scholarly journals IgA: Structure, Function, and Developability

Antibodies ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 57 ◽  
Author(s):  
Patrícia de Sousa-Pereira ◽  
Jenny M. Woof

Immunoglobulin A (IgA) plays a key role in defending mucosal surfaces against attack by infectious microorganisms. Such sites present a major site of susceptibility due to their vast surface area and their constant exposure to ingested and inhaled material. The importance of IgA to effective immune defence is signalled by the fact that more IgA is produced than all the other immunoglobulin classes combined. Indeed, IgA is not just the most prevalent antibody class at mucosal sites, but is also present at significant concentrations in serum. The unique structural features of the IgA heavy chain allow IgA to polymerise, resulting in mainly dimeric forms, along with some higher polymers, in secretions. Both serum IgA, which is principally monomeric, and secretory forms of IgA are capable of neutralising and removing pathogens through a range of mechanisms, including triggering the IgA Fc receptor known as FcαRI or CD89 on phagocytes. The effectiveness of these elimination processes is highlighted by the fact that various pathogens have evolved mechanisms to thwart such IgA-mediated clearance. As the structure–function relationships governing the varied capabilities of this immunoglobulin class come into increasingly clear focus, and means to circumvent any inherent limitations are developed, IgA-based monoclonal antibodies are set to emerge as new and potent options in the therapeutic arena.

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Lisa C. Lindesmith ◽  
Martina Beltramello ◽  
Jesica Swanstrom ◽  
Taylor A. Jones ◽  
Davide Corti ◽  
...  

Abstract Background.  Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods.  Immunoglobulin (Ig)A was purified from sera collected from GI.1-infected participants, and potential neutralization activity was measured using a surrogate neutralization assay based on antibody blockade of ligand binding. Human and mouse monoclonal antibodies (mAbs) were produced to multiple GI VLPs to characterize GI epitopes. Results.  Immunoglobulin A purified from day 14 post-GI.1 challenge sera blocked binding of GI.1, GI.3, and GI.4 to carbohydrate ligands. In some subjects, purified IgA preferentially blocked binding of other GI VLPs compared with GI.1, supporting observations that the immune response to GI.1 infection may be influenced by pre-exposure history. For other subjects, IgA equivalently blocked multiple GI VLPs. Only strain-specific mAbs recognized blockade epitopes, whereas strain cross-reactive mAbs recognized nonblockade epitopes. Conclusions.  These studies are the first to describe a functional role for serum IgA in norovirus immunity and the first to characterize human monoclonal antibodies to GI strains, expanding our understanding of norovirus immunobiology.


2017 ◽  
pp. 85-88
Author(s):  
O.I. Ostapenko ◽  
◽  
V.P. Kvashenko ◽  
I.K. Akimova ◽  
I.N. Nosova ◽  
...  

The objective: the study of immunomodulatory effects of a probiotic, which contains lyophilized Lactobacillus (Lactobacillus rhamnosus) – 13 mg (2,0ґ109 CFU) and lyophilized bifidobacteria (Bifidobacterium lactis) – 4 mg (2,0ґ109 CFU) the level of serum immunoglobulin IgA as a marker of local immunity in the plasma of women of reproductive age with the violation of the biocenosis of the vagina. Patients and methods. The study involved 86 patients of reproductive age with the violation of the vaginal biocenosis, which were divided into two groups according to received treatment. A survey was conducted for all patients in both groups: determine the level of serum IgA, measuring pH of vaginal environment and the quantification of lactobacilli and pathogenic flora with the help of test-system «Florotsenoz» before treatment and in 6 weeks after treatment. The state of vaginal microbiocenosis in both groups before treatment was homogeneous. Patients in both groups as therapy at the first stage of treatment received, if necessary antimicrobial therapy depending on the selected flora. In the second stage (restoration of microflora) patient of the main group received systemic probiotic combined with a complex prebiotic local action, patients in the control group, the probiotic localy in the form of the vaginal candles or tablets. Results. The research stated the increasing level of serum IgA in blood plasma of patients of the main group compared to control group at 20%, normalizing the pH of the vaginal environment in the main group in 94% of cases, which indicates an increase of immunity in mucosal. Conclusion. The inclusion of the systemic probiotic in the scheme of treatment of disorders of biocenosis of the vagina system enhances the increasing of immunity of the mucous membranes, and the vaginal tablets prebiotic of local action restores the own normal microflora of the vagina. Key words: serum immunoglobulin A, local immunity, vaginal dysbiosis, probiotics, prebiotics, vaginal microbiocenosis, the pH of the vaginal environment.


1986 ◽  
Vol 32 (10) ◽  
pp. 1832-1835 ◽  
Author(s):  
P C Patel ◽  
L Aubin ◽  
J Côte

Abstract We investigated two techniques of immunoblotting--the Western blot and the dot blot--for use in detecting prostatic acid phosphatase (PAP, EC 3.1.3.2). We used polyclonal antisera to human PAP, produced in rabbits by hyperimmunization with purified PAP, and PAP-specific monoclonal antibodies in the immunoenzymatic protocols. We conclude that PAP can be readily detected by Western blots with use of polyclonal antisera, but not with monoclonal antibodies. On the other hand, using a dot blot assay, we could easily detect PAP with both polyclonal and monoclonal antibodies.


