The molecular basis of immune-based platelet disorders

Abstract Platelets have a predominant role in haemostasis, the maintenance of blood volume and emerging roles as innate immune cells, in wound healing and in inflammatory responses. Platelets express receptors that are important for platelet adhesion, aggregation, participation in inflammatory responses, and for triggering degranulation and enhancing thrombin generation. They carry a cargo of granules bearing enzymes, adhesion molecules, growth factors and cytokines, and have the ability to generate reactive oxygen species. The platelet is at the frontline of a host of cellular responses to invading pathogens, injury, and infection. Perhaps because of this intrinsic responsibility of a platelet to rapidly respond to thrombotic, pathological and immunological factors as part of their infantry role; platelets are susceptible to targeted attack by the adaptive immune system. Such attacks are often transitory but result in aberrant platelet activation as well as significant loss of platelet numbers and platelet function, paradoxically leading to elevated risks of both thrombosis and bleeding. Here, we discuss the main molecular events underlying immune-based platelet disorders with specific focus on events occurring at the platelet surface leading to activation and clearance.

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The Pathology of Orthopedic Implant Failure Is Mediated by Innate Immune System Cytokines

Mediators of Inflammation ◽

10.1155/2014/185150 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 80

Author(s):

Stefan Landgraeber ◽

Marcus Jäger ◽

Joshua J. Jacobs ◽

Nadim James Hallab

Keyword(s):

Immune System ◽

Innate Immune System ◽

Science Studies ◽

Inflammatory Responses ◽

Total Joint Replacement ◽

Adaptive Immune System ◽

Receptor Activation ◽

Innate Immune ◽

Subsequent Formation ◽

Adaptive Immune

All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15–25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or “aseptic loosening” is a potentially life-threatening condition due to the serious complications in older people (>75 yrs) of total joint replacement revision surgery. In some people implant debris (particles and ions from metals) can influence the adaptive immune system as well, giving rise to the concept of metal sensitivity. However, a consensus of studies agrees that the dominant form of this response is due to innate reactivity by macrophages to implant debris where both danger (DAMP) and pathogen (PAMP) signalling elicit cytokine-based inflammatory responses. This paper discusses implant debris induced release of the cytokines and chemokines due to activation of the innate (and the adaptive) immune system and the subsequent formation of osteolysis. Different mechanisms of implant-debris reactivity related to the innate immune system are detailed, for example, danger signalling (e.g., IL-1β, IL-18, IL-33, etc.), toll-like receptor activation (e.g., IL-6, TNF-α, etc.), apoptosis (e.g., caspases 3–9), bone catabolism (e.g., TRAP5b), and hypoxia responses (Hif1-α). Cytokine-based clinical and basic science studies are in progress to provide diagnosis and therapeutic intervention strategies.

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Adipocytes, Innate Immunity and Obesity: A Mini-Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.650768 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alecia M. Blaszczak ◽

Anahita Jalilvand ◽

Willa A. Hsueh

Keyword(s):

Adipose Tissue ◽

Immune System ◽

Immune Cells ◽

Adaptive Immune System ◽

Innate Immune ◽

Lymphoid Cells ◽

Innate Immune Cells ◽

Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

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The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

10.1101/2021.05.06.442992 ◽

2021 ◽

Author(s):

Phillip Wibisono ◽

Shawndra Wibisono ◽

Jan Watteyne ◽

Chia-Hui Chen ◽

Durai Sellegounder ◽

...

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Adaptive Immune System ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Genes ◽

C Elegans ◽

Adaptive Immune ◽

Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

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Changes in immune responses to oxidized LDL epitopes during aging in hypercholesterolemic apoE(−/−) mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00511.2005 ◽

2006 ◽

Vol 291 (6) ◽

pp. R1644-R1650 ◽

Cited By ~ 4

Author(s):

Paul C. Dimayuga ◽

Xiaoning Zhao ◽

Juliana Yano ◽

Kuang-Yuh Chyu

Keyword(s):

