Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Aglutininas/imunologia , Anticorpos Antivirais/sangue , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , Teste Sorológico para COVID-19 , Reações Cruzadas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The separation of plasma from whole blood is the first step in many diagnostic tests. Point-of-care tests often rely on integrated plasma filters, but protein retention in such filters limits their performance. Here, we investigate plasma separation on interlocked micropillar scaffolds ("synthetic paper") by the local agglutination of blood cells coupled with the capillary separation of the plasma. We separated clinically relevant volumes of plasma with high efficiency in a separation time on par with that of state of the art techniques. We investigated different covalent and noncovalent surface treatments (PEGMA, HEMA, BSA, O2 plasma) on our blood filter and their effect on protein recovery and identified O2 plasma treatment and 7.9 µg/cm2 agglutination antibody as most suitable treatments. Using these treatments, we recovered at least 82% of the blood plasma proteins, more than with state-of-the-art filters. The simplicity of our device and the performance of our approach could enable better point-of-care tests.
Assuntos
Proteínas Sanguíneas/isolamento & purificação , Filtração/métodos , Papel , Aglutininas/imunologia , Anticorpos/imunologia , Células Sanguíneas/citologia , Células Sanguíneas/metabolismo , Filtração/instrumentação , Humanos , Gases em Plasma/química , Sistemas Automatizados de Assistência Junto ao Leito , Propriedades de SuperfícieRESUMO
The aim of this study was to examine the direct reaction of specific lectin/agglutinin antibodies to different tissue antigens to confirm the theory that reactivity between them may contribute to autoimmunities. Lectins are carbohydrate-binding proteins found in nearly all fruits and vegetables. Undigested lectins can penetrate the gut barriers, provoking an immune response that results in the production of antibodies against them. Using an enzyme-linked immunosorbent assay, we reacted lectin-specific antibodies with 62 different tissue antigens. Wheat germ agglutinin-specific antibody was the most reactive with the tissue antigens (37 tissues out of 62), followed by red kidney bean phytohemagglutinin-specific antibody (20), soybean agglutinin-specific antibody (20), and peanut agglutinin-specific antibody (15). This reaction between anti-lectin antibodies and many human tissue antigens may be due to possible molecular mimicry and cross-reactivity. After our results confirmed that anti-lectin antibodies bind with human tissues, we wanted to determine the prevalence of these antibodies in the blood of 500 nominally healthy donors. The percentage elevation of antibodies against different lectins ranged from 12 to 16% (Immunoglobulin G), 9.7-14.7% (Immunoglobulin A), 12-18% (Immunoglobulin M), and 7.8-14.6% (Immunoglobulin E). Serial dilutions and inhibition study confirmed that these reactions were specific. Finally, we tested the lectin-specific antibody level in sera both negative and positive for RF and ANA and found that IgM anti-lectin antibody levels were highly correlated with RF but not with ANA level. The reaction of anti-lectin antibodies with human tissue components and their detection in RF-positive samples may describe mechanisms by which the production of antibodies against undigested lectins may contribute to the pathogenesis of some autoimmune diseases.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade , Lectinas/imunologia , Adolescente , Adulto , Idoso , Aglutininas/imunologia , Especificidade de Anticorpos/imunologia , Doenças Autoimunes/etiologia , Suscetibilidade a Doenças , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Adulto JovemRESUMO
BACKGROUND: Major ABO mismatch between donor and recipient in bone marrow transplantation (BMT) may cause hemolysis, delayed red blood cell (RBC) engraftment and pure red cell aplasia (PRCA), which result in increased transfusion needs. High pretransplant anti-A/B antibody titers have been associated with increased risk of PRCA. Herein, we studied the impact of anti-A/B titers on transfusion needs after BMT with major ABO mismatch. METHODS: We reviewed the medical charts of 27 patients who underwent to BMT with major ABO mismatch and categorized them into two groups according to anti-A/B titers of IgG (≤16 and ≥32). We recorded the number of RBC and platelet units transfused in the first 180 days after transplantation. We also evaluated the impact of anti-A/B titers on overall survival. RESULTS: Patients with anti-A/B titer ≥32 of IgG class required more RBC transfusion than patients with titer ≤16 (6.60±4.55 vs 21.29±14.68; P=.03). Anti-A/B of IgM class had no impact on both RBC and platelet transfusion needs. Anti-A/B titers had no impact on overall survival. CONCLUSION: Higher titers of anti-A/B antibodies of IgG class, but not of IgM, are associated with a higher demand for RBC transfusion.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Aglutininas/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Transplante de Medula Óssea/métodos , Transfusão de Eritrócitos/estatística & dados numéricos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemRESUMO
Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication. The design was based on the inclusion of the immunogenic region of the full length protein and the minimal essential folding domains required for inducing neutralizing antibody response. The chimera also contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Active immunization with the chimera protected all the mice challenged with 45 X LD50 of abrin. Also, passive transfer of antibodies raised against the chimera rescued all mice challenged with 50 X LD50 of toxin. Hence the chimeric protein appears to be a promising vaccine candidate against abrin induced lethality.
