scholarly journals Targeting the Gut Mucosal Immune System Using Nanomaterials

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1755
Author(s):  
Jacob McCright ◽  
Ann Ramirez ◽  
Mayowa Amosu ◽  
Arnav Sinha ◽  
Amanda Bogseth ◽  
...  

The gastrointestinal (GI) tract is one the biggest mucosal surface in the body and one of the primary targets for the delivery of therapeutics, including immunotherapies. GI diseases, including, e.g., inflammatory bowel disease and intestinal infections such as cholera, pose a significant public health burden and are on the rise. Many of these diseases involve inflammatory processes that can be targeted by immune modulatory therapeutics. However, nonspecific targeting of inflammation systemically can lead to significant side effects. This can be avoided by locally targeting therapeutics to the GI tract and its mucosal immune system. In this review, we discuss nanomaterial-based strategies targeting the GI mucosal immune system, including gut-associated lymphoid tissues, tissue resident immune cells, as well as GI lymph nodes, to modulate GI inflammation and disease outcomes, as well as take advantage of some of the primary mechanisms of GI immunity such as oral tolerance.

Author(s):  
Caterina Ledda ◽  
Claudia Lombardo ◽  
Elisabetta A. Tendi ◽  
Maria Hagnas ◽  
Gianluca Paravizzini ◽  
...  

: Fluoro-edenite (FE) is an asbestos-like amphibole present in the bentonitic lavas extracted from a stone quarry in Biancavilla, a village sited in the Etnean Volcanic Area (Italy). : Thoracic pathologies are the results of excessive inflammatory processes that are the early response of the immune system to inhaled fibers. As demonstrated for asbestos, fibers may trigger immune system cells in an acute and/or chronic manner. This review aims to clarify the pathways of inflammation in workers exposed to FE fibers. : Based on the articles reviewed, it seems that a permanent stimulus created by repeatedly inhaling the FE fibers and their persistence in the body can act as trigger both in promoting inflammatory processes and in immunological induction of autoimmune disease.


2005 ◽  
Vol 93 (S1) ◽  
pp. S41-S48 ◽  
Author(s):  
Maria Luisa Forchielli ◽  
W. Allan Walker

The newborn infant leaves a germ-free intrauterine environment to enter a contaminated extrauterine world and must have adequate intestinal defences to prevent the expression of clinical gastrointestinal disease states. Although the intestinal mucosal immune system is fully developed after a full-term birth, the actual protective function of the gut requires the microbial stimulation of initial bacterial colonization. Breast milk contains prebiotic oligosaccharides, like inulin-type fructans, which are not digested in the small intestine but enter the colon as intact large carbohydrates that are then fermented by the resident bacteria to produce SCFA. The nature of this fermentation and the consequent pH of the intestinal contents dictate proliferation of specific resident bacteria. For example, breast milk-fed infants with prebiotics present in breast milk produce an increased proliferation of bifidobacteria and lactobacilli (probiotics), whereas formula-fed infants produce more enterococci and enterobacteria. Probiotics, stimulated by prebiotic fermentation, are important to the development and sustainment of intestinal defences. For example, probiotics can stimulate the synthesis and secretion of polymeric IgA, the antibody that coats and protects mucosal surfaces against harmful bacterial invasion. In addition, appropriate colonization with probiotics helps to produce a balanced T helper cell response (Th1 = Th2 = Th3/Tr1) and prevent an imbalance (Th1 > Th2 or Th2 > Th1) contributing in part to clinical disease (Th2 imbalance contributes to atopic disease and Th1 imbalance contributes to Crohn's disease andHelicobacter pylori-induced gastritis). Furthermore, a series of pattern recognition receptors, toll-like receptors on gut lymphoid and epithelial cells that interact with bacterial molecular patterns (e.g. endotoxin (lipopolysaccharide), flagellin, etc.), help modulate intestinal innate immunity and an appropriate adaptive immune response. Animal and clinical studies have shown that inulin-type fructans will stimulate an increase in probiotics (commensal bacteria) and these bacteria have been shown to modulate the development and persistence of appropriate mucosal immune responses. However, additional studies are needed to show that prebiotics can directly or indirectly stimulate intestinal host defences. If this can be demonstrated, then prebiotics can be used as a dietary supplement to stimulate a balanced and an appropriately effective mucosal immune system in newborns and infants.


1999 ◽  
Vol 161 (1) ◽  
pp. 167-175 ◽  
Author(s):  
AM ten Bokum ◽  
EG Lichtenauer-Kaligis ◽  
MJ Melief ◽  
PM van Koetsveld ◽  
C Bruns ◽  
...  

Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter and may also have an immunomodulatory role. The genes for five subtypes of somatostatin receptors (sst) have been cloned, suggesting that the diverse effects of the peptide might be mediated by different receptors. We are interested in studying the role of sst ininflammation, using an animal model. Because of the up-regulation of sst expression in inflamed joints in human rheumatoid arthritis, we chose rat adjuvant arthritis as an experimental model. In order to determine which of the sst subtypes might be important in immune modulation, subtype expression in leukocytes isolated from different lymphoid tissues of the rat was studied. Also, the expression levels of the most abundantly expressed sst mRNAs in leukocytes from spleen and blood were compared in rats with adjuvantarthritis and controls, using a semi-quantitative approach. Furthermore, the effect of systemic administration of a long-acting somatostatin analogue, octreotide, which binds selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the severity of rat adjuvant arthritis, was studied. The main sst expressed in cells of the rat immune system, both resting and activated, were found to be sst3 and sst4. This contrasts with the human and murine situations, in which sst2 appears to be the main subtype expressed in the immune system. No quantitative differences in sst subtype mRNA levels in leukocytes from spleen and blood were found between rats with adjuvant arthritis and controls. Finally, no effect of systemic administration of octreotide on either the incidence or severity of adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat adjuvant arthritis corroborates our finding that these sst subtypes are not expressed in cells of the rat immune system. In conclusion, cells of the rat immune system appear to express a spectrum of sst (sst3 and sst4) different from that found in human granulomatous and autoimmune disease (mainly sst2). Therefore, the rat adjuvant arthritis model appears to be suitable only for studying the immunomodulatory effects of somatostatin analogues which have a high affinity for sst3 and sst4, but not for studying the immunomodulatory effects of octreotide, which has a high affinity only for sst2 and sst5.


Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 934-944
Author(s):  
A Hanninen ◽  
M Salmi ◽  
O Simell ◽  
D Andrew ◽  
S Jalkanen

The beta 7-integrin subunit can pair with two alpha-chains, alpha 4 and alpha E, and is expressed mainly on lymphocytes. As an alpha 4- heterodimer it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing receptor. As an alpha E-heterodimer it binds to E- cadherin and is mainly found on intestinal intraepithelial lymphocytes. Consequently, beta 7 is mostly expressed on lymphocytes of the mucosal immune system. To study the compartmentalization of these cells further we compared the distribution of such lymphocytes in two strains of mice (BALB/c and NOD) and found that the distribution of beta 7-positive lymphocytes among various lymphoid tissues in these strains was very different. In NOD mice a conspicuous population of beta 7- integrin(high) lymphocytes expressing either alpha 4, alpha E, or both, was found in nonmucosal lymphoid tissues such as peripheral lymph nodes (PLNs). They mostly expressed the PLN homing receptor L-selectin, and included both naive and memory cells on the basis of their expression of CD44/pgp-1 and CD45RB, as did the few beta 7(high) lymphocytes in BALB/c PLNs. Their homing to Peyer's patches (PPs) and PLNs was equally effective and the cells homing to PPs and PLNs were equal in their level of L-selectin and alpha 4/beta 7 expression. However, functional studies indicated that their homing to PPs mostly depended on alpha 4/beta 7-integrin, whereas they mainly used L-selectin to home to PLNs. beta 7(high) lymphocytes were found also in circulating blood of unmanipulated NOD mice, and their L-selectin expression was higher than in BALB/c mice. These results show that lymphocytes of the mucosal immune system may also express the peripheral node homing receptor L- selectin during their recirculation and that in NOD mice they frequently retain a dual homing specificity, which leads to their accumulation in nonmucosal tissues.


Author(s):  
V. I. Raitskaya

The drug Argovit developed in the LLC Vector-Vita Research and Production Center has antimicrobial and astringent properties, easily fits into the technology of housing farm animals and poultry in cases of uncomplicated colibacteriosis and is effective in isolated use, it is cheaper than other drugs, which makes it attractive in the modern market of biological products. The purpose of the research was to study the effectiveness of the drug Argovit for the treatment and prevention of gastrointestinal diseases of piglets in comparison with the basic drug Baitril used in the farm. Piglets of the experimental group (n=20) with the syndrome of gastrointestinal diseases have been treated with 1,0 % aqueous solution of the drug Argovit at a dose of 2 ml/kg of live weight 2 times a day until clinical recovery. The drug contributed to a lighter course and reduced the duration of the disease by half, while the livability of piglets reached 90,0 %. There was also a weakening of inflammatory processes in the body of piglets of both groups, which was characterized by the decrease in the level of leukocytes in piglets of the experimental group during treatment from 12,9±0,75 to 10,1±0,89×10⁹/l, and in the control group from 11,3±1,20 to 9,0±0,04×10⁹/l. The platelet content in animals at the beginning of the experiment was slightly higher than the lower limit of the norm in the experimental group by 1,8 %, in the control group by 4,7 %. At the same time, the restoration of homeostasis and the decrease in the level of protein in the blood serum have been observed. It has been found that the use of the drug Argovit to piglets during the suckling period and after weaning improves the morphological and biochemical parameters of blood due to the protective forces of protein by 4,7 %, reduces the phenomena of diarrhea, and as a result increases their livability.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 375 ◽  
Author(s):  
Hellfritzsch ◽  
Scherließ