Immune Response ◽

Immune Responses ◽

Time Course ◽

Oxidized Ldl ◽

Adaptive Immune Response ◽

Adaptive Immune System ◽

Innate Immune ◽

Collagen Content ◽

Aortic Sinus ◽

Adaptive Immune

Atherosclerosis is a disease associated with aging and is subject to modulation by both the innate and adaptive immune system. The time course of age-dependent changes in immune regulation in the context of atherosclerosis has not been characterized. This study aims to describe alteration of the immune responses to oxidized LDL (oxLDL) during aging that is associated with changes in plaque size and phenotype in apoE(−/−) mice. Mice fed a Western diet were euthanized at 15–17, 36, or >52 wk of age. The descending aortas were stained for assessment of extent of atherosclerosis. Plaque lipid, macrophage, and collagen content were evaluated in aortic sinus lesions. The adaptive immune response to oxLDL was assessed using anti-malondialdehyde-oxidized LDL (MDA-LDL) and copper-oxidized LDL (Cu-oxLDL) IgG, and the innate immune response was assessed using anti-Cu-oxLDL and phosphorylcholine (PC) IgM. Aging was associated with a significant increase in plaque area and collagen content and a decrease in plaque macrophage and lipid content. MDA-LDL IgG significantly increased at 36 wk but was reduced in mice >52 wk. Cu-oxLDL IgG increased with age and IgG-apoB immune complexes were increased in the >52 wk group. Cu-oxLDL and PC IgM significantly increased with age. The expression of splenic cytokines such as IFN-γ, IL-4, and IL-10 increased with age. Our study shows a generalized increase in innate immune responses associated with progression of atherosclerosis and a less inflammatory and less lipid-containing plaque phenotype during aging. The adaptive immune response appeared to be less generalized, with a specific reduction in MDA-LDL IgG.

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Antibody equivalent molecules of the innate immune system: parallels between innate and adaptive immune proteins

Innate Immunity ◽

10.1177/1753425910370498 ◽

2010 ◽

Vol 16 (3) ◽

pp. 131-137 ◽

Cited By ~ 19

Author(s):

Nades Palaniyar

Keyword(s):

Pattern Recognition ◽

Immune System ◽

Innate Immune System ◽

Adaptive Immune System ◽

Surfactant Protein ◽

Innate Immune ◽

Future Research ◽

Surfactant Protein D ◽

Adaptive Immune ◽

Carbohydrate Arrays

Soluble pattern-recognition innate immune proteins functionally resemble the antibodies of the adaptive immune system. Two major families of such proteins are ficolins and collectins or collagenous lectins (e.g. mannose-binding lectin [MBL], surfactant proteins [SP-A and SP-D] and conglutinin). In general, subunits of ficolins and collectins recognize the carbohydrate arrays of their targets via globular trimeric carbohydrate-recognition domains (CRDs) whereas IgG, IgM and other antibody isotypes recognize proteins via dimeric antigen-binding domains (Fab). Considering the structure and functions of these proteins, ficolins and MBL are analogous to molecules with the complement activating functions of C1q and the target recognition ability of IgG. Although the structure of SP-A is similar to MBL, it does not activate the complement system. Surfactant protein-D and conglutinin could be considered as the collagenous non-complement activating giant IgMs of the innate immune system. Proteins such as peptidoglycan-recognition proteins, pentraxins and agglutinin gp-340/DMBT1 are also pattern-recognition proteins. These proteins may be considered as different isotypes of antibody-like molecules. Proteins such as defensins, cathelicidins and lactoferrins directly or indirectly alter microbes or microbial growth. These proteins may not be considered as antibodies of the innate immune system. Hence, ficolins and collectins could be considered as specialized ‘antibodies of the innate immune system’ instead of ‘ante-antibody’ innate immune molecules. The discovery, structure, functions and future research directions of many of these soluble proteins and receptors such as Toll-like and NOD-like receptors are discussed in this special issue of Innate Immunity.

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RESPON IMUN HOSPES TERHADAP INFEKSI Vibrio cholerae

Biocelebes ◽

10.22487/bioceb.v15i2.15777 ◽

2022 ◽

Vol 15 (2) ◽

pp. 113-124

Author(s):

Musjaya, M Guli

Keyword(s):

Immune System ◽

Epithelial Cells ◽

Pathogenic Bacteria ◽

Adaptive Immune System ◽

Innate Immune ◽

Phagocytic Cells ◽

Protection Mechanism ◽

Adaptive Immune ◽

Natural Defense ◽

A Site

The immune sistem is a way of the body’s defense sistem to save the host from the invasion of outside pathogen. Based on how respon to disease, that differentiated into two immune system are innate and adaptive system. Because it an cant throgh the stomach, these pathogenic bacteria go to the small intestin as a site infection. In the intestine, V. cholerae bactesia adhere and colonize and invasion to intestinal epihelial cells. Protection mechanism to V. cholerae are the natural defense presence of tick mucosa on the surface of epithelial cells can inhibit pathogene to adhere tointestinal epithelial cells. One anothet defense namely innate immune system did by phagocytic cells to attac pathogen agent and adaptive immune system involves IgA to opsonization so that can increase intestinal mucosal immune system

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Impact of Microorganisms and Parasites on Neuronally Controlled Drosophila Behaviours

Cells ◽

10.3390/cells10092350 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2350

Author(s):

Martina Montanari ◽

Julien Royet

Keyword(s):

Immune System ◽

Animal Behavior ◽

Innate Immune System ◽

Adaptive Immune System ◽

Model System ◽

Innate Immune ◽

Pathogenic Microorganisms ◽

Immune Systems ◽

Adaptive Immune ◽

Drosophila Model

Like all invertebrates, flies such as Drosophila lack an adaptive immune system and depend on their innate immune system to protect them against pathogenic microorganisms and parasites. In recent years, it appears that the nervous systems of eucaryotes not only control animal behavior but also cooperate and synergize very strongly with the animals’ immune systems to detect and fight potential pathogenic threats, and allow them to adapt their behavior to the presence of microorganisms and parasites that coexist with them. This review puts into perspective the latest progress made using the Drosophila model system, in this field of research, which remains in its infancy.