Assuntos
Abrina/toxicidade , Abrus/química , Aglutininas/imunologia , Lectinas de Plantas/imunologia , Intoxicação por Plantas/prevenção & controle , Proteínas Recombinantes de Fusão/imunologia , Abrina/genética , Abrus/imunologia , Abrus/intoxicação , Animais , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Epitopos , Feminino , Humanos , Células Jurkat , Camundongos Endogâmicos BALB C , Lectinas de Plantas/genética , Intoxicação por Plantas/imunologia , Conformação Proteica , Coelhos , Proteínas Recombinantes de Fusão/genética , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologiaRESUMO
Lectins are carbohydrate-binding proteins present throughout nature that act as agglutinins. Approximately 30% of our food contains lectins, some of which may be resistant enough to digestion to enter the circulation. Because of their binding properties, lectins can cause nutrient deficiencies, disrupt digestion, and cause severe intestinal damage when consumed in excess by an individual with dysfunctional enzymes. These effects are followed by disruption of intestinal barrier integrity, which is the gateway to various autoimmunities. Shared amino acid motifs between dietary lectins, exogenous peptides, and various body tissues may lead to cross-reactivity, resulting in the production of antibodies against lectin and bacterial antigens, followed by autoimmunity. The detection of immunoglobulin G (IgG) or immunoglobulin A (IgA) antibodies against specific lectins may serve as a guide for the elimination of these lectins from the diet. It is proposed that this process can reduce the peripheral antigenic stimulus and, thereby, result in a diminution of disease symptoms in some-but not all-patients with autoimmune disorders.
Assuntos
Aglutininas/imunologia , Doenças Autoimunes , Lectinas/imunologia , Citocinas , Humanos , Modelos ImunológicosRESUMO
After mucosal damage or gingival inflammation, complement proteins leak into the oral cavity and mix with salivary proteins such as salivary agglutinin (SAG/gp-340/DMBT1). This protein is encoded by the gene Deleted in Malignant Brain Tumors 1 (DMBT1), and it aggregates bacteria, viruses and fungi, and activates the lectin pathway of the complement system. In the lectin pathway, carbohydrate structures on pathogens or altered self cells are recognized. SAG is highly glycosylated, partly on the basis of the donor's blood group status. Whereas secretors express Lewis b, Lewis y, and antigens from the ABO-blood group system on SAG, non-secretors do not. Through mannose-binding lectin (MBL) binding and C4 deposition assays, we aimed to identify the chemical structures on SAG that are responsible for complement activation. The complement-activating properties of SAG were completely abolished by oxidation of its carbohydrate moiety. SAG-mediated activation of complement was also inhibited in the presence of saccharides such as fucose and Lewis b carbohydrates, and also after pretreatment with the fucose-binding lectin, Anguilla anguilla agglutinin. Complement activation was significantly (p<0.01) higher in secretors than in non-secretors. Our results suggest that fucose-rich oligosaccharide sidechains, such as Lewis b antigens, are involved in the activation of complement by SAG.
