T cell immune responses deciphered.

A machine-learning approach reveals antigen encoding that predicts T cell responses.

Atopic Dermatitis: Identification and Management of Complicating Factors.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, associated with impaired skin barrier function and an atopic background. Various complicating factors, such as irritants, aeroallergens, food, microbial organisms, contact allergens, sweat, and scratching can induce the development of AD symptoms. Irritants, including soap/shampoo and clothes, can cause itching and eczematous lesions. In addition, young children with AD tend to become sensitized to eggs, milk, or peanuts, while older children and adults more often become sensitized to environmental allergens, such as house dust mites (HDM), animal dander, or pollen. Serum-specific IgE levels and skin prick test reactions to food tend to show high negative predictive values and low specificity and positive predictive values for diagnosing food allergy. On the other hand, AD adult patients tend to have severe skin symptoms and exhibit high HDM-specific IgE levels. Microbial organisms, e.g., Staphylococcus aureus and Malassezia furfur, might contribute to the pathogenetic mechanisms of AD. While sweat plays a major role in maintaining skin homeostasis, it can become an aggravating factor in patients with AD. Furthermore, scratching often exacerbates eczematous lesions. Several patient-specific complicating factors are seen in most cases. The identification and management of complicating factors are important for controlling AD.

Prevalencia del antígeno D débil y su clasificación fenotípica en donantes voluntarios de sangre / Prevalence of "weak" D antigen and its phenotypic classification in voluntary blood donours / Prevalência do antígeno D "fraco" e sua classificação fenotípica em doadores voluntários de sangue

En el campo de la medicina transfusional la correcta identificación de los fenotipos del sistema Rh y en especial del antígeno D debe ser de manera inequívoca por su relevancia clínica. El antígeno D tiene variantes denominadas D parcial, D débil y DEL, las que se producen por mutaciones de los alelos RHD/RHCE o por una supresión en la expresión fenotípica. Se trató de un estudio descriptivo, retrospectivo de corte transversal en el que se realizó una revisión de registros primarios durante el período 2011-2014 validados de acuerdo con el protocolo de Hernández-Sampieri R. Se utilizó estadística descriptiva mediante la aplicación del software informático SPSS versión 22.0 y se estableció la relación entre variables independientes a través del análisis estadístico de Chi-cuadrado. Se determinó una prevalencia de donantes RhD negativos de 1,8 a 2,5% y RhD débil de 1,79 a 2,28%. La fenotipificación serológica permitió identificar que los tipos 2 y 5 eran los más frecuentes. También se estableció la existencia de aloinmunización por anti-D, anti-C y anti-E. Se estableció de esta manera la existencia de D débil y una importante aloinmunización en la población de donantes de sangre tipificados como D negativo y D débil, por lo que se recomienda implementar un algoritmo de identificación del antígeno D en servicios de medicina transfusional.

In the field of transfusion medicine, the correct identification of the phenotypes of the Rh system and especially of the D antigen must be unequivocal for clinical relevance. The D antigen has variants called partial D, weak D and DEL. These are produced by mutations of the RHD/RHCE alleles or a suppression in phenotypic expression. The objective of this study was to establish the frequency of weak D antigen in the population of blood donours from 17 Ecuadorian states and their phenotypic combinations. It was a descriptive, retrospective cross-sectional study performed during the 2011-2014 period and validated with primary records in accordance with the Hernández-Sampieri R protocol. A descriptive statistics through the application of SPSS computer software version 22.0 was used and the relationship between independent variables through the Chi-square statistic method was established. A prevalence of RhD negative donours from 1.8 to 2.5% and weak D 1.79 to 2.28% was observed The serological phenotyping made it possible to identify that type 2 and 5 were the most frequent. The presence of alloimmunization by anti-D, anti-C and anti-E was also established. Besides, the presence of weak D types and significant alloimmunization in the donour population of blood typed as D negative and weak was established, so it is recommended to implement an algorithm for the identification of D antigen in transfusional medicine services.

