Antigen and superantigen presentation as defined by the MHCII-accessory proteins and associated-peptides

MHCII molecules expose a weave of antigens, which send survival or activation signals to T lymphocytes. The ongoing process of peptide binding to the MHC class II groove implicates three accessory molecules: the invariant chain, DM and DO. The invariant chain folds and directs the MHCII molecules to the endosomal pathway. Then, DM exchanges the CLIP peptide, which is a remnant of the degraded invariant chain, for peptides of better affinity. Expressed in highly specialized antigen presenting cells, DO competes with MHCII molecules for DM binding and favors the presentation of receptor-internalized antigens. Altogether, these molecules exhibit potential immunomodulatory properties that can be exploited to increase the potency of peptide vaccines. DO requires DM for maturation and to exit the ER. Interestingly, it is possible to monitor this interaction through a conformation change on DOβ that is recognized by the Mags.DO5 monoclonal antibody. Using Mags.DO5, we showed that DM stabilizes the interactions between the DO α1 and β1 chains and that DM influences DO folding in the ER. Thus, the Mags.DO5+ conformation correlates with DO egress from the ER. To further evaluate this conformation change, directed evolution was applied to DO. Of the 41 unique mutants obtained, 25% were localized at the DM-DO binding interface and 12% are at the solvent-exposed β1 domain, which is thought to be the Mags.DO5 epitope. In addition, I used the library to test the ability of HLA-DO to inhibit HLA-DM and sorted for the amount of CLIP. Interestingly, most of the mutants showed a decrease inhibitory effect, supporting the notion that the intrinsic instability of DO is a required for its function. Finally, these results support the model in which DO competes against classical MHCII molecules by sequestering DM chaperone’s function. MHCII molecules are also characterized by their ability to present superantigens, a group of bacterial or viral toxins that coerces MHCII-TCR binding in a less promiscuous fashion than what is observed in a canonical setting. While the mechanism of how bacterial superantigens form trimeric complexes with TCR and MHCII is well understood, the mouse mammary tumor virus superantigens (vSAG) are poorly defined. In the absence of a crystal structure, I chose a functional approach to examine the relation between vSAG, MHCII and TCR with the goal of uncovering the overall trimolecular architecture. I showed that TCR concomitantly binds both the MHCII α chain and the vSAG and that TCR-MHCII docking is almost canonical when coerced by vSAGs. Because many peptides may be tolerated in the MHCII groove, the pressure exerted by vSAG seems to tweak conventional TCR-MHCII interactions. Furthermore, my results demonstrate that vSAG binding to MHCII molecules is conformation-dependent and abrogated by the CLIP amino-terminal residues extending outside the peptide-binding groove. In addition, they also suggest that vSAGs cross-link adjacent MHCIIs and activate T cells via a TGXY motif.

The genome of Rhizobium leguminosarum has recognizable core and accessory components

Background: Rhizobium leguminosarum is an alpha-proteobacterial N-2-fixing symbiont of legumes that has been the subject of more than a thousand publications. Genes for the symbiotic interaction with plants are well studied, but the adaptations that allow survival and growth in the soil environment are poorly understood. We have sequenced the genome of R. leguminosarum biovar viciae strain 3841. Results: The 7.75 Mb genome comprises a circular chromosome and six circular plasmids, with 61% G+C overall. All three rRNA operons and 52 tRNA genes are on the chromosome; essential protein-encoding genes are largely chromosomal, but most functional classes occur on plasmids as well. Of the 7,263 protein-encoding genes, 2,056 had orthologs in each of three related genomes ( Agrobacterium tumefaciens, Sinorhizobium meliloti, and Mesorhizobium loti), and these genes were overrepresented in the chromosome and had above average G+C. Most supported the rRNA-based phylogeny, confirming A. tumefaciens to be the closest among these relatives, but 347 genes were incompatible with this phylogeny; these were scattered throughout the genome but were over-represented on the plasmids. An unexpectedly large number of genes were shared by all three rhizobia but were missing from A. tumefaciens. Conclusion: Overall, the genome can be considered to have two main components: a 'core', which is higher in G+C, is mostly chromosomal, is shared with related organisms, and has a consistent phylogeny; and an 'accessory' component, which is sporadic in distribution, lower in G+C, and located on the plasmids and chromosomal islands. The accessory genome has a different nucleotide composition from the core despite a long history of coexistence.