Assuntos
Aglutininas/imunologia , Ativação do Complemento/imunologia , Saliva/imunologia , Humanos , Imunidade Inata , Lectina de Ligação a Manose/imunologiaRESUMO
PURPOSE: The ABO gene locus is associated with the risk of developing pancreatic ductal adenocarcinoma (PDAC) resulting in an increased incidence in individuals with non-O blood groups. Up to 90% of PDAC specimens display alterations in mucin type O-GalNAc glycosylation. Because aberrant O-GalNAc glycans (Tn and T antigen) are structurally related to blood group A and B glycans, we investigated the role of IgM isoagglutinins in PDAC. EXPERIMENTAL DESIGN: Binding studies of IgM isoagglutinins toward blood group A, B, Tn antigen, and T antigen glycoconjugates from patients with PDAC and healthy individuals were conducted. Isoagglutinin titers and total IgM were compared between patients with PDAC and control group. An anti-A antibody was used for immunoprecipitation of aberrant O-glycosylated tumor proteins and subsequent mass spectromic analysis. RESULTS: We found that IgM isoagglutinins bind blood group antigens, Tn and T glycoconjugates as well as tumor-derived glycoproteins. Blood group A isoagglutinins exhibited a strong binding toward blood group B antigen and T antigen, whereas blood group B showed binding to blood group A antigen and Tn antigen. Furthermore, we confirmed a decreased frequency in individuals with blood group O and observed a significant decrease of IgM isoagglutinin titers in PDAC sera compared with control sera, whereas total IgM levels were unaltered. We identified new PDAC-derived O-GalNAc glycoproteins by mass spectrometry using a blood group A-specific antibody. CONCLUSION: Our data elucidated a novel interaction of blood group IgM isoagglutinins and PDAC O-GalNAc glycoproteins that may contribute to the pathogenesis and progression of pancreatic cancer.
Assuntos
Sistema ABO de Grupos Sanguíneos , Aglutininas/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Imunoglobulina M/metabolismo , Neoplasias Pancreáticas/metabolismo , Polissacarídeos/metabolismo , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Idoso , Aglutininas/sangue , Aglutininas/imunologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Ligação Proteica , Adulto JovemRESUMO
The murine and the human genome have global properties in common. So the murine anti-A-specific complementary IgM and related human innate isoagglutinin represent developmental, 2-mercaptoethanol-sensitive, complement-binding glycoproteins, which do not arise from any measurable environmentally-induced or auto- immune response. The murine anti-A certainly originates from a cell surface- or cell adhesion molecule, which in the course of germ cell development becomes devoid of O-GalNAc-transferase and is released into the circulation. In human sera the enzyme occurs exclusively in those of blood group A- and AB subjects, while in group O(H) an identically encoded protein lets expect an opposite function and appears in conjunction with a complementary anti-A reactive glycoprotein. Since O-glycosylations rule the carbohydrate metabolism in growth and reproduction processes, we propose that the ancestral histo-(blood)-group A molecule arises in the course of O-GalNAc-glycosylations of glycolipids and protein envelops at progenitor cell surfaces. Germ cell development postulates embryonic stem cell fidelity, which is characterised by persistent production of α-linked O-GalNAc-glycans. They are determined by the A-allele within the human, "complete" histo (blood) group AB(O) structure that in early ontogeny is hypothesised to be synthesised independently from the final phenotype. The structure either passes "completely" through the germline, in transferase-secreting mature tissues becoming the "complete" phenotype AB, or disappears in exhaustive glycotransferase depletion from the differentiating cell surfaces and leaves behind the "incomplete" blood group O-phenotype, which has released a transferase- and O-glycan-depleted, complementary glycoprotein (IgM) into the circulation. The process implies, that in humans the different blood phenotypes evolve from a "complete" AB(O) molecular complex in a distinct enzymatic and/or complement cascade suggesting O-glycanase involvements. While the murine and human oocyte zona pellucida express identical O-glycans, the human phenotype O might be explainable by the kinetics of the murine ovarian O-GalNAc glycan synthesis and the complementary anti-A released in parallel. The maturing murine ovary may provide insight into encoding of the physiologically superior α-linked GalNAc ancestral epitope that becomes essential in reproduction as well as in tissue renewal events. According to recent reports, O-GalNAc-transferase-determined blood group A suggests superiority in human female fertility and was called even "protective". So the minor fertility of blood-group-O females may reside in a critical timing in developmental shifting of enzyme functions affecting the formation of GalNAc-determined hormone receptors on the way to maturation. Experiments that had inserted an oocyte genome into a somatic one to generate pluripotent stem cells, might elucidate a developmental dilemma by testing oocytes from different blood group AB donors donors. Perhaps they will unmask the molecular basis of an evolutionary trend, while stem cell generation itself capitalises on the enzymatically-advantaged, lineage-maintaining (histo) blood group A-allele, which guaranties ancestral functional completeness.