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Review of phosphocholine substituents on bacterial pathogen glycans: Synthesis, structures and interactions with host proteins

10.32920/14669052.v1 ◽

2021 ◽

Author(s):

Warren W. Wakarchuk

Keyword(s):

Immune System ◽

Bacterial Pathogen ◽

Adaptive Immune System ◽

Infection Process ◽

Innate Immune ◽

Host Proteins ◽

Adaptive Immune ◽

Carbohydrate Components ◽

Multiple Interactions ◽

Structural Aspects

Among the non-carbohydrate components of glycans, the addition of phosphocholine (ChoP) to the glycans of pathogens occurs more rarely than acetylation or methylation, but it has far more potent biological consequences. These arise from ChoP's multiple interactions with host proteins, which are important at all stages of the infection process. These stages include initial adherence to cells, encountering the host's innate immune system and then the adaptive immune system. Thus, in the initial stages of an infection, ChoP groups are an asset to the pathogen, but they can turn into a disadvantage subsequently. In this review, we have focussed on structural aspects of these phenomena. We describe the biosynthesis of the ChoP modification, the structures of the pathogen glycans known to carry ChoP groups and the host proteins that recognize ChoP.

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Pathophysiological and Clinical Aspects of Chronic Rhinosinusitis: Current Concepts

Frontiers in Allergy ◽

10.3389/falgy.2021.741788 ◽

2021 ◽

Vol 2 ◽

Author(s):

Stephan Vlaminck ◽

Frederic Acke ◽

Glenis K. Scadding ◽

Bart N. Lambrecht ◽

Philippe Gevaert

Keyword(s):

Chronic Rhinosinusitis ◽

Inflammatory Responses ◽

Adaptive Immune System ◽

Current Approach ◽

Clinical Aspects ◽

Adaptive Immune ◽

Clinical Observations ◽

Localized Disease ◽

Primary Focus

Adult chronic rhinosinusitis (CRS) is a chronic inflammation of the mucosa of the nose and paranasal sinuses. According to the latest EPOS guidelines CRS should be regarded as primary or secondary with distinction between diffuse and localized disease. Further pathophysiologic research identified different inflammatory patterns leading to the term “endotyping of CRS.” The primary focus of endotyping is to define a dominant inflammatory type allowing for better orientation of therapy. The current approach proposes the differentiation between type 2 (eosinophilic) and non-type 2 inflammatory responses. In this review pathophysiological concepts of CRS will be discussed, focusing on the different inflammatory endotypes of T cells with special attention to the eosinophilic type 2 inflammatory response. The contribution of innate and adaptive immune system responses is presented. The possibility of endotyping based on sinonasal secretions sampling is brought to attention because it is indicative of corticosteroid responsiveness and available to most ENT surgeons. Furthermore, the clinical aspects of the three distinct phenotypes are analyzed in view of their characteristics, the related endoscopic findings, typical radiological imaging, histopathology findings, their relation toward allergy and obvious therapeutical implications. This overview will enable clinicians to relate pathophysiological patterns with clinical observations by explaining the different inflammatory mechanisms, hence providing a better understanding of therapy.

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T Cells and Natural Killer Cells, but Not B Cells or Antibodies, are Affected in Overweight and Obese Saudi Females

Biosciences Biotechnology Research Asia ◽

10.13005/bbra/2769 ◽

2019 ◽

Vol 16 (3) ◽

pp. 545-553

Author(s):

Sawsan Hassan Mahassni

Keyword(s):

High Risk ◽

Adaptive Immune System ◽

Overweight And Obesity ◽

The Body ◽

Innate Immune ◽

Waist To Hip Ratio ◽

Cd4 Counts ◽

University Employees ◽

Adaptive Immune ◽

Age Range

Saudi Arabia has one of the highest adult overweight and obesity rates, especially in females, leading to increased mortality, morbidity, infections, and risk for many diseases. This study determined the counts and percents of lymphocyte subtypes (CD3, CD4, CD8, and CD16 +CD56 cells) and serum IgG, IgA, and IgM concentrations in blood samples collected from sixty-four Saudi female university employees with an age range of 24-52 years. There is only one other study on the counts/numbers of lymphocyte subtypes in overweight and obese Saudi females. Anthropometric measurements were used to categorize the subjects into groups according to the body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC). Results were all compared to the controls. Antibody concentrations were not significantly different. The CD3and CD4 counts were significantly higher for the obese BMI group and the overweight and obese BMI, respectively. The high-risk WHR group had a significantly lower CD 3% and a significantly higher CD16 + CD56 count. The high-risk WC group had significantly higher CD3 and CD4 counts and a significantly lower CD16 + CD56%. Thus, obesity leads to changes in the cellular adaptive and innate immune systems, while not affecting the humoral adaptive immune system.

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