No campo da medicina transfusional, a correta identificação dos fenótipos do sistema Rh e especialmente do antígeno D deve ser inequívoca devido a sua relevância clínica. O antígeno D tem variantes chamadas de D parcial, D fraca e DEL, as quais são produzidos por mutações dos alelos RHD/RHCE ou por uma supressão na expressão fenotípica. O objetivo deste estudo foi estabelecer a frequência do antígeno D fraco em uma população de doadores de sangue de 17 províncias equatorianas e suas combinações fenotípicas. Foi uma estudo descritivo, retrospectivo de corte transversal em que se realizou uma revisão dos registros primários validados de acordo com o Protocolo Hernández-Sampieri R durante o período 2011-2014. Utilizou-se estatísticas descritivas através da aplicação do software informático SPSS versão 22.0 e a relação entre variáveis independentes através da análise estatística de qui-quadrado. Foi determinada uma prevalência de doadores RhD negativos de 1,8 a 2,5% e RhD fraco de 1,79 a 2,28%. A genotipagem serológica permitiu identificar que os tipos 2 e 5 são os mais frequente. A existência de alo imunização por anti-D, anti-C e anti-E também foi estabelecida. A existência de D fraco e uma alo imunização significativa na população de doadores de sangue tipificados como D negativo e fraco, por isso é recomendado implementar um algoritmo de identificação do antígeno D em serviços de medicina transfusional.

Hypersensitivity pneumonitis: Antigen diversity and disease implications.

Hypersensitivity pneumonitis (HP) is an immune-mediated syndrome triggered by inhalation of a wide variety of allergens, to which an individual has previously been sensitized. More than 200 agents responsible for the disease have already been identified; however, HP occurs only in a small number of individuals exposed to causal antigens. The present report provides an overview of the role of antigen role in HP, highlighting its diversity, research methods, and prevention strategies, as well as the impact on disease prognosis following elimination of antigen. HP is an underdiagnosed disease and, therefore, it is difficult to accurately estimate its incidence. Triggering antigens can be divided into six broad categories: bacteria, fungi, mycobacteria, animal and plant proteins, chemicals, and metals, represented by disease prototypes. The identification of causal antigen is a major challenge; it is impossible to obtain in about 30-60% of cases. The acute form of HP, with early detection and immediate eviction of causal antigen, tends to have an excellent prognosis. In the chronic form, partial recovery of disease is still possible; however, some cases tend to progress to fibrosis, even after removal from exposure. In conclusion, HP diagnosis should be based on a proactive search for potential antigen sources, although their identification is hampered by the lack of standardized methods of demonstrating the specific antigen sensitization. Antigen avoidance is a critical determinant in disease prognosis.

Development of RBC Membrane Antigen Arrays for Validating Blood Grouping Reagents.

Antibody reagents have been remained as a standard approach to characterize blood group (BG) antigens in clinic. The specificity and cross-reactivity of these BG antibodies are routine detected using the gel microcolumn assay (GMA). However, the GMA is neither specific nor sensitive, thus increasing the risk of improperly matched RBC transfusions. In this work, we describe a bead-based RBC membrane antigen array to detect BG antibody-antigen binding with ∼700-fold higher sensitivity and dynamic range than the GMA. RBC membrane antigen arrays were fabricated using fragmented RBC membranes highly enriched in BG panel antigens. The arrays were then used to screen the interactions of 15 BG reagents to three antigen panels. The majority of the antibody reactions (i.e., 86.7%; 39/45) aligned with those obtained with the GMA. The six cross-reactive, nonspecific antibody reactions identified only by our arrays (i.e., 13.3%; 6/45) were confirmed by agglutination inhibition and genotyping assays. These results demonstrate that our RBC membrane antigen array has great potential in screening BG antibodies and improving the safety of RBC transfusions.

dbDiarrhea: the database of pathogen proteins and vaccine antigens from diarrheal pathogens.

Diarrhea occurs world-wide and is most commonly caused by gastrointestinal infections which kill around 2.2 million people globally each year, mostly children in developing countries. We describe here dbDiarrhea, which is currently the most comprehensive catalog of proteins implicated in the pathogenesis of diarrhea caused by major bacterial, viral and parasitic species. The current release of the database houses 820 proteins gleaned through an extensive and critical survey of research articles from PubMed. The major contributors to this compendium of proteins are Escherichia coli and Salmonella enterica. These proteins are classified into different categories such as Type III secretion system effectors, Type III secretion system components, and Pathogen proteins. There is another complementary module called 'Host proteins'. dbDiarrhea also serves as a repository of the research articles describing (1) trials of subunit and whole organism vaccines (2) high-throughput screening of Type III secretion system inhibitors and (3) diagnostic assays, for various diarrheal pathogens. The database is web accessible through an intuitive user interface that allows querying proteins and research articles for different organism, keywords and accession number. Besides providing the search facility through browsing, the database supports sequence similarity search with the BLAST tool. With the rapidly burgeoning global burden of the diarrhea, we anticipate that this database would serve as a source of useful information for furthering research on diarrhea. The database can be freely accessed at http://www.juit.ac.in/attachments/dbdiarrhea/diarrhea_home.html.

