scholarly journals Food allergy in children: Part I: Pathogenesis and diagnostic approach

2003 ◽  
Vol 56 (1-2) ◽  
pp. 54-57 ◽  
Author(s):  
Jelena Tomic ◽  
Mirjana Jovanovic ◽  
Dusan Tomic
Keyword(s):  
T Cells ◽  
Food Allergy ◽  
Gastrointestinal Tract ◽  
Oral Tolerance ◽  
Food Allergies ◽  
Th2 Response ◽  
Basic Part ◽  
Immunological Mechanisms

Introduction Food allergy is a form of adverse food reaction to different nutritive agents caused by immunological mechanisms. This condition is frequent in individuals with genetic predisposition. Frequency of food allergies in childhood varies in general population from 0.3 - 7.5 %. Characteristics of neonatal and infant gastrointestinal tracts are described as well as the role of gastrointestinal tract?s immunological immaturity in development of food sensitivity. Pathogenesis Features of physical and immunological barriers of gastrointestinal tract are described as well as their role in physiological conditions, in digestion and absorption of foreign proteins and prevention of foreign agents penetration and potentially dangerous proteins into the systemic circulation. Gastrointestinal-associated lymphoid tissue (GALT) is the basic part of immunological barrier. Its first role is to induce oral tolerance. In normal conditions cytokines induce T cells towards Th2 response and also promote synthesis of IgA antibodies Pathogenic mechanisms in evolution of reaginic hypersensibility in cases of chronic inflammation are also described. Pathological status of gamma/delta T cells plays an important role in this process, resulting in loss of oral tolerance and development of sensibilitivity. Conclusion Diagnostic procedures are multiple and complex. They consist of detailed history taking clinical findings, in vitro and in vivo tests, endoscopy, elimination diets and oral provocation tests. Food allergy in childhood is often transient and resolves spontaneously.

scholarly journals A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Leticia Martin-Cruz ◽  
Carmen Sevilla-Ortega ◽  
Cristina Benito-Villalvilla ◽  
Carmen M. Diez‐Rivero ◽  
Silvia Sanchez-Ramón ◽  
...  
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Genitourinary Tract ◽  
Vaccine Formulation ◽  
Trained Immunity ◽  
Immunological Mechanisms ◽  
Tract Infections

Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ– and IL-17A–producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.

Future Approaches to Food Allergy

PEDIATRICS ◽  
2003 ◽  
Vol 111 (Supplement_3) ◽  
pp. 1672-1680
Author(s):  
Anna Nowak-Wegrzyn
Keyword(s):  
Food Allergy ◽  
Immunoglobulin E ◽  
Fatal Outcome ◽  
Diagnostic Methods ◽  
Food Allergies ◽  
In Vitro Assays ◽  
Activation Markers ◽  
Treatment Of Food Allergy

Food allergy affects ∼2% of the general US population, and its prevalence seems to be increasing. Despite the potential for a fatal outcome, no definitive therapies are available for food allergy. This article reviews novel approaches for the diagnosis and treatment of food allergy. Improved diagnostic methods include more precise in vitro and in vivo tests for immunoglobulin E-mediated food allergies, in vitro assays for predicting development of oral tolerance, and novel noninvasive tests for cell-mediated food allergies such as patch testing, cytokine assays, and detection of eosinophil activation markers. Several promising novel immunomodulatory approaches to food allergy are discussed, including monoclonal anti-immunoglobulin E; probiotics; traditional Chinese medicine; and immunotherapy with modified food proteins, peptides, bacterial adjuvants, and immunostimulatory sequences.

Food Allergy—Practical Solutions for a Common Problem

1995 ◽  
Vol 112 (5) ◽  
pp. P37-P37
Author(s):  
Alan B. McDaniel ◽  
Edwyn I. Boyd
Keyword(s):  
Food Allergy ◽  
Food Allergies ◽  
In Vitro Tests ◽  
Dietary Manipulation ◽  
Educational Objectives ◽  
Specific Therapy ◽  
Clinical Presentations ◽  
Specific Food

Educational objectives: To recognize characteristic clinical presentations of patients with food allergy, to understand concepts of fixed and “cyclic” allergy, and to treat specific food allergies using in-vivo and in-vitro tests, dietary manipulation, and antigen-specific therapy.

scholarly journals Low Dose Leishmania major Promotes a Transient T Helper Cell Type 2 Response That Is Down-regulated by Interferon γ–producing CD8+ T Cells