Assuntos
Imunidade Inata , Imunoglobulina M/biossíntese , N-Acetilgalactosaminiltransferases/metabolismo , Aglutininas/imunologia , Animais , Antígenos/imunologia , Evolução Biológica , Humanos , Camundongos , N-Acetilgalactosaminiltransferases/genética , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
Genetic engineering has established itself to be an important tool for crop improvement. Despite the success, there is always a risk of food allergy induced by alien gene products. The present study assessed the biosafety of mutant Allium sativum leaf agglutinin (mASAL), a potent antifungal protein generated by site directed mutagenesis of Allium sativum leaf agglutinin (ASAL). mASAL was cloned in pET28a+ and expressed in E. coli, and the safety assessment was carried out according to the FAO/WHO guideline (2001). Bioinformatics analysis, pepsin digestion, and thermal stability assay showed the protein to be nonallergenic. Targeted sera screening revealed no significant IgE affinity of mASAL. Furthermore, mASAL sensitized Balb/c mice showed normal histopathology of lung and gut tissue. All results indicated the least possibility of mASAL being an allergen. Thus, mASAL appears to be a promising antifungal candidate protein suitable for agronomical biotechnology.
Assuntos
Aglutininas/genética , Aglutininas/imunologia , Antifúngicos/imunologia , Alho/imunologia , Aglutininas/química , Animais , Antifúngicos/química , Feminino , Alho/química , Alho/genética , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Folhas de Planta/química , Folhas de Planta/genética , Folhas de Planta/imunologia , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estabilidade ProteicaRESUMO
The ribonuclease (RNase) A superfamily lineage includes distant members with antimicrobial properties, suggesting a common ancestral host-defense role. In an effort to identify the minimal requirements for the eosinophil cationic protein (ECP or RNase 3) antimicrobial properties we applied site-directed mutagenesis on its closest family homolog, the eosinophil-derived neurotoxin (EDN or RNase 2). Both eosinophil secretion proteins are involved in human immune defense, and are reported as being among the most rapidly evolving coding sequences in primates. Previous studies in our laboratory defined two regions at the N-terminus involved in the protein antimicrobial action, encompassing residues 8-16 and 34-36. Here, we demonstrate that switching two single residues is enough to provide EDN with ECP antipathogen properties. That is, the EDN double-mutant Q34R/R35W displays enhanced bactericidal activity, particularly towards Gram-negative bacteria, and a significant increase in its affinity towards the bacterial outer membrane lipopolysaccharides. Moreover, we confirmed the direct contribution of residue W35 in lipopolysaccharide binding, membrane interaction and permeabilization processes. Furthermore, additional T13 to I substitution provides EDN with an exposed hydrophobic patch required for protein self-aggregation and triggers bacterial agglutination, thereby increasing the final antimicrobial activity by up to 20-fold. Our results highlight how single selected mutations can reshape the entire protein function. This study provides an example of how structure-guided protein engineering can successfully reproduce an evolution selection process towards the emergence of new physiological roles.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/imunologia , Engenharia de Proteínas/métodos , Ribonuclease Pancreático/genética , Ribonuclease Pancreático/imunologia , Aglutininas/genética , Aglutininas/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/química , Endorribonucleases/química , Endorribonucleases/genética , Endorribonucleases/imunologia , Proteína Catiônica de Eosinófilo/química , Proteína Catiônica de Eosinófilo/genética , Proteína Catiônica de Eosinófilo/imunologia , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Mutação Puntual , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Ribonuclease Pancreático/químicaAssuntos
