P6047 Expression of TLR2 pattern recognition receptor on mononuclear cells cultured with ligands among cattle ranked by estimated breeding values for adaptive immune response traits

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

Download Full-text

Adaptive immunity

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.050103 ◽

2010 ◽

pp. 224-234

Author(s):

Paul Klenerman

Keyword(s):

Infectious Disease ◽

Immune Response ◽

Pattern Recognition ◽

Adaptive Immunity ◽

Adaptive Response ◽

Critical Role ◽

Adaptive Immune Response ◽

Structural Features ◽

Adaptive Immune ◽

Single Organism

Following the innate immune response, which acts very rapidly, the adaptive immune response plays a critical role in host defence against infectious disease. Unlike the innate response, which is triggered by pattern recognition of pathogens, i.e. features that are common to many bacteria or viruses, the adaptive response is triggered by structural features—known as antigens or epitopes—that are typically unique to a single organism....

Download Full-text

Time-Resolved Gene Expression Analysis Monitors the Regulation of Inflammatory Mediators and Attenuation of Adaptive Immune Response by Vitamin D

International Journal of Molecular Sciences ◽

10.3390/ijms23020911 ◽

2022 ◽

Vol 23 (2) ◽

pp. 911

Author(s):

Andrea Hanel ◽

Carsten Carlberg

Keyword(s):

Gene Expression ◽

Vitamin D ◽

Immune Response ◽

Immune System ◽

Calcium Binding ◽

Target Genes ◽

Mononuclear Cells ◽

Adaptive Immune Response ◽

Time Resolved ◽

Adaptive Immune

Peripheral blood mononuclear cells (PBMCs) belong to the innate and adaptive immune system and are highly sensitive and responsive to changes in their systemic environment. In this study, we focused on the time course of transcriptional changes in freshly isolated human PBMCs 4, 8, 24 and 48 h after onset of stimulation with the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Taking all four time points together, 662 target genes were identified and segregated either by time of differential gene expression into 179 primary and 483 secondary targets or by driver of expression change into 293 direct and 369 indirect targets. The latter classification revealed that more than 50% of target genes were primarily driven by the cells' response to ex vivo exposure than by the nuclear hormone and largely explained its down-regulatory effect. Functional analysis indicated vitamin D’s role in the suppression of the inflammatory and adaptive immune response by down-regulating ten major histocompatibility complex class II genes, five alarmins of the S100 calcium binding protein A family and by affecting six chemokines of the C-X-C motif ligand family. Taken together, studying time-resolved responses allows to better contextualize the effects of vitamin D on the immune system.

Download Full-text

Immune defects in patients with pulmonary Mycobacterium abscessus disease without cystic fibrosis

ERJ Open Research ◽

10.1183/23120541.00590-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00590-2020

Author(s):

Milou M.F. Schuurbiers ◽

Mariolina Bruno ◽

Sanne M.H. Zweijpfenning ◽

Cecile Magis-Escurra ◽

Martin Boeree ◽

...

Keyword(s):

Cystic Fibrosis ◽

Immune Response ◽

Pulmonary Disease ◽

Mononuclear Cells ◽

Interleukin 1 ◽

Adaptive Immune Response ◽

Mycobacterium Abscessus ◽

Adaptive Immune ◽

Ifn Γ ◽

Immune Defects

The prevalence of Mycobacterium abscessus infections in non-cystic fibrosis (CF) patients has increased in recent years. In this study, we investigate whether immune defects explain the apparent susceptibility to this opportunistic infection in non-CF patients.We performed stimulations of peripheral blood mononuclear cells and whole blood from 13 patients with M. abscessus pulmonary disease and 13 healthy controls to investigate their cytokine production after 24 h and 7 days.Patients were predominantly women (54%) with a mean age of 59 years; 62% had nodular bronchiectatic disease. Many patients had predisposing pulmonary diseases, such as COPD (46%), and asthma (23%). Patients with COPD showed an impaired interleukin (IL)-6 response to M. abscessus and a reduced IL-17 response to Candida, together with a M. abscessus-specific enhanced IL-22 production. Patients without COPD showed higher levels of interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory molecule. Within the non-COPD patients, those with bronchiectasis showed defective interferon (IFN)-γ production in response to Candida albicans.In conclusion, susceptibility to M. abscessus is likely determined by a combination of immunological defects and predisposing pulmonary disease. The main defect in the innate immune response was a shift of the ratio of IL-1β to IL-1Ra, which decreased the bioactivity of this pathway in the adaptive immune response. In the adaptive immune response there was defective IL-17 and IFN-γ production. Patients with COPD and bronchiectasis showed different cytokine defects. It is therefore crucial to interpret the immunological results within the clinical background of the patients tested.

Download Full-text

Vitamin D in Early Childhood and the Effect on Immunity toMycobacterium tuberculosis

Clinical and Developmental Immunology ◽

10.1155/2012/430972 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 24

Author(s):

Anna Jane Battersby ◽

Beate Kampmann ◽

Sarah Burl

Keyword(s):

Vitamin D ◽

Immune Response ◽

Pattern Recognition ◽

Early Childhood ◽

Potential Role ◽

Adaptive Immune Response ◽

Adaptive Immune ◽

Increased Susceptibility ◽

Stimulation Of

A potential role for vitamin D as a therapeutic immunomodulator in tuberculosis (TB) has been recognised for over 150 years, but has only recently returned to the centre of the research arena due to the increasing awareness of the global vitamin D deficiency epidemic. As early as birth a child is often deficient in vitamin D, which may not only affect their bone metabolism but also modulate their immune function, contributing to the increased susceptibility to many infections seen early in life. Recent studies have begun to explain the mechanisms by which vitamin D affects immunity. Antimicrobial peptides are induced in conjunction with stimulation of innate pattern recognition receptors enhancing immunity to particular infections. In contrast the role of vitamin D within the adaptive immune response appears to be more regulatory in function, perhaps as a mechanism to reduce unwanted inflammation. In this paper we focus on the effect of vitamin D on immunity to TB. Where much of the attention has been paid by past reviews to the role of vitamin D in adult TB patients, this paper, where possible, focuses on research in paediatric populations.

Download Full-text