Discussion. The fate of antigen

I should like to discuss an approach to the problem of immunological tolerance, which is closely akin to Burnet & Fenner’s (1949) ‘self-marker’ hypothesis, although its emphasis is less on the question of how antibodies are produced than on the detailed fate of potentially antigenic molecules when they leave the plasma and lymph and are catabolized. Dr Cinader’s figures certainly suggest that in tolerant rabbits heterologous albumin is eliminated from the plasma at rates which are substantially identical with those of homologous albumin. This is true also of heterologous plasma proteins in normal rabbits during the period before antibodies appear. Furthermore, we have found that in normal rats, in which albumin and globulin are eliminated at markedly different rates (Campbell, Cuthbertson, Matthews & McFarlane 1956), heterologous albumin behaves much like rat albumin and heterologous γ -globulin like rat γ -globulin for a week or more. It is a reasonable working hypothesis that foreign materials in the circulation are in the first place removed from the tissue fluids by the same mechanisms as deal with native materials possessing similar physico-chemical properties (e.g. molecular weight, surface charge). We are largely ignorant of what these mechanisms might be, except for the part played by reticulo-endothelial cells in removing particulate matter and denatured or aggregated proteins. However, the use by Coons, Leduc & Kaplan (1951) of fluorescent antibody to locate antigenic material in histological sections has shown that apparently undenatured proteins (e.g. bovine albumin, human γ -globulin) introduced into the plasma are detectable in immunologically active form within a wide variety of cells, such as renal tubule cells, liver parenchyma or vascular endothelium, in addition to cells of the reticuloendothelial system proper. There are possibly at least two processes going on concurrently: first, a non-selective ingestion of their surrounding fluid (with all that it contains) by cells which are widely distributed in the body, and are not necessarily confined to the reticulo-endothelial system. The mechanism may well be one of vacuolar ingestion (‘pinocytosis’), for which there is some circumstantial evidence, but which also presents difficulties. This would be one mechanism responsible for normal plasma protein catabolism. Secondly, there may be a selective removal of particulate or aggregated material, especially when negatively charged, by cells of the reticulo-endothelial system, notably by liver Küpffer cells.

1930 ◽  
Vol 26 (4) ◽  
pp. 438-438
Author(s):  
L. I. Vilensky

Meetings of medical societies. Society of Physicians at Kazan University. General Sessions Session 4 March 1930 L.I. Vilensky. Towards the doctrine of the intravital coloration of the reticuloendothelial system in experimental animals. On the basis of a study of 267 animals of various species (rabbits, rats, pigs, white mice, white rats and dogs) the vivo coloring of trypanblau, pyrrholblau, carmine and collargol, the author comes to the following conclusions: 1) All active cellular elements of the indifferent connective tissue that has retained the embryonic properties of the mesenchyme. 2) Teaching-Aschoff's, in the light of intravital coloration, should be expanded, as the teaching of an active mesenchyme, scattered throughout the body, but united by common physiological properties. 3) The process of gradual absorption of colloidal paint in individual elements of the reticulo-endothelial system has a certain pattern, which is exactly the same in different animals.


1956 ◽  
Vol 29 (4) ◽  
pp. 1369-1372
Author(s):  
G. A. Blokh ◽  
E. A. Golubkova ◽  
G. P. Miklukhin

Abstract One of the most important problems in the field of the physics and chemistry of rubber is that of vulcanization. Until now no single theory has been established, which elucidates the complex physico-chemical changes which occur during this process. Still more obscure has been the mechanism of the action of vulcanization accelerators, which, as is well known, not only reduce the time and the temperature of vulcanization, but also influence the physico-mechanical and chemical properties of the rubber. Most investigators have assumed that in the acceleration process a reaction with sulfur converts it to an active form which is capable of bringing about vulcanization at a lower temperature and at a greater rate, than with ordinary elemental sulfur in the absence of an accelerator. This point of view is based on the experimental fact that the vulcanization of rubber by sulfur dioxide and hydrogen sulfide, for example, which form sulfur in the nascent condition, proceeds rapidly even at room temperature. Investigators have also assumed that in the vulcanization process activation of sulfur in the presence of accelerators may occur by different mechanisms. It is possible that the accelerator, reacting with elemental sulfur, forms unstable intermediate compounds, which decompose with liberation of sulfur in an active form. The latter reacts with rubber, and the regenerated accelerator reacts again with elemental sulfur, etc. However, a different process is possible for the activation of elemental sulfur. By this second mechanism the unstable combination of accelerator and sulfur reacts directly with rubber without the formation of active sulfur. Both these mechanisms necessarily assume the formation of intermediate unstable combinations of the accelerator with sulfur. However, direct, experimentally-based demonstrations of such an interaction are lacking in the literature. There exist only theoretical hypotheses concerning the nature of the possible intermediate combination of the accelerator with sulfur. According to Ostromislensky's concepts, further developed by Bedford, such an intermediate compound has the character of a polysulfide. According to Bruni and Romani, this intermediate compound is a disulfide. As is well known, the disulfide theory was placed in doubt by Zaide and Petrov on the basis of data from the vulcanization of rubber in the presence of benzothiazolyl disulfide.