Alérgenos/imunologia , Hipersensibilidade Imediata/diagnóstico , Imunoglobulina E/sangue , Venenos de Vespas/imunologia , Aglutininas/química , Aglutininas/imunologia , Alérgenos/química , Animais , Reações Cruzadas , Humanos , Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/imunologia , Imunoensaio , Sensibilidade e Especificidade , VespasRESUMO
Reliability of the Widal tube agglutination test has been the subject of many controversies over the years. This study was performed to assess the effect of certain modifications on the performance of Widal test in a novel microplate assay. Sera from 37 patients (21 males; 16 females) (mean age 28 +/- 7 years) were tested in the Immunology Unit at King Khalid University Hospital, Riyadh. Among them were 26 patients with suspected typhoid fever and 11 had bacteriologically confirmed diagnosis of Salmonella infection. The modifications included either the use of 0.5% bovine serum albumin (BSA), absorption of sera with sheep red blood cells (SRBC) or heat inactivation of sera. Compared with Widal tube agglutination test, microplate assay with SRBC absorption of the sera from patients with suspected typhoid fever was not only associated with enhancement of detection titers for both H (p < or = 0.001) and O (p < or = 0.005) Salmonella agglutinins but also the percentage of reactivity. The presence of BSA augmented detection titers for Salmonella H agglutinins (p < or = 0.02) only. Heat inactivation of sera however was found to be associated with reduction in the detectable titers for both H (p < or = 0.03) and O (p < or = 0.01) agglutinins. Increased titers of Salmonella agglutinins were also evident in 11 patients with confirmed diagnosis of Salmonella infection. The novel microplate agglutination assay using the SRBC absorption was associated with enhancement in Widal test reactivity and appears to be a useful alternative for the diagnosis of Salmonella infection.
Assuntos
Testes de Aglutinação/métodos , Febre Tifoide/diagnóstico , Adulto , Testes de Aglutinação/instrumentação , Aglutininas/análise , Aglutininas/imunologia , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/análise , Proteínas de Bactérias/imunologia , Feminino , Humanos , Masculino , Salmonella typhi/imunologia , Salmonella typhi/isolamento & purificação , Febre Tifoide/microbiologia , Adulto JovemRESUMO
Although many insect resistance genes have been identified, the number of studies examining their effects in combination using transgenic systems is limited. This study introduced a construct into maize containing the coding sequence for maize ribosome-inactivating protein (MRIP) and wheat germ agglutinin (WGA). Many transformants produced both the MRIP and WGA in leaves. Mature leaves expressing higher levels of these two proteins were more resistant to feeding by first-instar larvae of fall armyworms (Spodoptera frugiperda) and corn earworms (Helicoverpa zea), and the level of resistance was correlated with levels of MRIP and WGA. There was also some indication that resistance to Fusarium verticillioides was increased in the transgenic plant leaves. No statistically significant synergism or antagonism occurred between the activities of the two proteins. MRIP and WGA represent compatible class examples of food plant-derived proteins for multigene resistance to insects.