Vaccine delivery via mucosal surfaces is an interesting alternative to parenteral vaccine administration, as it avoids the use of a needle and syringe. Mucosal vaccine administration also targets the mucosal immune system, which is the largest lymphoid tissue in the human body. The mucosal immune response involves systemic, antigen-specific humoral and cellular immune response in addition to a local response which is characterised by a predominantly cytotoxic T cell response in combination with secreted IgA. This antibody facilitates pathogen recognition and deletion prior to entrance into the body. Hence, administration via the respiratory mucosa can be favoured for all pathogens which use the respiratory tract as entry to the body, such as influenza and for all diseases directly affecting the respiratory tract such as pneumonia. Additionally, the different mucosal tissues of the human body are interconnected via the so-called “common mucosal immune system”, which allows induction of an antigen-specific immune response in distant mucosal sites. Finally, mucosal administration is also interesting in the area of therapeutic vaccination, in which a predominant cellular immune response is required, as this can efficiently be induced by this route of delivery. The review gives an introduction to respiratory vaccination, formulation approaches and application strategies.


2012 ◽  
Vol 2012 ◽  
pp. 1-29 ◽  
Author(s):  
María Ángeles Esteban

The vertebrate immune system is comprised of numerous distinct and interdependent components. Every component has its own inherent protective value, and the final combination of them is likely to be related to an animal’s immunological history and evolutionary development. Vertebrate immune system consists of both systemic and mucosal immune compartments, but it is the mucosal immune system which protects the body from the first encounter of pathogens. According to anatomical location, the mucosa-associated lymphoid tissue, in teleost fish is subdivided into gut-, skin-, and gill-associated lymphoid tissue and most available studies focus on gut. The purpose of this paper is to summarise the current knowledge of the immunological defences present in skin mucosa as a very important part of the fish immune system, serving as an anatomical and physiological barrier against external hazards. Interest in defence mechanism of fish arises from a need to develop health management tools to support a growing finfish aquaculture industry, while at the same time addressing questions concerning origins and evolution of immunity in vertebrates. Increased knowledge of fish mucosal immune system will facilitate the development of novel vaccination strategies in fish.


Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 934-944 ◽  
Author(s):  
A Hanninen ◽  
M Salmi ◽  
O Simell ◽  
D Andrew ◽  
S Jalkanen

Abstract The beta 7-integrin subunit can pair with two alpha-chains, alpha 4 and alpha E, and is expressed mainly on lymphocytes. As an alpha 4- heterodimer it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing receptor. As an alpha E-heterodimer it binds to E- cadherin and is mainly found on intestinal intraepithelial lymphocytes. Consequently, beta 7 is mostly expressed on lymphocytes of the mucosal immune system. To study the compartmentalization of these cells further we compared the distribution of such lymphocytes in two strains of mice (BALB/c and NOD) and found that the distribution of beta 7-positive lymphocytes among various lymphoid tissues in these strains was very different. In NOD mice a conspicuous population of beta 7- integrin(high) lymphocytes expressing either alpha 4, alpha E, or both, was found in nonmucosal lymphoid tissues such as peripheral lymph nodes (PLNs). They mostly expressed the PLN homing receptor L-selectin, and included both naive and memory cells on the basis of their expression of CD44/pgp-1 and CD45RB, as did the few beta 7(high) lymphocytes in BALB/c PLNs. Their homing to Peyer's patches (PPs) and PLNs was equally effective and the cells homing to PPs and PLNs were equal in their level of L-selectin and alpha 4/beta 7 expression. However, functional studies indicated that their homing to PPs mostly depended on alpha 4/beta 7-integrin, whereas they mainly used L-selectin to home to PLNs. beta 7(high) lymphocytes were found also in circulating blood of unmanipulated NOD mice, and their L-selectin expression was higher than in BALB/c mice. These results show that lymphocytes of the mucosal immune system may also express the peripheral node homing receptor L- selectin during their recirculation and that in NOD mice they frequently retain a dual homing specificity, which leads to their accumulation in nonmucosal tissues.


2020 ◽  
pp. 14-20
Author(s):  
O.A. Gizinger

Impaired functioning of the immune system against the background of viral and bacterial diseases contributes to the generalization of inflammatory processes, the development of complications, and asthenia. Immunomax is the recommended preparation for correcting immune disorders. The active ingredient is Acid Peptidoglycan from Potato Sprouts with a molecular weight of 1000-40,000 kD; Registration number: P N001919 / 02. Immunomax® stimulates the expression of genes of signaling receptors of immunity, which increases their sensitivity of immunocytes to pathogens of different nature and causes an adequate immune response in the body in the presence of the pathogen.


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