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution.

Digital dermatitis of the accessory digits of dairy cows

Esse estudo caracteriza lesões de dermatite digital (DD) nos dígitos acessórios de vacas leiteiras, além de apresentar a terapia aplicada. Foram utilizados 15 bovinos leiteiros da raça Holandês com DD nos dígitos acessórios dos membros pélvicos. Os animais eram provenientes de quatro fazendas leiteiras com histórico prévio de dermatite digital (DD). Todos os quinze animais foram tratados da mesma forma: após excisão das lesões e sutura das feridas cutâneas, aplicou-se oxitetraciclina pó topicamente sob bandagem e oxitetraciclina (20mg/kg) de longa ação, via intramuscular. Obtiveram-se amostras de tecidos para histopatologia, inclusive por microscopia eletrônica de transmissão (MET). Observou-se cicatrização em todos os animais após 15 dias do procedimento cirúrgico. A maioria das lesões macroscópicas foram projeções papilomatosas ou em forma de verrugas. Os achados histopatológicos de todas as amostras revelaram hiperplasia da epiderme com hiperceratose, inúmeras mitoses no estrato basal, com invasões alongadas em forma de rede na derme superficial e intermediária. A MET evidenciou organismos com formas longas, afiladas e espiraladas, presumivelmente espiroquetas. Tanto as características morfológicas, quanto a resposta à terapia das lesões foram comparáveis às descritas para DD.

Accessory Nuclei in the Oocytes of Pachycondyla (Neoponera) villosa (Hymenoptera: Ponerinae) as a Source of Annulate Lamellae

In insects' oocytes, structures called accessory nuclei can be observed. They are similar to the nucleus of the oocyte and have been detected in Hymenoptera as well as in other groups, with their source and functions still under discussion (Cassidy & King 1972). Through the use of histochemical techniques as well as ultrastructural ones, it was possible to observe several accessory nuclei surrounding the oocyte nucleus in the immature oocytes of Pachycondyla (Neoponera) villosa ants. Morphologically they were seen to be round and smaller than the germinal vesicle. When using these histochemical techniques, the only positive reaction was for proteins. Ultrastructurally they have the same morphology as the oocyte nucleus and a fine and electrondense granulation was observed inside them. The function of accessory nuclei in P (Neoponera) villosa is probably as a source of anullate lamellae and as an RNA reservoir in the oocytes. In mature oocytes (stage III), these structures are not observed, suggesting that they disappeared before this stage by releasing their contents into the oocytes' cytoplasm, according to Camargo-Mathias and Caetano (1993).

HYPERANDROGENISM DUE TO 3-BETA-HYDROXYSTEROID DEHYDROGENASE-DEFICIENCY WITH ACCESSORY ADRENOCORTICAL TISSUE - A HORMONAL AND METABOLIC EVALUATION

1. Adrenal ectopic tissue has been detected in the paragonadal region of normal women. In patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, the manifestation of hyperplasia of paragonadal accessory adrenal tissue has been usually reported to occur in males. Probably, this is the first report of a female with 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency with ectopic adrenal tissue in ovaries. However, the occurrence of hyperplasia of adrenal rests among women with classical congenital adrenal hyperplasia may not be rare, especially among patients with a late diagnosis.2. We report a woman with 3beta-HSD deficiency whose definitive diagnosis was made late at 41 years of age immediately before surgery for the removal of a uterine myoma. During surgery, exploration of the abdominal cavity revealed the presence of bilateral accessory adrenal tissue in the ovaries and in the para-aortic region. The patient had extremely high levels of ACTH (137 pmol/l), DHEA (901.0 nmol/l), DHEA-S (55.9 mumol/l), androstenedione (70.2 nmol/l), testosterone (23.0 nmol/l) and 17alpha-hydroxypregnenolone (234.4 nmol/l) suggesting 3beta-HSD deficiency.3. In view of these elevated androgen levels, with an absolute predominance of DHEA and DHEA-S, we evaluated the effect of this hormonal profile on carbohydrate tolerance and insulin response to glucose ingestion.4. The patient presented normal glucose tolerance but her insulin response was lower than that of 14 normal women (area under the curve, 3beta-HSD = 17,680 vs 50,034 pmol/l for the control group over a period of 3 h after glucose ingestion).5. These results support recent data suggesting that patients with increased serum DHEA and DHEA-S levels do not present resistance to insulin.