Assuntos
Aglutininas/imunologia , Mariposas/fisiologia , Controle Biológico de Vetores/métodos , Doenças das Plantas/parasitologia , Proteínas de Plantas/imunologia , Plantas Geneticamente Modificadas/imunologia , Zea mays/imunologia , Aglutininas/genética , Animais , Resistência à Doença , Mariposas/imunologia , Doenças das Plantas/imunologia , Folhas de Planta/genética , Folhas de Planta/imunologia , Folhas de Planta/parasitologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/parasitologia , Proteínas Inativadoras de Ribossomos/genética , Proteínas Inativadoras de Ribossomos/imunologia , Triticum/genética , Regulação para Cima , Zea mays/genética , Zea mays/parasitologiaRESUMO
BACKGROUND: Oxaliplatin is one of the platinum chemotherapeutics that includes cisplatin and carboplatin. Antibodies to all three drugs have caused immune hemolytic anemia (IHA). In an investigation of oxaliplatin-induced IHA, the negative plasma control agglutinated oxaliplatin-coated red blood cells (RBCs). Previous preparations of this control had not agglutinated oxaliplatin- or cisplatin-coated RBCs. STUDY DESIGN AND METHODS: Drug-coated RBCs, prepared by incubating 1/10th volume of RBCs with 1 mg/mL drug in phosphate-buffered saline for 1 hour at 37°C, were incubated with plasma from random blood donors and patients. Plasma was treated with dithiothreitol to determine the immunoglobulin class. Hapten inhibition was performed by incubating plasma with solutions of oxaliplatin or cisplatin. RESULTS: Nineteen of 121 (16%) donors' plasma samples agglutinated oxaliplatin-coated RBCs; 7 of 102 (7%) donors' plasma samples agglutinated cisplatin-coated RBCs. Two of 50 (4%) patients' samples agglutinated oxaliplatin-coated RBCs. The agglutinin was immunoglobulin M and inhibited by oxaliplatin and cisplatin. CONCLUSION: An agglutinin reactive with oxaliplatin-coated RBCs was found in 16% of donors' and 4% of patients' samples. Inhibition by oxaliplatin and cisplatin indicates the antibody may be directed to platinum. The presence of this antibody in healthy individuals may be related to the increasing environmental presence of platinum in air and soil as a byproduct of automobile catalytic converters and pharmaceuticals in our water and food chain. This antibody in individuals without IHA suggests that testing untreated and enzyme-treated RBCs in the presence of a solution of drug may be the best method to investigate IHA caused by drugs in the platinum family.
Assuntos
Anticorpos/sangue , Doadores de Sangue , Compostos Organoplatínicos/imunologia , Plasma/imunologia , Testes de Aglutinação , Aglutininas/imunologia , Aglutininas/metabolismo , Antineoplásicos/imunologia , Testes de Coagulação Sanguínea , Portadores de Fármacos , Eritrócitos/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Saúde , Humanos , Oxaliplatina , Plasma/metabolismoRESUMO
Immunological parameters in different periods of acute radiation syndrome (ARS) of experimental animals and Chernobyl reactor accident-injured patients have been studied. 148 patients and experimental animals (123 dogs and 198 monkeys) were observed after radiation exposure of different levels (from a sub-lethal dose to the minimal absolute lethal dose). We have found the increase in the C-reactive protein, fluctuation of normal antibody titers and the complement in blood serum, as well as the growing number of skin microbes after exposures to lethal doses. Experimental results match clinical data in terms of ARS progress phases but differ from the latter in terms of the time of clinical manifestations. The highest rate of clinical manifestations is observed on the 7-14 days for experimental animals (rats, dogs and monkeys) and on the 20-30 days for patients after radiation exposure. Regenerative processes in animals run faster than those in humans.
