scholarly journals Potent Stimulation of the Innate Immune System by aLeishmania brasiliensis Recombinant Protein

2001 ◽  
Vol 69 (9) ◽  
pp. 5270-5277 ◽  
Author(s):  
Monamaris M. Borges ◽  
Antonio Campos-Neto ◽  
Paul Sleath ◽  
Keneth H. Grabstein ◽  
Philip J. Morrissey ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Reticuloendothelial System ◽  
Scid Mice ◽  
Innate Immune ◽  
Initiation Factor ◽  
Interleukin 12 ◽  
Microbial World

ABSTRACT The interaction of the innate immune system with the microbial world involves primarily two sets of molecules generally known as microbial pattern recognition receptors and microbial pattern recognition molecules, respectively. Examples of the former are the Toll receptors present particularly in macrophages and dendritic cells. Conversely, the microbial pattern recognition molecules are conserved protist homopolymers, such as bacterial lipopolysaccharides, lipoteichoic acids, peptidoglycans, glucans, mannans, unmethylated bacterial DNA, and double-strand viral RNA. However, for protists that lack most of these molecules, such as protozoans, the innate immune system must have evolved receptors that recognize other groups of microbial molecules. Here we present evidence that a highly purified protein encoded by a Leishmania brasiliensis gene may be one such molecule. This recombinant leishmanial molecule, a homologue of eukaryotic ribosomal elongation and initiation factor 4a (LeIF), strongly stimulates spleen cells from severe combined immunodeficient (SCID) mice to produce interleukin-12 (IL-12), IL-18, and high levels of gamma interferon. In addition, LeIF potentiates the cytotoxic activity of the NK cells of these animals. Because LeIF is a conserved molecule and because SCID mice lack T and B lymphocytes but have a normal innate immune system (normal reticuloendothelial system and NK cells), these results suggest that proteins may also be included as microbial pattern recognition molecules. The nature of the receptor involved in this innate recognition is unknown. However, it is possible to exclude the Toll receptor Tlr4 as a putative LeIF receptor because the gene encoding this receptor is defective in C3H/HeJ mice, the mouse strain used in the present studies.

scholarly journals Therapeutic Interventions into Innate Immune Diseases by Means of Aptamers

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 955
Author(s):  
Farzana Yasmeen ◽  
Hana Seo ◽  
Nasir Javaid ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Crucial Role ◽  
Innate Immune System ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Immune System Diseases ◽  
Target Molecules ◽  
Molecular Patterns ◽  
Recognition Receptor

The immune system plays a crucial role in the body’s defense system against various pathogens, such as bacteria, viruses, and parasites, as well as recognizes non-self- and self-molecules. The innate immune system is composed of special receptors known as pattern recognition receptors, which play a crucial role in the identification of pathogen-associated molecular patterns from diverse microorganisms. Any disequilibrium in the activation of a particular pattern recognition receptor leads to various inflammatory, autoimmune, or immunodeficiency diseases. Aptamers are short single-stranded deoxyribonucleic acid or ribonucleic acid molecules, also termed “chemical antibodies,” which have tremendous specificity and affinity for their target molecules. Their features, such as stability, low immunogenicity, ease of manufacturing, and facile screening against a target, make them preferable as therapeutics. Immune-system–targeting aptamers have a great potential as a targeted therapeutic strategy against immune diseases. This review summarizes components of the innate immune system, aptamer production, pharmacokinetic characteristics of aptamers, and aptamers related to innate-immune-system diseases.

scholarly journals The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors

2000 ◽  
Vol 97 (25) ◽  
pp. 13766-13771 ◽  
Author(s):  
A. Ozinsky ◽  
D. M. Underhill ◽  
J. D. Fontenot ◽  
A. M. Hajjar ◽  
K. D. Smith ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors

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

2010 ◽  
Vol 16 (3) ◽  
pp. 131-137 ◽  
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.

scholarly journals NK Cell Memory to Cytomegalovirus: Implications for Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 394
Author(s):  
Calum Forrest ◽  
Ariane Gomes ◽  
Matthew Reeves ◽  
Victoria Male
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Innate Immune System ◽  
Vaccine Development ◽  
Nk Cell ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Murine Cytomegalovirus ◽  
Immune Memory ◽  
Cell Memory

Natural killer (NK) cells are innate lymphoid cells that recognize and eliminate virally-infected and cancerous cells. Members of the innate immune system are not usually considered to mediate immune memory, but over the past decade evidence has emerged that NK cells can do this in several contexts. Of these, the best understood and most widely accepted is the response to cytomegaloviruses, with strong evidence for memory to murine cytomegalovirus (MCMV) and several lines of evidence suggesting that the same is likely to be true of human cytomegalovirus (HCMV). The importance of NK cells in the context of HCMV infection is underscored by the armory of NK immune evasion genes encoded by HCMV aimed at subverting the NK cell immune response. As such, ongoing studies that have utilized HCMV to investigate NK cell diversity and function have proven instructive. Here, we discuss our current understanding of NK cell memory to viral infection with a focus on the response to cytomegaloviruses. We will then discuss the implications that this will have for the development of a vaccine against HCMV with particular emphasis on how a strategy that can harness the innate immune system and NK cells could be crucial for the development of a vaccine against this high-priority pathogen.

scholarly journals Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2226
Author(s):  
Israa Shihab ◽  
Bariaa A. Khalil ◽  
Noha Mousaad Elemam ◽  
Ibrahim Y. Hachim ◽  
Mahmood Yaseen Hachim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

scholarly journals Structural aspects of molecular recognition in the immune system. Part II: Pattern recognition receptors (IUPAC Technical Report)