Microscopical aspects od accessory air breathing through a modified stomach in the armoured catfish Liposarcus anisitsi (Siluriformes, Loricariidae)

The presence of an accessory air breathing mechanism as verified by several authors, is widespread among Loricariidae, where modified parts of the digestive tract act primarily as oxygen-exchange organs. An anatomical and histological analysis was carried out on the stomach and intestine of the armoured catfish Liposarcus anisitsi. The data support the assumption that the modified stomach is responsible for holding air and allows blood oxygenation under hypoxia. Experiments demonstrating survival of air breathing Liposarcus in severely hypoxic water support the hypothesis and are discussed.

THE HYPOPHYSEAL-TESTICULAR AXIS AND SEX ACCESSORY-GLANDS FOLLOWING CHEMICAL SYMPATHECTOMY WITH GUANETHIDINE OF PRE-PUBERTAL TO MATURE RATS

Selective chemical sympathectomy of the internal sex organs of prepubertal to mature male Wistar rats was performed by chronic treatment with low doses of guanethidine. Plasma testosterone and luteinizing hormone and the intratesticular level of testosterone were determined. The weight and fructose content of seminal vesicle and ventral prostate were also investigated. The results showed that sympathetic innervation is related to the control of the hypophyseal-testicular axis as well as to the growth and potential secretory activity of the male sex accessory glands.

Prevalence of different types of accessory canals in the furcation area of third molars

Background: Although there are several studies that show the prevalence and diameter of accessory root canals in the furcation area, there is a scarceness of studies that observe the trajectory and different types of cavo-interradicular canals. The aim of this study was to verify the prevalence of the different morphologic types of accessory canals in the furcation region in an attempt to show their trajectories.Methods: Forty submerged mandibular third molars were used, which were extracted and decalcified so that the microtomy procedure in the mesio-distal axial plane could be performed, obtaining semiserial sections with thicknesses of 5 mu m. The sections were stained with hematoxylin and eosin and observed under optical microscopy.Results: All of the morphologic types were found, whereas the proper accessory canals, type-A canals, were present in 10% of the specimens. The most prevalent canals were the sealed ones (type D), with a prevalence of 87.5%, followed by the blind ones (type B), with a prevalence of 75%. The loop accessory canals (type C), observed in only 5% of the teeth, were the least prevalent ones.Conclusions: Different morphologic types of accessory canals were found in the furcation area of submerged mandibular molars. The histologic method was effective to show the canal trajectories.

Method for marginal measurements of restorations: accessory device for toolmakers microscope.

Standardization of measurements for marginal fit of castings is critical. This study describes the fabrication of a device that allowed fixation of specimens on a Toolmakers microscope with identical conditions according to tri-dimensional positioning of specimens, measuring location, and seating force. The device also allows mapping of the marginal discrepancies on the entire marginal perimeter of the tooth preparation.

Structure of the pelvic and penile urethra - Relationship with the ducts of the sex accessory glands of the Mongolian gerbil (Meriones unguiculatus)

The urethra is the main place of entry for sexually transmitted pathogens. However, there is little literature on the morphology of the urogenital system, principally the urethra and ducts of the sex accessory glands. The Mongolian gerbil is an insectivorous, herbivorous and monogamous rodent with nocturnal habits; it has been used successfully as a laboratory animal since the 1960s. Therefore, the objective of the present paper was to describe the structure and ultrastructure of the urethra and its relations to the ducts of the accessory sex glands of the Mongolian gerbil (Meriones unguiculatus), contributing to the understanding of the reproductive biology of the rodent and aiming to provide data for future experimental studies. Conventional techniques of light and scanning electron microscopy were utilized. The urethra and ducts of the accessory sex glands are similar to those of the albino rat and the mouse. However, there is variation in drainage type among accessory sex glands for the inner urethra. The ducts of the seminal vesicle, the ductus deferens, drain their contents independently into the ampullary duct that opens in the urethra. The ducts of the prostate, coagulating and bulbourethral glands drain their contents independently into the urethra.