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Immunological Reviews

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https://www.readbyqxmd.com/read/27782339/the-complement-and-contact-activation-systems-partnership-in-pathogenesis-beyond-angioedema
#1
REVIEW
Berhane Ghebrehiwet, Allen P Kaplan, Kusumam Joseph, Ellinor I B Peerschke
The blood plasma contains four biologically important proteolytic cascades, which probably evolved from the same ancestral gene. This in part may explain why each cascade has very similar "initiating trigger" followed by sequential and cascade-like downstream enzymatic activation pattern. The four cascades are: the complement system, the blood clotting cascade, the fibrinolytic system, and the kallikrein-kinin system. Although much has been written about the interplay between all these enzymatic cascades, the cross-talk between the complement and the kinin generating systems has become particularly relevant as this interaction results in the generation of nascent molecules that have significant impact in various inflammatory diseases including angioedema and cancer...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782338/the-versatile-functions-of-complement-c3-derived-ligands
#2
REVIEW
Anna Erdei, Noémi Sándor, Bernadett Mácsik-Valent, Szilvia Lukácsi, Mariann Kremlitzka, Zsuzsa Bajtay
The complement system is a major component of immune defense. Activation of the complement cascade by foreign substances and altered self-structures may lead to the elimination of the activating agent, and during the enzymatic cascade, several biologically active fragments are generated. Most immune regulatory effects of complement are mediated by the activation products of C3, the central component. The indispensable role of C3 in opsonic phagocytosis as well as in the regulation of humoral immune response is known for long, while the involvement of complement in T-cell biology have been revealed in the past few years...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782337/pentraxins-in-the-activation-and-regulation-of-innate-immunity
#3
REVIEW
Kenji Daigo, Antonio Inforzato, Isabella Barajon, Cecilia Garlanda, Barbara Bottazzi, Seppo Meri, Alberto Mantovani
Humoral fluid phase pattern recognition molecules (PRMs) are a key component of the activation and regulation of innate immunity. Humoral PRMs are diverse. We focused on the long pentraxin PTX3 as a paradigmatic example of fluid phase PRMs. PTX3 acts as a functional ancestor of antibodies and plays a non-redundant role in resistance against selected microbes in mouse and man and in the regulation of inflammation. This molecule interacts with complement components, thus modulating complement activation. In particular, PTX3 regulates complement-driven macrophage-mediated tumor progression, acting as an extrinsic oncosuppressor in preclinical models and selected human tumors...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782336/structural-insight-into-proteolytic-activation-and-regulation-of-the-complement-system
#4
REVIEW
Janus A Schatz-Jakobsen, Dennis V Pedersen, Gregers R Andersen
The complement system is a highly complex and carefully regulated proteolytic cascade activated through three different pathways depending on the activator recognized. The structural knowledge regarding the intricate proteolytic enzymes that activate and control complement has increased dramatically over the last decade. This development has been pivotal for understanding how mutations within complement proteins might contribute to pathogenesis and has spurred new strategies for development of complement therapeutics...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782335/the-ins-and-outs-of-complement-driven-immune-responses
#5
REVIEW
Simon Freeley, Claudia Kemper, Gaëlle Le Friec
The complement system represents an evolutionary old and critical component of innate immunity where it forms the first line of defense against invading pathogens. Originally described as a heat-labile fraction of the serum responsible for the opsonization and subsequent lytic killing of bacteria, work over the last century firmly established complement as a key mediator of the general inflammatory response but also as an acknowledged vital bridge between innate and adaptive immunity. However, recent studies particularly spanning the last decade have provided new insights into the novel modes and locations of complement activation and highlighted unexpected additional biological functions for this ancient system, for example, in regulating basic processes of the cell...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782334/terminal-complexes-of-the-complement-system-new-structural-insights-and-their-relevance-to-function
#6
REVIEW
Bryan Paul Morgan, David Walters, Marina Serna, Doryen Bubeck
