate immunity and acquired one. Antimicrobial proteins are one of the most ancient and primitive components of the immune system and they are very widely spread in nature. More than 800 antimicrobial proteins have been described and more than 100 of them have been found in the human body. The mechanism of these proteins is mainly connected with the violation of the bacterial membrane integrity. Nevertheless, some proteins can inhibit protein and/or DNA synthesis. The most common protein in the urine is uromodulin (Tamm-Horsfall protein), synthesized in the thick ascending section of the Henle loop. Uromodulin does not have direct antimicrobial activity, but it is involved in the pathogenesis of many inflammatory kidney diseases. In addition, uromodulin acting through the TLR4 signaling pathway promotes the maturation of dendritic cells, thereby further activating innate and acquired immunity. Currently, the role of antimicrobial proteins and dendritic cells in the pathogenesis of the infectious process is being actively studied. It will probably have a significant practical value. Thus, the development of urinary tract infections is the process of competing for the interaction of the uropathogenic and the macroorganism. The treatment of these diseases (especially chronic) should not be limited to the use of antibacterial drugs. An important component of the pathogen eradication is to increase the activity of its own protective mechanisms.
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Kuenzle, Sandra, Hans-Christian von Büdingen, Mirjam Meier, Melanie D. Harrer, Eduard Urich, Burkhard Becher, and Norbert Goebels. "Pathogen Specificity and Autoimmunity Are Distinct Features of Antigen-Driven Immune Responses in Neuroborreliosis." Infection and Immunity 75, no. 8 (May 21, 2007): 3842–47. http://dx.doi.org/10.1128/iai.00260-07.
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ABSTRACT Neuroborreliosis (NB) is a chronic infectious disease of the central nervous system (CNS) caused by a tick-borne spirochete, Borrelia burgdorferi. In addition to direct effects of the causative infectious agent, additional immunity-mediated mechanisms are thought to play a role in the CNS pathology of NB. In order to further understand the involvement of humoral immune mechanisms in NB, we dissected the intrathecal antibody responses down to the single-plasma-cell level. Starting with single-cell reverse transcription-PCR of fluorescence-activated cell sorter-sorted cerebrospinal fluid plasma cells from an NB patient, we identified expanded clones and resurrected the antigen specificity of their secreted antibodies through recombinant expression of the correctly paired immunoglobulin heavy- and light-chain genes as monoclonal antibodies (MAbs). As expected, we found specificity for the causative infectious agent, B. burgdorferi, among the clonally expanded plasma cell (cePC)-derived MAbs. However, from an independent cePC of the same patient, we could derive MAbs specific for human CNS myelin, without detectable cross-reactivity with B. burgdorferi antigens. While reactivity against B. burgdorferi is a known feature of humoral immune responses in NB, we show (i) that immune responses specific for self antigens may be a distinct feature of CNS infections independent of pathogen reactivity and (ii) that humoral autoimmunity in NB (since found in cePC) is the result of a truly antigen-driven immune response. Our findings indicate that in NB mechanisms may be at play that induce distinct immune responses specific for pathogen and self antigens independent from “molecular mimicry.”
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Douglas, A. E., S. Bouvaine, and R. R. Russell. "How the insect immune system interacts with an obligate symbiotic bacterium." Proceedings of the Royal Society B: Biological Sciences 278, no. 1704 (August 18, 2010): 333–38. http://dx.doi.org/10.1098/rspb.2010.1563.
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The animal immune system provides defence against microbial infection, and the evolution of certain animal–microbial symbioses is predicted to involve adaptive changes in the host immune system to accommodate the microbial partner. For example, the reduced humoral immune system in the pea aphid Acyrthosiphon pisum , including an apparently non-functional immune deficiency (IMD) signalling pathway and absence of peptidoglycan recognition proteins (PGRPs), has been suggested to be an adaptation for the symbiosis with the bacterium Buchnera aphidicola . To investigate this hypothesis, the interaction between Buchnera and non-host cells, specifically cultured Drosophila S2 cells, was investigated. Microarray analysis of the gene expression pattern in S2 cells indicated that Buchnera triggered an immune response, including upregulated expression of genes for antimicrobial peptides via the IMD pathway with the PGRP-LC as receptor. Buchnera cells were readily taken up by S2 cells, but were subsequently eliminated over 1–2 days. These data suggest that Buchnera induces in non-host cells a defensive immune response that is deficient in its host. They support the proposed contribution of the Buchnera symbiosis to the evolution of the apparently reduced immune function in the aphid host.