Synthesis and NMR studies on the ABO histo-blood group antigens: synthesis of type III and IV structures and NMR characterization of type I-VI antigens.

The ABO histo-blood group antigens are best known for their important roles in solid organ and bone marrow transplantation as well as transfusion medicine. Here we report the synthesis of the ABO type III and IV antigens with a 7-octen-1-yl aglycone. Also described is an NMR study of the ABO type I to VI antigens, which were carried out to probe differences in overall conformation of the molecules. These NMR investigations showed very little difference in the (1)H chemical shifts, as well as (1)H-(1)H coupling constants, across all compounds, suggesting that these ABO subtypes adopt nearly identical conformations in solution.

Inmunonutrición: primera parte / Immunonutrition: first part

El campo de la inmunonutrición es relativamente nuevo y está siendo estudiado a nivel mundial por su gran aplicabilidad en la medicina. Se denomina resistencia específica o inmunidad a la capacidad del cuerpo humano para defenderse contra agentes invasores específicos, como bacterias, toxinas, virus y tejidos extraños; y se define estrés oxidativo como una situación en la que existe tanto un aumento en la velocidad de generación de especies reactivas del oxígeno como una disminución de los sistemas de defensa del organismo. La desnutrición calórica y proteica, que incluye también, invariablemente, la privación de vitaminas y minerales, puede causar una desnutrición primaria relacionada con la atrofia de órganos linfoides, lo cual conduce al desarrollo de infecciones oportunistas. Para poder entender el efecto de los farmaconutrimentos en el tubo digestivo y en el sistema inmunitario, hay que entender las bases fisiológicas de la inmunonutrición, lo cual requiere la integración de procesos de regulación a nivel del intestino.

The field of immunonutrition is relatively new and is being studied worldwide for its wide applicability in medicine. It is called the specific resistance or immunity to the human body's ability to defend against specific inaders such as bacteria, toxins, viruses and foreign tissue, and oxidative stress is defined as a situation in which there is both an increase in the rate of generation of reactive oxygen species as a decrease in the body's defense systems. Caloric and protein malnutrition, which also includes invariably deprived of vitamins and minerals can cause malnutritionrelated primary lymphoid organ atrophy, leading to the development of opportunistic infections. To understand the effect of pharmacology and nutrients in the digestive tract and immune system, one must understand the physiological basis of immunonutrition, which requires the integration of regularoty processes in the intestine.

Molecular systematics of the neotropical scorpion genus Tityus (Buthidae): the historical biogeography and venom antigenic diversity of toxic Venezuelan species.

We provide a mitochondrial DNA-based phylogenetic hypothesis for 21 Tityus species collected in Venezuela, Trinidad, Brazil and Panama, including 12 taxa known to be toxic to humans. Our phylogenetic reconstruction is based on 850 nucleotides of the combined cytochrome oxidase subunit I and 16S rRNA genes for most species, and centered on Venezuelan scorpions owing to the detailed taxonomic and biogeographic information available for Tityus in this region. The principal phylogenetic result was the strong support for mtDNA clades representing geographical groupings associated with the Perijá mountain range, the Mérida Andes, or the central and eastern coastal ranges in Venezuela, suggesting that vicariance has been a potent force in the diversification of local scorpions. Venezuelan Tityus species have been organized by González-Sponga into three artificial morphological groups, "androcottoides", "discrepans", and "nematochirus", based on the array of ventral carinae in metasomal segments II-IV. We also incorporated a fourth morphological group ("Tityus clathratus"), recently documented in Venezuela. Our results do not support the clustering of the species in the "androcottoides" and "discrepans" morphological groups, which include the majority of taxa of medical importance, but provided support for the "nematochirus" species group. T. clathratus was found to cluster with the Brazilian T. serrulatus and T. bahiensis. Divergence times of most clades are consistent with major events in the geological history of northern Venezuela and suggest that many Venezuelan Tityus species formed in the late Miocene and the Pliocene. In turn, we used the Tityus mtDNA phylogeny to determine the potential utility of phylogenetic systematics to predict Tityus venom antigenic reactivity by testing the recognition of T. nororientalis, T. discrepans, T. zulianus, T. perijanensis, and T. clathratus venoms by anti-T. discrepans horse antibodies. Cross-reactivity was significantly higher for the closely related eastern (T. nororientalis) and central coastal (T. discrepans) species in comparison to the distantly related Andean (T. zulianus) and Perijá (T. perijanensis) species. Reactivity of T. clathratus low mol. mass toxic components towards anti-T. serrulatus and anti-T. discrepans antivenoms was low, suggesting that venom components produced by the subgenus Archaeotityus (which encompass "clathratus" species) diverge antigenically from other Tityus scorpions.