2014 ◽  
Vol 13 (1) ◽  
pp. 135-144
Author(s):  
I. V. Mitrofanova ◽  
I. V. Milto ◽  
I. V. Suhodolo ◽  
G. Yu. Vasyukov

Nanomaterials  –  materials,  whouse  structure  elements  has  proportions  doesn’t  exceed  100  nm.  In superdispersed state matter acquire new properties. In the last decade, carbon nanotubes become the most popular nanomaterials, that cause attention of representatives of various scientific field. The сarbon nanotubes offer new opportunities for biological and medical applications: imaging at the molecular, cellular and tissue levels, biosensors and electrodes based on carbon nanotubes, target delivery of various substances, radiation and photothermal therapy. The most promising of carbon nanotubes in the context of biomedical applications is their ability to penetrate the various tissues of the body and carry large doses of agents, providing diagnostic and therapeutic effects. Functionalized nanotubes are biodegradable. Other current direction of using carbon nanotubes in medicine and biology is to visualize objects on the molecular, cellular and tissue level. Associated with carbon nanotubes contrasting substances improve the visualization of cells and tissues, which can detected new patterns of development of the pathological process. Due to the vagueness of the question of biocompatibility and cytotoxicity of carbon nanotubes possibility of their practical application is hampered. Before the introduction of carbon nanotubes into practical health care is necessary to provide all the possible consequences of using nanotubes. High rates of properties and development of new nanostructures based on carbon nanotubes in the near future will lead to new advances related to the application and development of new parameters that will determine their properties and effects. In these review attention is paid to the structure, physico-chemical properties of nanotubes, their functionalization, pharmacokinetics and pharmacodynamics and all aspects of using of carbon nanotubes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Čepa ◽  
Veronika Dejmková ◽  
Ladislav Lešetický ◽  
Ivan Jelínek ◽  
Stanislav Smrček ◽  
...  

AbstractUnconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physico-chemical properties, particularly affecting the central nervous system. The aim of the present study was to characterize bilirubin-10-sulfonate (ranarubin), a naturally occurring bile pigment, including determination of its mixed acidity constants (pKa*). Thanks to the presence of the sulfonic acid moiety, this compound is more polar compared to UCB, which might theoretically solve the problem with an accurate determination of the UCB pKa* values of its propionic acid carboxylic groups. Bilirubin-10-sulfonate was synthesized by modification of a previously described procedure; and its properties were studied by mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and circular dichroism (CD) spectroscopy. Determination of pKa* values of bilirubin-10-sulfonate and UCB was performed by capillary electrophoresis with low pigment concentrations in polar buffers. The identity of the synthesized bilirubin-10-sulfonate was confirmed by MS, and the pigment was further characterized by NMR, IR, and CD spectroscopy. The pKa values of carboxylic acid moieties of bilirubin-10-sulfonate were determined to be 5.02, whereas those of UCB were determined to be 9.01. The physico-chemical properties of bilirubin-10-sulfonate were partially characterized with low pKa* values compared to those of UCB, indicating that bilirubin-10-sulfonate cannot be used as a surrogate pigment for UCB chemical studies. In addition, using a different methodological approach, the pKa* values of UCB were found to be in a mildly alkaline region, confirming the conclusions of a recent critical re-evaluation of this specific issue.


2000 ◽  
Vol 350 (2) ◽  
pp. 429-441 ◽  
Author(s):  
Stuart M. PITSON ◽  
Richard J. D'ANDREA ◽  
Lucianne VANDELEUR ◽  
Paul A. B. MORETTI ◽  
Pu XIA ◽  
...  

Sphingosine 1-phosphate (S1P) is a novel lipid messenger that has important roles in a wide variety of mammalian cellular processes including growth, differentiation and death. Basal levels of S1P in mammalian cells are generally low, but can increase rapidly and transiently when cells are exposed to mitogenic agents and other stimuli. This increase is largely due to increased activity of sphingosine kinase (SK), the enzyme that catalyses its formation. In the current study we have purified, cloned and characterized the first human SK to obtain a better understanding of its biochemical activity and possible activation mechanisms. The enzyme was purified to homogeneity from human placenta using ammonium sulphate precipitation, anion-exchange chromatography, calmodulin-affinity chromatography and gel-filtration chromatography. This resulted in a purification of over 106-fold from the original placenta extract. The enzyme was cloned and expressed in active form in both HEK-293T cells and Escherichia coli, and the recombinant E. coli-derived SK purified to homogeneity. To establish whether post-translational modifications lead to activation of human SK activity we characterized both the purified placental enzyme and the purified recombinant SK produced in E. coli, where such modifications would not occur. The premise for this study was that post-translational modifications are likely to cause conformational changes in the structure of SK, which may result in detectable changes in the physico-chemical or catalytic properties of the enzyme. Thus the enzymes were characterized with respect to substrate specificity and kinetics, inhibition kinetics and various other physico-chemical properties. In all cases, both the native and recombinant SKs displayed remarkably similar properties, indicating that post-translational modifications are not required for basal activity of human SK.