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Uribe, C., H. Folch, R. Enriquez, and G. Moran. " Innate and adaptive immunity in teleost fish: a review." Veterinární Medicína 56, No. 10 (November 11, 2011): 486–503. http://dx.doi.org/10.17221/3294-vetmed.
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The immune system of fish is very similar to vertebrates, although there are some important differences. Fish are free-living organisms from the embryonic stage of life in their aquatic environment. They have mechanisms to protect themselves from a wide variety of microorganisms. Consequently, fish rely on their innate immune system for an extended period of time, beginning at the early stages of embryogenesis. The components of the innate immune response are divided into physical, cellular and humoral factors and include humoral and cellular receptor molecules that are soluble in plasma and other body fluids. The lymphoid organs found in fish include the thymus, spleen and kidney. Immunoglobulins are the principal components of the immune response against pathogenic organisms. Immunomodulatory products, including nucleotides, glucans and probiotics, are increasingly used in aquaculture production. The use of these products reduces the need for therapeutic treatments, enhances the effects of vaccines and, in turn, improves the indicators of production. The aim of this review is to provide a review of the immune system in fish, including the ontogeny, mechanisms of unspecific and acquired immunity and the action of some immunomodulators.
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Alcaraz, Carlos, Alberto Alvarez, and JoséM Escribano. "Flow cytometric analysis of African swine fever virus-induced plasma membrane proteins and their humoral immune response in infected pigs." Virology 189, no. 1 (July 1992): 266–73. http://dx.doi.org/10.1016/0042-6822(92)90702-q.
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Girish, C., and T. Smith. "Impact of feed-borne mycotoxins on avian cell-mediated and humoral immune responses." World Mycotoxin Journal 1, no. 2 (May 1, 2008): 105–21. http://dx.doi.org/10.3920/wmj2008.1015.
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Mycotoxins of economic importance in poultry production are mainly produced by Aspergillus, Penicillium and Fusarium fungi. The important mycotoxins in poultry production are aflatoxins, ochratoxins, trichothecenes, zearalenone and fumonisins. Mycotoxins exert their immunotoxic effects through various mechanisms which are manifested as reduced response of the immune system. Mycotoxin-induced immunosuppression in poultry may be manifested as decreased antibody production to antigens (e.g. sheep red blood cells) and impaired delayed hypersensitivity response (e.g. dinitrochlorobenzene), reduction in systemic bacterial clearance (e.g. Salmonella, Brucella, Listeria and Escherichia), lymphocyte proliferation (response to mitogens), macrophage phagocytotic ability, and alterations in CD4+/CD8+ ratio, immune organ weights (spleen, thymus and bursa of Fabricius), and histological changes (lymphocyte depletion, degeneration and necrosis). Mycotoxins, especially fumonisin B1 have been shown to down regulate proinflammatory cytokine levels including those of interferon (IFN)-γ, IFN-α, interleukin (IL)-1β, and IL-2 in broiler chickens. Fusarium mycotoxins exert part of their toxic effects by altering cytokine production in poultry. Mycotoxins adversely affect intestinal barrier functions by reducing the intestinal epithelial integrity and removing tight junction proteins. Apoptosis, increased colonisation of pathogenic microorganisms, cytotoxicity and oxidative stress, inhibition of protein synthesis and lipid peroxidation are characteristic of the toxic effects of mycotoxins on intestinal epithelium. These directly or indirectly affect host immune responses. Such immunotoxic effects of mycotoxins render poultry susceptible to many infectious diseases. The avian immune system is sensitive to most mycotoxins. Both cell-mediated and humoral immunity may be adversely affected after feeding mycotoxins to poultry. The avian immune system may be more sensitive to naturally contaminated feedstuffs because of the presence of multiple mycotoxins and the complex interactions between them which can cause severe adverse effects. Adverse effects of mycotoxins on the immune system reduce production and performance resulting in economic losses to poultry industries. Caution must be exercised while feeding grains contaminated with mycotoxins.
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Zavadova, Eva, Jan Spacek, Michal Vocka, Bohuslav Konopasek, and Lubos Petruzelka. "Decreased cellular and humoral immunity in patients with breast cancer." Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 4. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.4.
