Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

2017 ◽  
Vol 38 (04) ◽  
pp. 404-416 ◽  
Author(s):  
Marcel Veltkamp ◽  
Bob Meek ◽  
David Moller ◽  
Els Beijer
Keyword(s):  
Immune System ◽  
Complex Disease ◽  
Systemic Disease ◽  
Adaptive Immune System ◽  
Unknown Etiology ◽  
Disease Pathogenesis ◽  
Amyloid A ◽  
Adaptive Immune ◽  
Etiologic Agents ◽  
Noncaseating Granulomas

AbstractSarcoidosis is a disorder of unknown etiology. It is a systemic disease, frequently involving the lungs, skin, eyes, and lymph nodes. It is characterized by formation of noncaseating granulomas at the site(s) of disease. Sarcoidosis has a complex disease pathogenesis, with involvement of both the innate and adaptive immune systems. Several innate immune system receptors including NOD-like receptors and Toll-like receptors appear to be involved in the development of sarcoidosis as well as cellular players such as dendritic cells and macrophages. Furthermore, lymphocytes from the adaptive immune system including Th1, Th17, regulatory T cells, and B cells are likely to play a role in the sarcoidosis disease pathogenesis as well. Possibly, genetic susceptibility and exposure to particular etiologic agents including mycobacterial and propionibacterial antigens, metals, and silica can cause sarcoidosis. Besides exogenous triggers, also self-compounds such as serum amyloid A and vimentin, have been found to play a role in the development of sarcoidosis. It is likely that sarcoidosis does not have one single cause but rather is the result of the interplay between different etiologic agents and the immune system in predisposed individuals.

P1-158: The Adaptive Immune System Critically Regulates Alzheimer’s Disease Pathogenesis by Modulating Microglial Function

2016 ◽  
Vol 12 ◽  
pp. P463-P464
Author(s):  
Samuel E. Marsh ◽  
Alborz Karimzadeh ◽  
Edsel M. Abud ◽  
Anita Lakatos ◽  
Stephen T. Yeung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Adaptive Immune System ◽  
Disease Pathogenesis ◽  
Adaptive Immune

scholarly journals Clinical Presentations, Pathogenesis, and Therapy of Sarcoidosis: State of the Art

2020 ◽  
Vol 9 (8) ◽  
pp. 2363
Author(s):  
Francesca Polverino ◽  
Elisabetta Balestro ◽  
Paolo Spagnolo
Keyword(s):  
Clinical Course ◽  
State Of The Art ◽  
Systemic Disease ◽  
Unknown Etiology ◽  
Therapeutic Approaches ◽  
Epidemiologic Factors ◽  
Adaptive Immune ◽  
Clinical Presentations ◽  
Specific Organ ◽  
Noncaseating Granulomas

Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of noncaseating granulomas that can occur in any organ, most commonly the lungs. Early and accurate diagnosis of sarcoidosis remains challenging because initial presentations may vary, many patients are asymptomatic, and there is no single reliable diagnostic test. Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement. From a pathobiological standpoint, sarcoidosis represents an immune paradox, where an excessive spread of both the innate and the adaptive immune arms of the immune system is accompanied by a state of partial immune anergy. For all these reasons, the optimal treatment for sarcoidosis remains unclear, with corticosteroid therapy being the current gold standard for those patients with significantly symptomatic or progressive pulmonary disease or serious extrapulmonary disease. This review is a state of the art of clinical presentations and immunological features of sarcoidosis, and the current therapeutic approaches used to treat the disease.

scholarly journals Immune Alterations in IgE and Non IgE-Associated Atopic Dermatitis

2014 ◽  
Vol 8 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Giampaolo Ricci ◽  
Elisabetta Calamelli ◽  
Francesca Cipriani
Keyword(s):  
Atopic Dermatitis ◽  
Immune System ◽  
Complex Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Skin Barrier ◽  
Underlying Mechanism ◽  
Adaptive Immune ◽  
New Findings ◽  
Immune Alterations

Atopic dermatitis is a complex disease in which a strong interaction between alterations of skin barrier and the adaptive immune system coexists. In the recent years, new findings have underlined the importance of skin proteins, especially filaggrin, which participate to the outmost layers of the skin. To strengthen this physical barrier, many factors are available, such as antimicrobial peptides, chemokines and cytokines produced by keratinocytes. Skin disruption can easily allow the allergen penetration and the local keratinocytes can promote the adaptive immune response toward a Th2 phenotype. On the other side, allergic Th2 cytokines may downregulate the production of skin barrier proteins, facilitating the penetration of allergens. Moreover, data on murine models show the absolute relevance of the systemic immune system to develop clinical skin reaction. Since the clinical aspect of patients with AD does not show different patterns whatever is the prevalent underlying mechanism, in clinical practice it is difficult to translate the different endotypes beside the IgE and non IgE associated forms. The aim of this review is to point out to the most recent knowledge in this field, which makes AD more difficult to frame in a unique clinical entity.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune

scholarly journals Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System

2021 ◽  
Vol 8 (8) ◽  
pp. 2004979
Author(s):  
Jun‐Young Park ◽  
Sung Jean Park ◽  
Jun Young Park ◽  
Sang‐Hyun Kim ◽  
Song Kwon ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Protein Corona ◽  
Unfolded Protein ◽  
Adaptive Immune

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

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