scholarly journals Development of Mucosal Immunity in Children: A Rationale for Sublingual Immunotherapy?

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Aleksandra Szczawinska-Poplonyk

The mucosal immune system has bidirectional tasks to mount an effective defense against invading harmful pathogens and to suppress the immune response to alimentary antigens and commensal bacterial flora. Oral tolerance is a suppression of the mucosal immune pathway related to a specific immunophenotype of the dendritic cells and an induction of the regulatory T cells as well as with the silencing of the effector T cell response by anergy and deletion. The physiological dynamic process of the anatomical and functional maturation of the immune system occurring in children during pre- and postnatal periods is a significant factor, having an impact on the fine balance between the activation and the suppression of the immune response. In this paper, mechanisms of mucosal immunity and tolerance induction in terms of maturational issues are discussed with a special emphasis on the implications for a novel therapeutic intervention in allergic diseases via the sublingual route.

2013 ◽  
Vol 109 (S2) ◽  
pp. S3-S11 ◽  
Author(s):  
Patricia Castro-Sánchez ◽  
José M. Martín-Villa

Gut mucosal surfaces separate the external environment from the internal sterile environment and so represent a first line of defence system. This barrier faces environments rich in pathogens that have developed effective mechanisms for colonisation of epithelial surfaces and invasion of mucosal tissues, but also harmless antigens such as food, airborne antigens or commensal bacterial flora. The latter represent the vast majority of the encountered antigens and require an appropriate response characterised by either ignorance or active suppression. However, for the former, a robust immune response is needed. Mucosae have developed a complex immune system that is capable of mounting an immune response against pathogenic antigens, while maintaining the required ignorance or active suppression against non-pathogenic antigens. Taking advantage of this knowledge, strategies have been devised to induce oral tolerance to antigens involved in experimental autoimmune disease or human conditions. It is now known that oral tolerance induces the up-regulation and activation of T cells with regulatory properties, a subtype of CD4+ T cells whose function is to regulate functions of other T lymphocytes to avoid excessive immune activation. Amongst them, the Th3 cells (cells that express the latency-associated peptide on the surface and secrete transforming growth factor β, a cytokine with immunoregulatory properties) are especially relevant in the induction of oral tolerance. Orally fed antigens seek to generate these types of cells in the treatment of autoimmune diseases in experimental animals or human subjects.


2002 ◽  
Vol 88 (6) ◽  
pp. 671-680 ◽  
Author(s):  
Tanja M. R. Kjær ◽  
Hanne Frøkiær

We investigated the effect of feeding extracts of four different legumes (red kidney bean (Phaseolus vulgaris), peanut (Arachis hypogaea), soyabean (Glycine max) and pea (Pisum sativum) on the specific immune response against a food protein. Mice were fed ovomucoid and the specific immune response was evaluated. Ovomucoid fed alone resulted in oral tolerance induction measured as both a reduced ovomucoid-specific spleen cell proliferation and antibody response. Feeding kidney-bean extract prevented induction of oral tolerance to ovomucoid measured as spleen cell proliferation in vitro. Pure kidney-bean lectin also prevented oral tolerance induction, suggesting that lectin in the kidney-bean extract caused inhibition of oral tolerance. Parenteral administration (intravenous and intraperitoneal) of pure kidney-bean lectin had no significant influence on oral tolerance induction. Soyabean extract also influenced the immune response against ovomucoid; however, this was not as pronounced as for kidney bean and was only significant (P<0·001) for the antibody response. No effect was observed when pea extract was fed and peanut extract had a non-significant effect on induction of oral tolerance and on the general immune response. Plasma antibodies against kidney-bean lectin, but not against the three other legume lectins, were detected. Our current findings show that other dietary components can influence the specific immune response against food proteins. Various dietary components may thus contribute to the onset of adverse immunological responses.


2020 ◽  
Vol 21 (2) ◽  
pp. 541 ◽  
Author(s):  
Arnold J. Levine

The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.


2001 ◽  
Vol 75 (10) ◽  
pp. 4699-4704 ◽  
Author(s):  
Nicole Kruse ◽  
Olaf Weber

ABSTRACT Viruses have evolved numerous mechanisms to avoid host immune reactions. Here we report a mechanism by which Parapoxvirus ovis (PPVO) interferes with antigen presentation. PPVO (orf virus) causes orf, an acute skin disease of sheep and goats worldwide. Importantly, PPVO can repeatedly infect its host in spite of a vigorous inflammatory and host immune response to the infection. We demonstrate in a mouse system that PPVO induces apoptosis in a significant number of antigen-presenting cells after intraperitoneal injection using the CD95 pathway, thus preventing a primary T-cell response. We also show that PPVO induces a compensatory activation of the immune system. Our results may help to explain the phenomenon that natural PPVO infections in sheep occur repeatedly even after short intervals. They also suggest that the combination of immunosuppressive and immunostimulatory mechanisms is an effective survival strategy that might be used in other viruses as well.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2141
Author(s):  
Katie Alexander ◽  
Charles O. Elson

Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.