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4 Background: A growing body of evidence over the past few years suggests that the presence of immune elements within the tumor or in the tumor stroma has prognostic and predictive value in breast cancer. Immunotherapy is successfully used in many types of cancer, and modulation of immune system became standard part of the cancer patients treatment Responses in breast cancer have been more recently reported. However it has yet to be determined whether predictable biomarkers of response can be identified. Therefore in recent years, research focused on a precise description of the status and function of the immune system.The purpose of the study was to monitor immune responses in patients with breast cancer, particularly the examination of cellular (CD4, CD8, B cells) as well as humoral immunity (IgG, IgG1, IgG2, IgG3, IgG4. It appears that a factor contributing to the immunosupression may be a transforming factor-beta (TGF-beta).It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors. Methods: 50 patients included in the research project were implemented routine cancer treatment. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. Anti-tumor cellular immunity (CD4, CD8, CD19) was measured by flow citometry, humoral immunity (IgG, IgG1, IgG2, IgG3, IgG4) was measured and TGF beta and VEGF production was monitored by ELISA. Results: In breast cancer patients mainly depression in cellular immunity was found. Immunglobuline plasma level was decreased as well (mainly IgG4 subtype). TGF beta as well as VEGF plasma level were increased. Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections).Those patient could benefit from immunomodulation. Conclusions: The state of anticancer immunity could contribute to the selection of targeted immune therapy in breast cancer patients and to help to find optimal combination of immunotherapy. This project was supported by governmental grant AZV CR 15-28188A.
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Nieman, David C., Arnoud J. Groen, Artyom Pugachev, Andrew J. Simonson, Kristine Polley, Karma James, Bassem F. El-Khodor, Saradhadevi Varadharaj, and Claudia Hernández-Armenta. "Proteomics-Based Detection of Immune Dysfunction in an Elite Adventure Athlete Trekking Across the Antarctica." Proteomes 8, no. 1 (March 3, 2020): 4. http://dx.doi.org/10.3390/proteomes8010004.
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Proteomics monitoring of an elite adventure athlete (age 33 years) was conducted over a 28-week period that culminated in the successful, solo, unassisted, and unsupported two month trek across the Antarctica (1500 km). Training distress was monitored weekly using a 19-item, validated training distress scale (TDS). Weekly dried blood spot (DBS) specimens were collected via fingerprick blood drops onto standard blood spot cards. DBS proteins were measured with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) in data-independent acquisition (DIA) mode, and 712 proteins were identified and quantified. The 28-week period was divided into time segments based on TDS scores, and a contrast analysis between weeks five and eight (low TDS) and between weeks 20 and 23 (high TDS, last month of Antarctica trek) showed that 31 proteins (n = 20 immune related) were upregulated and 35 (n = 17 immune related) were downregulated. Protein–protein interaction (PPI) networks supported a dichotomous immune response. Gene ontology (GO) biological process terms for the upregulated immune proteins showed an increase in regulation of the immune system process, especially inflammation, complement activation, and leukocyte mediated immunity. At the same time, GO terms for the downregulated immune-related proteins indicated a decrease in several aspects of the overall immune system process including neutrophil degranulation and the antimicrobial humoral response. These proteomics data support a dysfunctional immune response in an elite adventure athlete during a sustained period of mental and physical distress while trekking solo across the Antarctica.
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Reap, Elizabeth A., Sergey A. Dryga, John Morris, Bryan Rivers, Pamela K. Norberg, Robert A. Olmsted, and Jeffrey D. Chulay. "Cellular and Humoral Immune Responses to Alphavirus Replicon Vaccines Expressing Cytomegalovirus pp65, IE1, and gB Proteins." Clinical and Vaccine Immunology 14, no. 6 (April 18, 2007): 748–55. http://dx.doi.org/10.1128/cvi.00037-07.
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ABSTRACT Development of vaccines against cytomegalovirus (CMV) is an important public health priority. We used a propagation-defective, single-cycle RNA replicon vector system derived from an attenuated strain of an alphavirus, Venezuelan equine encephalitis virus, to produce virus-like replicon particles (VRP) expressing various combinations of pp65, IE1, or gB proteins of human CMV. Protein expression in VRP-infected cells was highest with single-promoter replicons expressing pp65, IE1, a pp65/IE1 fusion protein, or the extracellular domain of gB and with double-promoter replicons expressing pp65 and IE1. Protein expression was lower with double- and triple-promoter replicons expressing gB, especially the full-length form of gB. BALB/c mice immunized with VRP expressing gB developed high titers of neutralizing antibody to CMV, and mice immunized with VRP expressing pp65, IE1, or a pp65/IE1 fusion protein developed robust antigen-specific T-cell responses as measured by gamma interferon enzyme-linked immunospot assay. Three overlapping immunodominant pp65 peptides contained a nine-amino-acid sequence (LGPISGHVL) that matches the consensus binding motif for a major histocompatibility complex H2-Dd T-cell epitope. These data provide the basis for further development and clinical evaluation of an alphavirus replicon vaccine for CMV expressing the pp65, IE1, and gB proteins.