2018 ◽  
Vol 15 (144) ◽  
pp. 20180364 ◽  
Author(s):  
Stuart T. Johnston ◽  
Matthew Faria ◽  
Edmund J. Crampin

Nanoparticles provide a promising approach for the targeted delivery of therapeutic, diagnostic and imaging agents in the body. However, it is not yet fully understood how the physico-chemical properties of the nanoparticles influence cellular association and uptake. Cellular association experiments are routinely performed in an effort to determine how nanoparticle properties impact the rate of nanoparticle–cell association. To compare experiments in a meaningful manner, the association data must be normalized by the amount of nanoparticles that arrive at the cells, a measure referred to as the delivered dose. The delivered dose is calculated from a model of nanoparticle transport through fluid. A standard assumption is that all nanoparticles within the population are monodisperse, namely the nanoparticles have the same physico-chemical properties. We present a semi-analytic solution to a modified model of nanoparticle transport that allows for the nanoparticle population to be polydisperse. This solution allows us to efficiently analyse the influence of polydispersity on the delivered dose. Combining characterization data obtained from a range of commonly used nanoparticles and our model, we find that the delivered dose changes by more than a factor of 2 if realistic amounts of polydispersity are considered.


Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 634 ◽  
Author(s):  
Marziyeh Ajdary ◽  
Mohammad Moosavi ◽  
Marveh Rahmati ◽  
Mojtaba Falahati ◽  
Mohammad Mahboubi ◽  
...  

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.


Author(s):  
Victor J. Hruby ◽  
Terry O. Matsunaga

The tremendous advances in the development of methods for the design and synthesis of peptides. pseudo-peptides and related compounds, as well as the corresponding advances in our understanding of peptide and protein structure, conformation, topography, and dynamics provides unique opportunities to apply designed synthetic peptides for an enormous variety of problems in chemistry, biology, and medicine. In addition, if these advances can be coupled to the advances in molecular biology and the human genome project, on the one hand, and asymmetric synthesis and catalysis, on the other, it should be possible to provide hitherto unavailable, indeed unthinkable, approaches to diverse areas of drug design, behavioral neuroscience, molecular immunology, chemotherapy, and a wide variety of other uses. Already it is clear that peptide therapy has enormous potential in such diverse areas as growth control, blood pressure management, neurotransmission, hormone action, satiety, addiction, pain, digestion, reproduction, and so forth. Nature has “discovered” that it can control nearly all biological processes by various kinds of molecular recognition, and that peptides and proteins are uniquely suited for this control because of their enormous potential for diversity and their unique physico-chemical properties. This finding may, perhaps, be most readily understood if one recognizes that, considering only the 20 normal eukaryotic amino acids, the number of unique chemical entities for a pentapeptide is 3,200,000 (205), for a hexapeptide it is 64,000,000 (206), and so on. Considered from this perspective, perhaps it is not unexpected that Nature has “discovered” that peptides and proteins can do it all, from providing structure and motion, to catalysis, to information transduction, to growth and maturation, and so on. The ability of the immune system in higher animals, including humans, to recognize literally millions of foreign materials made by Nature as well as humans, and to get rid of them as part of its survival strategy, is just one example that illustrates the potential of peptide-based drugs, therapeutics, and modulators of biological function. Despite the enormous potential of peptides and small proteins for these areas, surprisingly little advantage has been taken of the potential of these molecules as drugs and tools for use in basic and clinical research.


1938 ◽  
Vol 38 (3) ◽  
pp. 273-278 ◽  
Author(s):  
R. Th. Scholtens

In an article (Scholtens, 1937) published elsewhere, I have shown that the external smooth properties of typhoid bacilli (stability in physiological salt solution and colony form) depend on the body antigens, not only on the O antigen but also on the Vi antigen.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3253
Author(s):  
Kinga Kazimierska ◽  
Urszula Kalinowska-Lis

Milk and colostrum have high biological potential, and due to their natural origin and non-toxicity, they have many uses in cosmetics and dermatology. Research is ongoing on their potential application in other fields of medicine, but there are still few results; most of the published ones are included in this review. These natural products are especially rich in proteins, such as casein, β-lactoglobulin, α-lactalbumin, lactoferrin, immunoglobulins, lactoperoxidase, lysozyme, and growth factors, and possess various antibacterial, antifungal, antiviral, anticancer, antioxidant, immunomodulatory properties, etc. This review describes the physico-chemical properties of milk and colostrum proteins and the natural functions they perform in the body and compares their composition between animal species (cows, goats, and sheep). The milk- and colostrum-based products can be used in dietary supplementation and for performing immunomodulatory functions; they can enhance the effects of certain drugs and can have a lethal effect on pathogenic microorganisms. Milk products are widely used in the treatment of dermatological diseases for promoting the healing of chronic wounds, hastening tissue regeneration, and the treatment of acne vulgaris or plaque psoriasis. They are also increasingly regarded as active ingredients that can improve the condition of the skin by reducing the number of acne lesions and blackheads, regulating sebum secretion, ameliorating inflammatory changes as well as bestowing a range of moisturizing, protective, toning, smoothing, anti-irritation, whitening, soothing, and antiaging effects.


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