[The Role of Adoptive Transfer of Immune Cells in Helminth- induced Regulation of Allergy and Autoimmune Diseases].
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Abstract:
Parasitic worms (helminth) or their derivates can inhibit allergy and autoimmune diseases by inducing the activation of immune cells and thus the release of regulatory factors. A large number of animal experiments have shown that adoptive transfer of lymphocytes can protect against immune deregulation and have potential clinical applications. In this review, we discuss the research progress on the role of adoptive transfer of immune cells in worm-induced regulation of allergy and autoimmune diseases.Keywords:
Adoptive Cell Transfer
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Parasitic
helminths modulate host immune responses. While the induction of type 2 immune
responses is a widely recognized feature of helminth infections, a network of
regulatory immune responses is often dominant during the chronic phase of
infection. Suppression of the host immune system during helminth infections
inhibits anti-parasite immunity, prevents tissue damage due to excessive
inflammation and conveys spill-over suppression to inflammatory conditions such
as allergy and asthma. The first part of this thesis focuses on the role of
regulatory B cells, a prominent member of the immune regulatory network, in
protection from allergic asthma by chronic Schistosoma (S.) mansoni infections.
It furthermore identifies signals required for schistosome-induced regulatory B
cell development. The second part of this thesis describes the protective
effect of S. mansoni eggs, and a specific egg-derived glycoprotein, against
allergic asthma in the absence of chronic infection. A better understanding how
helminthes including S. mansoni modulate host immune responses, and the
implications this has for inflammatory diseases such as allergic asthma, may
provide valuable leads for the development of novel pharmaceutical agents for
the treatment of allergic disorders.
Regulatory T cell
Allergic Inflammation
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Although various mechanisms involving antibodies and various cell types participate, a Thl and Th2 cells imbalance seems to play a central role for allergy development. Other lymphocyte subpopulations, such as Th17, CD4 FOXP3, and Th9 positive regulatory T lymphocytes may also be involved in the allergic response. Regulatory processes are an appealing target for therapeutic approaches aiming to solve allergic reactions by restoring the delicate balance within the immune system. Transfer factor (TF) or dialyzable leukocyte extract is meant to transfer cell-mediated immunity from immune competent donors to unsensitized or deficient recipients. A PubMed search on the current knowledge on TF indicates that TF may restore the Th1/Th2 balance and improve immune regulatory mechanisms of patients receiving it. Our preliminary results demonstrate that TF induces mRNA expression of IFN-g, osteopontin, RANTES, and hBD-2 in human healthy subjects. TF has been used to treat a variety of immune dysfunction related-pathologies, such as allergy, autoimmunity, immunodeficiencies, infectious diseases and tumors. Patients receiving TF together with their conventional treatment often have better clinical evolution than without it, as we have witnessed, adding TF to the usual medical treatment of allergic diseases as an attempt to provide allergic patients with those regulatory elements that they apparently lack but require to achieve properly regulated immune responses and thus obtain a faster and better resolution of allergic reactions.
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Flora
Glory
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Natural selection should favor the transfer of immune competence from one generation to the next in a context-dependent manner. Transgenerational immune priming (TGIP) is expected to evolve when species exploit pathogen-rich environments and exhibit extended overlap of parent–offspring generations. Dampwood termites are hemimetabolous, eusocial insects (Blattodea: Archeotermopsidae) that possess both of these traits. We predict that offspring of pathogen-exposed queens of Zootermopsis angusticollis will show evidence of a primed immune system relative to the offspring of unexposed controls. We found that Relish transcripts, one of two immune marker loci tested, were enhanced in two-day-old embryos when laid by Serratia-injected queens. These data implicate the immune deficiency (IMD) signaling pathway in TGIP. Although an independent antibacterial assay revealed that embryos do express antibacterial properties, these do not vary as a function of parental treatment. Taken together, Z. angusticollis shows transcriptional but not translational evidence for TGIP. This apparent incongruence between the transcriptional and antimicrobial response from termites suggests that effectors are either absent in two-day-old embryos or their activity is too subtle to detect with our antibacterial assay. In total, we provide the first suggestive evidence of transgenerational immune priming in a termite.