Author(s):  
Assia Eljaafari ◽  
Pierre Miossec

The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.


Author(s):  
Marina V. Fedoseenko ◽  
Veronika A. Petrova ◽  
Leyla S. Namazova-Baranova

Background. T-cell response is shifted towards Th2-type predominance in newborns. This makes them particularly vulnerable to exposure of various external pathogens, development of severe infections, moreover, it is also a risk factor for allergic diseases development. Various methods of switching the immune response to Th1-type are currently under research, and one of them is vaccination.Objective. The aim of the study is to provide data on the prevalence of allergic pathology among children vaccinated against tuberculosis and hepatitis B, as well as the effect of vaccines on immune response type.Results. Data on both increase and decrease in the prevalence of atopic conditions in children vaccinated with BCG and against hepatitis B were analyzed, thus, most of them cannot be considered reliable. The results of several large studies do not reveal any correlation between vaccination and the presence of allergic disease in children. There is data that BCG and hepatitis B vaccines shift the immune response towards Th1-type activation.Conclusion. Vaccination in the early neonatal period may affect switching of the immune response towards Th1-type. That, in turn, can affect the prevalence of allergic pathology in vaccinated children. However, the data available for now is not sufficient to reliably estimate the possible effect of vaccination on atopic conditions manifestation in the future.


Author(s):  
Natália Pinheiro-Rosa ◽  
Lícia Torres ◽  
Mariana de Almeida Oliveira ◽  
Marcos Felipe Andrade de Oliveira ◽  
Mauro Andrade de Freitas Guimaraes ◽  
...  

Abstract Oral tolerance is a physiological phenomenon described more than a century ago as a suppressive immune response to antigens that gain access to the body by the oral route. It is a robust and long-lasting event with local and systemic effects in which the generation of mucosally-induced regulatory T cells (iTreg) play an essential role. The idea of using oral tolerance to inhibit autoimmune and allergic diseases by oral administration of target antigens was an important development that was successfully tested in 1980’s. Since then, several studies have shown that feeding specific antigens can be used to prevent and control chronic inflammatory diseases in both animal models and clinically. Therefore, oral tolerance can be classified as an antigen-specific form of oral immunotherapy (OIT). In the light of novel findings on mechanisms, sites of induction and factors affecting oral tolerance, this review will focus on specific characteristics of oral tolerance induction and how they impact in its therapeutic application.


2020 ◽  
Vol 36 (1) ◽  
pp. 511-528
Author(s):  
Kirsty Logan ◽  
George Du Toit ◽  
Mattia Giovannini ◽  
Victor Turcanu ◽  
Gideon Lack

Pediatric allergic disease is a significant health concern worldwide, and the prevalence of childhood eczema, asthma, allergic rhinitis, and food allergy continues to increase. Evidence to support specific interventions for the prevention of eczema, asthma, and allergic rhinitis is limited, and no consensus on prevention strategies has been reached. Randomized controlled trials investigating the prevention of food allergy via oral tolerance induction and the early introduction of allergenic foods have been successful in reducing peanut and egg allergy prevalence. Infant weaning guidelines in the United Sates were recently amended to actively encourage the introduction of peanut for prevention of peanut allergy.


2006 ◽  
Vol 203 (3) ◽  
pp. 519-527 ◽  
Author(s):  
Tim Worbs ◽  
Ulrike Bode ◽  
Sheng Yan ◽  
Matthias W. Hoffmann ◽  
Gabriele Hintzen ◽  
...  

Oral tolerance induction is a key feature of intestinal immunity, generating systemic nonresponsiveness to ingested antigens. In this study, we report that orally applied soluble antigens are exclusively recognized in the intestinal immune system, particularly in the mesenteric lymph nodes. Consequently, the initiation of oral tolerance is impeded by mesenteric lymphadenectomy. Small bowel transplantation reveals that mesenteric lymph nodes require afferent lymph to accomplish the recognition of orally applied antigens. Finally, oral tolerance cannot be induced in CCR7-deficient mice that display impaired migration of dendritic cells from the intestine to the mesenteric lymph nodes, suggesting that immunologically relevant antigen is transported in a cell-bound fashion. These results demonstrate that antigen transport via afferent lymphatics into the draining mesenteric lymph nodes is obligatory for oral tolerance induction, inspiring new therapeutic strategies to exploit oral tolerance induction for the prevention and treatment of autoimmune diseases.


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