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Xu, Shaohai, Shengmin Xu, Shaopeng Chen, Huadong Fan, Xun Luo, Xiaoyao Yang, Jun Wang, Hang Yuan, An Xu, and Lijun Wu. "Graphene Oxide Modulates B Cell Surface Phenotype and Impairs Immunoglobulin Secretion in Plasma Cell." Journal of Nanoscience and Nanotechnology 16, no. 4 (April 1, 2016): 4205–15. http://dx.doi.org/10.1166/jnn.2016.11712.
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Since discovery, graphene oxide (GO) has been used in all aspects of human life and revealed promising applications in biomedicine. Nevertheless, the potential risks of GO were always being revealed. Although GO was found to induce immune cell death and innate immune response, little is known regarding its toxicity to the specific adaptive immune system that is crucial for protecting against exotic invasion. The B-cell mediated adaptive immune system, which composed of highly specialized cells (B and plasma cell) and specific immune response (antibody response) is the focus in our present study. Using diverse standard immunological techniques, we found that GO modulated B cell surface phenotype, both costimulatory molecules (CD80, CD86 and especially CD40) and antigen presenting molecules (both classical and nonclassical) under the condition without causing cell death. Meanwhile, the terminal differentiated immunoglobulin (Ig) secreting plasma cell was affected by GO, which displayed a less secretion of Ig and more severe ER stress caused by the retention of the secreted form of Ig in cell compartment. The combined data reveal that GO has a particular adverse effect to B cell and the humoral immunity, directly demonstrating the potential risk of GO to the specific adaptive immunity.
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Sunyer, J. O., E. Gómez, L. Tort, V. Navarro, and J. Quesada. "Physiological responses and depression of humoral components of the immune system in gilthead sea bream (Sparus aurata) following daily acute stress." Canadian Journal of Fisheries and Aquatic Sciences 52, no. 11 (November 1, 1995): 2339–46. http://dx.doi.org/10.1139/f95-826.
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Changes in the immune system indicators serum hemagglutinating activity, complement levels, antibody titer, and lymphocyte number and in the plasma levels of cortisol and glucose in the gilthead sea bream (Sparus aurata) indicated that stress was induced when fish were chased daily for 8 min with a hand-held net for 16 days. Plasma levels of cortisol and glucose were elevated after 1 day and cortisol remained above prestress levels throughout the experiment. The immune system was altered as indicated by lymphocytopenia and decreases in hemolytic activity, agglutination capacity, and antibody titer. As these results show, for the first time, that the complement system is depressed after stress, a routine complement analysis is suggested as an additional technique for assessing the health status of fish.
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Hartl, Dominik, Rabindra Tirouvanziam, Julie Laval, Catherine M. Greene, David Habiel, Lokesh Sharma, Ali Önder Yildirim, Charles S. Dela Cruz, and Cory M. Hogaboam. "Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine." Journal of Innate Immunity 10, no. 5-6 (2018): 487–501. http://dx.doi.org/10.1159/000487057.
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The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.
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Michael, J. Dochniak. "Maladaptive Immunity and Metastasizing Cancer." Cancer Medicine Journal 3, no. 1 (June 30, 2020): 31–34. http://dx.doi.org/10.46619/cmj.2020.3-1017.
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The ability of innate immunity to inhibit metastatic cells is limited, based on Stage IV cancer survival rates. The dysregulation of the immune system through acquired immunity may result in pathological conditions that alter metastatic cells. Immunoglobulin-E (IgE) antibodies developed by the humoral immune system are a significant contributor to maladaptive immunity. Hypersensitivities are maladaptive immune reactions against harmless allergens. Forced allergen-specific immune responses may provide immediate-type allergies that affect the incidence and prevalence of endogenous proteins essential for metastasizing cells. Furthermore, allergies may shift the body’s resource allocation away from metastasizing cells to IgE-primed effector-cell proliferation. Therefore, research efforts need to explore if hyper-allergenic skin creams can be used to starve-out metastatic cells, wherever they are in the body, to determine if maladaptive immunotherapy is a viable treatment for Stage IV cancer.