Eusociality
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The immune system is composed of a complex network of different cell types protecting the body against various possible threats. Among these cells are T-helper (Th) cells type 1 (Th1) and type 2 (Th2), as well as T regulatory (Treg) cells. Th1 and Th2 are supposed to be in balance with each other, while Tregs regulate the immune response, by halting it when the desired effect, i.e. destroying the threat, is acquired. However, sometimes this intricate interplay in the immune system is disturbed, leading to diseases as type 1 diabetes (T1D), celiac disease or allergic disease. According to the paradigm claiming that Th1- and Th2-cells inhibit each other a coexistence of a Th1-deviated disease and a Th2-deviated disease seems unlikely. This thesis aimed to examine the immune response with focus on subsets of T-cells in children with T1D, celiac disease, allergy, or a combination of two of these diseases, in comparison to reference children (healthy). In line with previous findings we observed that children with celiac disease showed a decreased spontaneous Th2-associated secretion, whereas children with allergic disease showed increased birch- and cat-induced Th2-associated response. The most remarkable results in this thesis are those observed in children with combinations of diseases. The combination of T1D and celiac disease decreased the Th1-associated response against several antigens, but instead displayed a more pronounced Treg-associated response. Further, in children with combined T1D and allergy an increased Th1- and Th2-associated response was seen to a general stimulus, and an increased birch-induced Th1-, Th2-, Treg- and pro-inflammatory response. In contrast, the combination of allergy and celiac disease showed a decreased spontaneous Th1-, Th2-, Treg- and pro-inflammatory response. In conclusion, we observed that two Th1-deviated diseases in combination suppress the immune response and increase the regulatory activity. Further it seems that allergy has the ability to shift the immune response in diverging directions depending on which disease it is combined with. The observed suppressive effect might be due to exhaustion of the immune system from the massive pressure of two immunological diseases in combination, while the pronounced Treg response might be caused by an attempt to compensate for the dysfunction. These results shed some light on the intriguing and challenging network that constitutes the immune system, and hopefully give clues regarding disease prevention and treatment.
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Parasitic worms (helminth) or their derivates can inhibit allergy and autoimmune diseases by inducing the activation of immune cells and thus the release of regulatory factors. A large number of animal experiments have shown that adoptive transfer of lymphocytes can protect against immune deregulation and have potential clinical applications. In this review, we discuss the research progress on the role of adoptive transfer of immune cells in worm-induced regulation of allergy and autoimmune diseases.
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Abstract The increased prevalence of atopic diseases, i.e. atopic eczema, allergic rhinitis and asthma, has been described as the epidemic of the 21st century in Western societies. New approaches in the fight against allergic diseases are clearly called for, the target being the persistence of the allergic responder pattern beyond infancy. The advantage afforded by elimination diets lies in the silencing of specific allergic inflammation induced by an offending food. Novel nutritional approaches, beyond the treatment of food allergies, have recently attracted research interest subsequent to the identification of the immunomodulatory potential of specific dietary compounds. Dietary lipids as immunomodulators may prevent allergic sensitization by down‐regulating inflammatory response whilst protecting the epithelial barrier. Probiotic bacteria have been shown to reinforce the different lines of gut defence: immune exclusion, immune elimination and immune regulation. On this basis, the strategy against allergic disease proposed here is based on the administration of tolerogenic gut‐processed peptide fragments of a specific protein, in addition to the use of specific dietary compounds such as fatty acids and antioxidants, and introducing a microbial stimulus for the immature immune system by means of cultures of beneficial live micro‐organisms characteristic of the healthy infant gut microbiota.
Allergic Inflammation
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