2004 ◽  
Vol 199 (11) ◽  
pp. 1559-1566 ◽  
Author(s):  
Jude E. Uzonna ◽  
Karen L. Joyce ◽  
Phillip Scott
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Low Dose ◽  
Leishmania Major ◽  
Interferon Γ ◽  
Th2 Response ◽  
Th1 Response ◽  
Th Cell

An unresolved issue in the field of T helper (Th) cell development relates to the findings that low doses of antigen promote Th2 cell development in vitro, whereas several classic in vivo studies suggest the opposite. Here we resolve this paradox by studying the early immune response in mice after infection with different doses of Leishmania major. We found that low parasite doses induced a Th2 response in C57BL/6 (B6) mice, whereas high doses induced a Th1 response. However, the Th2 response in low dose–infected mice was transient and the animals healed. The appearance of a Th1 response after low dose infection was dependent upon the concomitant activation of interferon γ–producing CD8+ T cells. In the absence of CD8+ T cells, the Th2 response was maintained. However, either neutralization of interleukin (IL)-4 or administration of IL-12 promoted a Th1 response after low dose infection of CD8-deficient mice, indicating that the required role for CD8+ T cells was limited to modulation of CD4+ T cell responses. Thus, the discrepant results seen between in vivo and in vitro studies on the effects of antigen dose on Th cell differentiation may depend upon whether CD8+ T cells participate in the immune response.

Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 1 (2) ◽  
pp. 122-128
Author(s):  
Syuichi Koarada ◽  
Yuri Sadanaga ◽  
Natsumi Nagao ◽  
Satoko Tashiro ◽  
Rie Suematsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production

627 The DLL3-targeted half-life extended bispecific T cell engager (HLE BiTE®) immune-oncology therapy AMG 757 has potent antitumor activity in neuroendocrine cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A663-A663
Author(s):  
Keegan Cooke ◽  
Juan Estrada ◽  
Jinghui Zhan ◽  
Jonathan Werner ◽  
Fei Lee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Mouse Models ◽  
T Cell Activation ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Human T Cells

BackgroundNeuroendocrine tumors (NET), including small cell lung cancer (SCLC), have poor prognosis and limited therapeutic options. AMG 757 is an HLE BiTE® immune therapy designed to redirect T cell cytotoxicity to NET cells by binding to Delta-like ligand 3 (DLL3) expressed on the tumor cell surface and CD3 on T cells.MethodsWe evaluated activity of AMG 757 in NET cells in vitro and in mouse models of neuroendocrine cancer in vivo. In vitro, co-cultures of NET cells and human T cells were treated with AMG 757 in a concentration range and T cell activation, cytokine production, and tumor cell killing were assessed. In vivo, AMG 757 antitumor efficacy was evaluated in xenograft NET and in orthotopic models designed to mimic primary and metastatic SCLC lesions. NSG mice bearing established NET were administered human T cells and then treated once weekly with AMG 757 or control HLE BiTE molecule; tumor growth inhibition was assessed. Pharmacodynamic effects of AMG 757 in tumors were also evaluated in SCLC models following a single administration of human T cells and AMG 757 or control HLE BiTE molecule.ResultsAMG 757 induced T cell activation, cytokine production, and potent T cell redirected killing of DLL3-expressing SCLC, neuroendocrine prostate cancer, and other DLL3-expressing NET cell lines in vitro. AMG 757-mediated redirected lysis was specific for DLL3-expressing cells. In patient-derived xenograft and orthotopic models of SCLC, single-dose AMG 757 effectively engaged human T cells administered systemically, leading to a significant increase in the number of human CD4+ and CD8+ T cells in primary and metastatic tumor lesions. Weekly administration of AMG 757 induced significant tumor growth inhibition of SCLC (figure 1) and other NET, including complete regression of established tumors and clearance of metastatic lesions. These findings warranted evaluation of AMG 757 (NCT03319940); the phase 1 study includes dose exploration (monotherapy and in combination with pembrolizumab) and dose expansion (monotherapy) in patients with SCLC (figure 2). A study of AMG 757 in patients with neuroendocrine prostate cancer is under development based on emerging data from the ongoing phase 1 study.Abstract 627 Figure 1AMG 757 Significantly reduced tumor growth in orthotopic SCLC mouse modelsAbstract 627 Figure 2AMG 757 Phase 1 study designConclusionsAMG 757 engages and activates T cells to kill DLL3-expressing SCLC and other NET cells in vitro and induces significant antitumor activity against established xenograft tumors in mouse models. These preclinical data support evaluation of AMG 757 in clinical studies of patients with NET.Ethics ApprovalAll in vivo work was conducted under IACUC-approved protocol #2009-00046.

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