Tick subolesin is an ortholog of the akirins described in insects and vertebrates.

The tick protective antigen, subolesin, is a regulatory protein involved in the control of multiple cellular pathways. Subolesin is evolutionary conserved in invertebrates and vertebrates with sequence homology to akirins, a recently renamed group of proteins that were proposed to function as transcription factors in Drosophila and mice. The objective of this research was to provide evidence of the sequence and functional homology between tick subolesin and akirins. The phylogenetic analysis of subolesin and akirins showed that they are evolutionary conserved. The effect of subolesin and akirin2 knockdown was compared in adult ticks and mice, respectively. The results demonstrated that tick subolesin is an ortholog of insect and vertebrate akirins and suggested that these proteins function in the regulation of NF-kappaB-dependent and independent expression of signal transduction and innate immune response genes. These results suggest that these proteins have an important role in host-pathogen interactions.

Trivalent antigens for degranulation of mast cells.

Degranulation of basophils and mast cells plays a central role in allergic reactions. Degranulation is a response to cell surface receptor aggregation caused by association of receptors with antibodies bound to multivalent antigens. Tools used in studying this process have included small-molecule divalent antigens, but they suffer from weak signaling apparently due to small aggregate size. We have prepared trivalent antigens that allow formation of larger aggregates and potent responses from mast cells.

Allergenicity and immunochemical characterization of six varieties of Olea europaea.

BACKGROUND: The inhalation of Olea europaea pollen is one of the most important causes of allergic respiratory diseases in the Mediterranean basin. The objective of this study was to investigate the antigenic and allergenic composition of six different O. europaea varieties collected in southern Spain. METHODS: The varieties included in the study were: Acebuche (wild olive), Carrasqueño, Nevado, Hojiblanco, Manzanillo and Picual. Extracts of these six varieties were prepared. Twenty-nine olive individuals with an immunoglobulin(Ig)E-mediated allergy to olive pollen were skin tested with these extracts. The antigenic profile of these extracts was evaluated by SDS-PAGE; the allergenic profile was investigated by immunoblotting using the serum of these 29 individuals. The Ole e 1 content was established by ELISA inhibition using purified Ole e 1 and rabbit polyclonal antibodies and by scanning densitometry. RESULTS: The extracts that induced the smallest wheal size were Acebuche and Hojiblanco, being significantly different from the rest of the extracts. The antigenic and allergenic profiles of the extracts also varied. The Ole e 1 content ranged from 0.050 in Hojiblanco to 0.232 in Manzanillo, measured by ELISA inhibition and from 0.153 in Hojiblanco to 0.677 in Nevado, measured by scanning densitometry. CONCLUSIONS: The different varieties of O. europaea pollen studied demonstrated great differences in the in vivo and in vitro potency of the extracts. There were significant differences in the Ole e 1 content, while the protein content remained very similar in these extracts. This study confirms previous observations of a great variability in the antigenic and allergenic composition of O. europaea pollen extracts and establishes significant differences in Ole e 1 content.