1992 ◽  
Vol 267 (21) ◽  
pp. 14654-14661
Author(s):  
T Restle ◽  
M Pawlita ◽  
G Sczakiel ◽  
B Müller ◽  
R.S. Goody

1989 ◽  
Vol 2 ◽  
pp. 175-183 ◽  
Author(s):  
Daniel J. Chure

“Although I work a lot with fossils in my own research on fishes, I do not care to be called a paleontologist; and I am turned off by many aspects of the public-relations hoopla surrounding paleontology, especially dinosaurs…. One could easily argue that the schools' fascination with dinosaurs might also detract from the other aspects of earth science and biological science and, in the end, weaken paleontology's image as an activity for hard-nosed grown-ups.”K.S. Thomson, 1985: p. 73“Let dinosaurs be dinosaurs. Let the Dinosauria stand proudly alone, a Class by itself. They merit it. And let us squarely face the dinosaurness of birds and the birdness of the Dinosauria. When the Canada geese honk their way northward, we can say: “The dinosaurs are migrating, it must be spring!”R.T. Bakker, 1986: p. 462It is a now oft-repeated statement that we are in the Second Golden Age of dinosaur studies. This may at first seem to be yet another overstatement by dinosaur fanatics; in fact, it is substantiated on a number of fronts. Research activity is certainly at an all-time high, with resident dinosaur researchers on every continent (except Antarctica) and dinosaurs known from every continent (including Antarctica). This activity has resulted in a spate of discoveries, including not only new genera and species, but entirely new types of dinosaurs, such as the segnosaurs. Well-known groups are producing surprises, such as armored sauropods and sauropods bearing tail clubs. Good specimens of previously named genera are revealing unsuspected structural features that almost defy explanation, as in the skull of Oviraptor. However, dinosaur studies extend far beyond the traditional emphasis on dinosaur morphology, and encompass paleobiogeography, paleoecology, taphonomy, physiology, tracks, eggs, histology, and extinction, among others. In some cases, several of these studies can be applied to a single taxon or locality to give us a fairly detailed understanding of the paleobiology of some species.


1987 ◽  
Author(s):  
E Delain ◽  
M Barrav ◽  
J Tapon-Bretaudière ◽  
F Pochon ◽  
F Van Leuven

Electron microscopy is a very convenient method to localize the epitopes of monoclonal antibodies (mAbs) at the surface of macromolecules for studying their tree-dimensional organization.We applied this immuno-electron microscopic method to human ct2-macroglobulin (ct2M). 29 anti-α2M mAbs have been tested with the four different forms of a2M : native and chymotrypsin-transformed tetramers, and the corresponding dimers, obtained by dissociation with divalent cations. These mAbs can be classified in three types : those which are specific for 1) the H-like transformed molecules, 2) the native molecules, and 3) those which can react with both forms of α2M.1) Among the H-like α2M specific mAbs, several react with the 20 kD-domain which is recognized by the cellular receptor of transformed a2M. This domain is located at the carboxyterminal end of each monomer. One IgG binds to the end of two adjacent tips of the H-like form.The other mAbs of this type bind to the α2M tips at non-terminal positions. Intermolecular connections built polymers of alternating α2M and IgG molecules.2) Among the native a2M-specific mAbs some are able to inhibit the protease-induced transformation of the native α2M. The binding sites of these mAbs are demonstrated on the native half-molecules. One of these mAbs was also able to react with transformed dimers, in a region corresponding very likely to an inaccessible epitope in the tetrameric transformed α2M molecule.3) Among the mAbs of this type, only two were able to inhibit the protease-induced transformation of α2M. Obviously, their epitopes should be close to the bait region of α2M. The other mAbs reacting with both α2M forms did not inhibit the α2M transformation.All these mAbs can be distinguished by the structure of the immune complexes formed with all forms of α2M. The epitopes are more easily located on the dimers and on the H-like transformed α2M than on the native molecules.From these observations, we propose a new model of the tree-dimensional organization of the human α2M in its native and transformed configurations, and of its protease-induced transformation.


2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
Giuseppe Sautto ◽  
Nicasio Mancini ◽  
Giacomo Gorini ◽  
Massimo Clementi ◽  
Roberto Burioni

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminaryin vitroandin vivomodels of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.


Perception ◽  
1996 ◽  
Vol 25 (12) ◽  
pp. 1419-1436 ◽  
Author(s):  
Paul Locher ◽  
Sharon Gray ◽  
Calvin Nodine

Two experiments were performed to examine how the subjective balance of a painting is created by its structural features and to determine if balance influences the way people look at paintings. Stimuli consisted of sixteen reproductions of twentieth-century paintings varying in artistic style and a reconstructed less-balanced version of each. Participants in experiment 1 determined the location of the balance center of each composition, assigned ‘weights’ to the pictorial features which contributed to the location of the balance center, and rated the picture for balance. It was found that design and museum professionals and individuals untrained in the visual arts were in good agreement as to the structural framework underlying the balance organization of a painting. For all participants, disruption of the balanced organizations of the original compositions led to reliable shifts in the location of the perceived balance centers of the originals compared with their less-balanced perturbations. Additionally, it was observed that particular features as such were not the origin of the balance phenomenon; rather, judgments concerning the balance structure and its center were dependent on the global integration of information across a wide area of the display field, but especially from its central region. Last, the subtle changes in balance structure between versions resulted in lower ratings of balance being assigned to the less-balanced perturbations by the design professionals only; the other two participant groups evaluated overall balance of the versions as comparable. In experiment 2, eye movements of a different group of untrained individuals were recorded as they performed similar tasks on the art stimuli. It was found that disruption of the balance structure of the original representational but not abstract compositions resulted in different regions of the original and perturbed versions being visually explored. Findings of both experiments are related to theoretical notions of balance.


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