2014 ◽  
Vol 86 (10) ◽  
pp. 1483-1538 ◽  
Author(s):  
John A. Robinson ◽  
Kerstin Moehle
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Immune Responses ◽  
Signaling Pathways ◽  
Innate Immune System ◽  
Pattern Recognition Receptors ◽  
Innate Immune ◽  
Helicase Domain ◽  
Downstream Signaling ◽  
Adaptive Immune

Abstract The vertebrate immune system uses pattern recognition receptors (PRRs) to detect a large variety of molecular signatures (pathogen-associated molecular patterns, PAMPs) from a broad range of different invading pathogens. The PAMPs range in size from relatively small molecules, to others of intermediate size such as bacterial lipopolysaccharide, lipopeptides, and oligosaccharides, to macromolecules such as viral DNA, RNA, and pathogen-derived proteins such as flagellin. Underlying this functional diversity of PRRs is a surprisingly small number of structurally distinct protein folds that include leucine-rich repeats in Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the DExH box helicase domain in RIG-like receptors (RLRs), and C-type lectin domains (CTLDs) in the C-type lectins. Following PAMP recognition by the PRRs, downstream signaling pathways activate the innate immune system to respond to invading pathogenic organisms. The resulting stimulatory response is also vital for a balanced adaptive immune response to the pathogen, mediated by circulating antibodies and/or cytotoxic T cells. However, an aberrant stimulation of the innate immune system can also lead to excessive inflammatory and toxic stress responses. Exciting opportunities are now arising for the design of small synthetic molecules that bind to PRRs and influence downstream signaling pathways. Such molecules can be useful tools to modulate immune responses, for example, as adjuvants to stimulate adaptive immune responses to a vaccine, or as therapeutic agents to dampen aberrant immune responses, such as inflammation. The design of agonists or antagonists of PRRs can now benefit from a surge in knowledge of the 3D structures of PRRs, many in complexes with their natural ligands. This review article describes recent progress in structural studies of PRRs (TLRs, NLRs, CTLs, and RLRs), which is required for an understanding of how they specifically recognize structurally diverse “foreign” PAMPs amongst a background of other “self” molecules, sometimes closely related in structure, that are present in the human body.

scholarly journals Role of pattern recognition receptors of the neurovascular unit in inflamm-aging

2017 ◽  
Vol 313 (5) ◽  
pp. H1000-H1012 ◽  
Author(s):  
Imola Wilhelm ◽  
Ádám Nyúl-Tóth ◽  
Mihály Kozma ◽  
Attila E. Farkas ◽  
István A. Krizbai
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Chronic Inflammation ◽  
Blood Brain Barrier ◽  
Innate Immune System ◽  
Neurovascular Unit ◽  
Innate Immune ◽  
Brain Barrier ◽  
Pyrin Domain ◽  
The Brain

Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes.

scholarly journals Pattern Recognition Receptors in Cancer Progression and Metastasis

2015 ◽  
Vol 8 ◽  
pp. CGM.S24314 ◽  
Author(s):  
Sanjay Pandey ◽  
Saurabh Singh ◽  
Vandana Anang ◽  
Anant N. Bhatt ◽  
K. Natarajan ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Tumor Cell ◽  
Cancer Progression ◽  
Innate Immune System ◽  
Pattern Recognition Receptors ◽  
Innate Immune ◽  
Preventive Strategy ◽  
Chronic Activation

The innate immune system is an integral component of the inflammatory response to pathophysiological stimuli. Toll-like receptors (TLRs) and inflammasomes are the major sensors and pattern recognition receptors (PRRs) of the innate immune system that activate stimulus (signal)-specific proinflammatory responses. Chronic activation of PRRs has been found to be associated with the aggressiveness of various cancers and poor prognosis. Involvement of PRRs was earlier considered to be limited to infection- and injury-driven carcinogenesis, where they are activated by pathogenic ligands. With the recognition of damage-associated molecular patterns (DAMPs) as ligands of PRRs, the role of PRRs in carcinogenesis has also been implicated in other non-pathogen-driven neoplasms. Dying (apoptotic or necrotic) cells shed a plethora of DAMPs causing persistent activation of PRRs, leading to chronic inflammation and carcinogenesis. Such chronic activation of TLRs promotes tumor cell proliferation and enhances tumor cell invasion and metastasis by regulating pro-inflammatory cytokines, metalloproteinases, and integrins. Due to the decisive role of PRRs in carcinogenesis, targeting PRRs appears to be an effective cancer-preventive strategy. This review provides a brief account on the association of PRRs with various cancers and their role in carcinogenesis.

scholarly journals Innate Immunity and Neuroinflammation

2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Author(s):  
Abhishek Shastri ◽  
Domenico Marco Bonifati ◽  
Uday Kishore
Keyword(s):  
Central Nervous System ◽  
Pattern Recognition ◽  
Innate Immunity ◽  
Nervous System ◽  
Immune System ◽  
Innate Immune System ◽  
Close Relation ◽  
Innate Immune ◽  
Beneficial Effects ◽  
Chronic Neuroinflammation

Inflammation of central nervous system (CNS) is usually associated with trauma and infection. Neuroinflammation occurs in close relation to trauma, infection, and neurodegenerative diseases. Low-level neuroinflammation is considered to have beneficial effects whereas chronic neuroinflammation can be harmful. Innate immune system consisting of pattern-recognition receptors, macrophages, and complement system plays a key role in CNS homeostasis following injury and infection. Here, we discuss how innate immune components can also contribute to neuroinflammation and neurodegeneration.

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