Infecções respiratórias agudas virais em crianças de Salvador: análise antigênica e genômica dos virus sincicial respiratório e adenovirus isolados com correlação clínica / Viral acute respiratory infections in childrens from Salvador: antigenic and genomics analysis of isolates of respiratory syncytial virus and adenovirus with clinic correlation

O presente estudo foi desenvolvido com o objetivo de contribuir para o conhecimento da prevalência viral em casos de infecções respiratórias agudas (IRA) em crianças de Salvador, assim como realizar a caracterização antigênica e genômica dos adenovírus e vírus sincicial respiratório (VSR) isolados. Um total de 482 casos de infecção respiratória aguda do ano de 1998 foram investigados quanto a etiologia viral através de imunofluorescência indireta e isolamento em cultura celular. Trinta adenovírus isolados em 1998, 1997 e 1996 foram submetidos soroneutralização e análise de restrição enzimática. Imunofluorescência indireta e ELISA foram utilizados para caracterização antigênica de VSR detectados em 1998 e 1999, respectivamente. A caracterização genômica de VSR foi realizada através da amplificação do gene da proteína G e posterior seqüenciamento de nucleotídeos. Cento e cinquenta e quatro casos de infecção respiratória aguda tiveram sua etiologia viral diagnosticada. Os vírus mais prevalentes em ordem decrescente foram o VSR, influenza A, parainfluenza 3, adenovírus, influenza B e parainfluenza 1. As IRA virais acometeram principalmente crianças até um ano de idade, do sexo masculino, e foram diagnosticadas predominantemente como infecção de vias aéreas superiores. Dos 30 Adenovírus analisados, dezoito eram Ad2, seis Adl, cinco Ad3 e um Ad5. A caracterização genômica dos Ad2 mostrou que circularam o genotipo D5 e uma nova variante genômica. Entre os Ad 1, circularam o genotipo DI e duas novas variantes genômicas. Representantes dos Ad3 e Ad5 foram os tipos genômicos 3f e 5#, respectivamente. Entre 84 VSR detectados em 1998,64 pertenciam ao grupo A e 14 ao grupo B. A análise genômica de 6 cepas de VSR mostrou a existência de vários genótipos circulantes em 1999. O VSR foi o vírus mais prevalente entre sete vírus investigados. Durante o mesmo período epidêmico houve a circulação de ambos...

Novel classes of fatty acid and retinol binding protein from nematodes.

Parasitic nematodes have recently been found to produce proteins which represent two new classes of fatty acid and retinoid binding protein. The first is the nematode polyprotein allergens/antigens (NPAs) which, as their name suggests, are synthesised as large polyproteins which are subsequently cleaved at regularly spaced sites to form multiple copies of a fatty acid binding protein of approximately 14.5 kDa. Binding studies using molecular environment-sensitive fluorescent ligands have shown that the binding site is highly unusual, producing blue-shifting in fluorescence to an unprecedented degree, suggesting a remarkably non-polar environment and isolation from solvent water. Computer-based structural predictions and biophysical observations have identified the NPAs as highly helical proteins which might form a four helix bundle, so constitute a new class of lipid binding protein from animals. The second class, like the NPAs, binds both fatty acids and retinol, but with a higher affinity for the latter. These are also highly helical but are structurally distinct from the NPAs. The biological function of these new classes of protein are discussed in the context of both the metabolic requirements of the parasites and the possible role of the proteins in control of the immune and inflammatory environment of the tissue sites parasitised.

Antígenos / Antigens

Los antígenos son compuestos de diversa naturaleza química provenientes del medio o generados por el propio organismo que son capaces de inducir una respuesta inmunológica en los vertebrados, propiedad denominada inmunogenicidad. La interacción del antígeno con los productos de la respuesta inmune, y especialmente con los anticuerpos, propiedad denominada antigenicidad, ha permitido conocer la estructura y función de numerosos antígenos, demostrándose que los productos de la respuesta inmune interactúan con regiones específicas del antígeno, denominadas epítopos, los cuales pueden corresponder a una secuencia aminoacídica determinada (epítopos lineales) o a un arreglo espacial de la cadena polipeptídica (epítopos conformacionales). Aunque la capacidad inmunogénica de un antígeno depende de su naturaleza química intrínseca (tamaño, forma, movilidad atómica, presencia de grupos químicos activos y residuos aromáticos) también está relacionada con la capacidad de respuesta del organismo y, en este sentido, son determinantes sus características genéticas y su historial inmunológico