Assuntos
Síndrome Aguda da Radiação/imunologia , Adaptação Fisiológica/efeitos da radiação , Acidente Nuclear de Chernobyl , Lesões Experimentais por Radiação/imunologia , Síndrome Aguda da Radiação/sangue , Síndrome Aguda da Radiação/etiologia , Aglutininas/sangue , Aglutininas/imunologia , Animais , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , Contagem de Colônia Microbiana , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Cães , Relação Dose-Resposta Imunológica , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Humanos , Macaca mulatta , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/etiologia , Índice de Gravidade de Doença , Pele/imunologia , Pele/microbiologia , Pele/efeitos da radiação , Especificidade da Espécie , Staphylococcus/isolamento & purificação , Fatores de TempoRESUMO
Aberrancies in IgA1 glycosylation have been linked to the pathogenesis of IgA nephropathy (IgAN), a kidney disease characterized by deposits of IgA1-containing immune complexes in the glomerular mesangium. IgA1 from IgAN patients is characterized by the presence of galactose (Gal)-deficient O-glycans in the hinge region that can act as epitopes for anti-glycan IgG or IgA1 antibodies. The resulting circulating immune complexes are trapped in the glomerular mesangium of the kidney where they trigger localized inflammatory responses by activating mesangial cells. Certain lectins recognize the terminal N-acetylgalactosamine (GalNAc)-containing O-glycans on Gal-deficient IgA1 and can be potentially used as diagnostic tools. To improve our understanding of GalNAc recognition by these lectins, we have conducted binding studies to assess the interaction of Helix aspersa agglutinin (HAA) and Helix pomatia agglutinin (HPA) with Gal-deficient IgA1. Surface plasmon resonance spectroscopy revealed that both HAA and HPA bind to a Gal-deficient synthetic hinge region glycopeptide (HR-GalNAc) as well as various aberrantly glycosylated IgA1 myeloma proteins. Despite having six binding sites, both HAA and HPA bind IgA1 in a functionally bivalent manner, with the apparent affinity for IgA1 related to the number of exposed GalNAc groups in the IgA1 hinge. Finally, HAA and HPA were shown to discriminate very effectively between the IgA1 secreted by cell lines derived from peripheral blood cells of patients with IgAN and that from cells of healthy controls. These studies provide insight into lectin recognition of the Gal-deficient IgA1 hinge region and lay the groundwork for the development of reliable diagnostic tools for IgAN.
Assuntos
Acetilgalactosamina/imunologia , Galactose/imunologia , Imunoglobulina A , Lectinas/metabolismo , Polissacarídeos/química , Polissacarídeos/imunologia , Acetilgalactosamina/metabolismo , Aglutininas/imunologia , Aglutininas/metabolismo , Animais , Anticorpos Anti-Idiotípicos , Complexo Antígeno-Anticorpo/imunologia , Complexo Antígeno-Anticorpo/metabolismo , Sítios de Ligação/imunologia , Epitopos/imunologia , Epitopos/metabolismo , Galactose/metabolismo , Mesângio Glomerular/imunologia , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Glicosilação , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Rim/imunologia , Rim/metabolismo , Rim/patologia , Lectinas/imunologia , Proteínas do Mieloma/imunologia , Proteínas do Mieloma/metabolismo , Polissacarídeos/metabolismo , Caramujos/imunologia , Caramujos/metabolismoRESUMO
BACKGROUND: Antigen exposure is one of the major exogenous factors modulating human immunocompetence acquisition. Decline in family size and improvements in public health and hygiene in developed countries, may deprive the immune system of appropriate antigen input by diminishing infectious stimuli. Probiotics are a large group of microorganisms defined by their beneficial effects on human health and with stimulating effects on different functions of the immune system. AIM OF THE STUDY: We conducted a double-blind, placebo-controlled trial to determine if probiotics maintain their immune-stimulating effects in a population of 162 children with a high index of natural exposure to microorganisms. Children were to ingest for at least 4 months one of two products, low-fat milk fermented by Streptococcus thermophilus (control product) or low-fat milk fermented by S. thermophilus and Lactobacillus casei, with Lactobacillus acidophilus, oligofructose and inulin added after the fermentation process (test product). According to their age, children were vaccinated with DTP-Hib vaccine or a 23-valent anti-pneumococcal vaccine. RESULTS: Final analysis of results was done in 70 children in each group, showing that the rate of immunoglobulin and isoagglutinin acquisition was similar in both groups. There was no difference between groups in antibody levels neither before nor after vaccination. Days of fever and number of episodes of infection were not statistically different in either group. CONCLUSIONS: Supplementation of standard fermented milk with additional probiotics was not of benefit. The high natural rate of early microbial exposure in infants and children from a population of low socio-economic status living in a "less hygienic environment" may account for the absence of an additional immune-stimulating effect by supplementary probiotics.