Complement is a key component of innate immunity in health and a powerful driver of inflammation and tissue injury in disease. The biological and pathological effects of complement activation are mediated by activation products. These come in two flavors: (i) proteolytic fragments of complement proteins (C3, C4, C5) generated during activation that bind specific receptors on target cells to mediate effects; (ii) the multimolecular membrane attack complex generated from the five terminal complement proteins that directly binds to and penetrates target cell membranes...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782333/the-immune-system-s-role-in-sepsis-progression-resolution-and-long-term-outcome
#7
REVIEW
Matthew J Delano, Peter A Ward
Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after "recovery" from acute events...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782332/the-complement-factor-h-related-proteins
#8
REVIEW
Nicholas Medjeral-Thomas, Matthew C Pickering
The role of the complement factor H-related (FHR) proteins in homeostasis, pathogen defense, and autoimmune disease has recently attracted considerable interest. We highlight the exciting research that has contributed to our understanding of the FHR protein family. Unlike factor H, a potent negative regulator of complement C3 activation, the FHR proteins appear to promote C3 activation. These data have important implications for understanding complement-mediated diseases because, depending on the context, the balance between the actions of factor H and the FHR proteins determines the degree of complement activation...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782331/properdin-a-tightly-regulated-critical-inflammatory-modulator
#9
REVIEW
Adam Z Blatt, Sabina Pathan, Viviana P Ferreira
The complement alternative pathway is a powerful arm of the innate immune system that enhances diverse inflammatory responses in the human host. Key to the effects of the alternative pathway is properdin, a serum glycoprotein that can both initiate and positively regulate alternative pathway activity. Properdin is produced by many different leukocyte subsets and circulates as cyclic oligomers of monomeric subunits. While the formation of non-physiological aggregates in purified properdin preparations and the presence of potential properdin inhibitors in serum have complicated studies of its function, properdin has, regardless, emerged as a key player in various inflammatory disease models...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782330/old-dogs-new-tricks-immunoregulatory-properties-of-c3-and-c5-cleavage-fragments
#10
REVIEW
Admar Verschoor, Christian M Karsten, Steven P Broadley, Yves Laumonnier, Jörg Köhl
The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782329/complement-in-removal-of-the-dead-balancing-inflammation
#11
REVIEW
Myriam Martin, Anna M Blom
Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782328/more-than-complementing-tolls-complement-toll-like-receptor-synergy-and-crosstalk-in-innate-immunity-and-inflammation
#12
REVIEW
George Hajishengallis, John D Lambris
Complement and Toll-like receptors (TLRs) play key roles in the host immune response and are swiftly activated by infection or other types of immunological stress. This review focuses on the capacity of complement and TLRs to engage in signaling crosstalk, ostensibly to coordinate immune and inflammatory responses through synergistic or antagonistic (regulatory) interactions. However, overactivation or dysregulation of either system may lead-often synergistically-to exaggerated inflammation and host tissue injury...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782327/evolution-of-the-complement-system-from-defense-of-the-single-cell-to-guardian-of-the-intravascular-space
#13
REVIEW
Michelle Elvington, M Kathryn Liszewski, John P Atkinson
The complement system is an evolutionarily ancient component of immunity that revolves around the central component C3. With the recent description of intracellular C3 stores in many types of human cells, our view of the complement system has expanded. In this article, we hypothesize that a primitive version of C3 comprised the first element of the original complement system and initially functioned intracellularly and on the membrane of single-celled organisms. With increasing specialization and multicellularity, C3 evolved a secretory capacity that allowed it to play a protective role in the interstitial space...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782326/injury-site-specific-targeting-of-complement-inhibitors-for-treating-stroke
#14
REVIEW
Ali Alawieh, Stephen Tomlinson
Cumulative evidence indicates a role for the complement system in both pathology and recovery after ischemic stroke. Here, we review the current understanding of the dual role of complement in poststroke injury and recovery, and discuss the challenges of anti-complement therapies. Most complement directed therapeutics currently under investigation or development systemically inhibit the complement system, but since complement is important for immune surveillance and is involved in various homeostatic activities, there are potential risks associated with systemic inhibition...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782325/complement-component-c3-the-swiss-army-knife-of-innate-immunity-and-host-defense
#15
REVIEW
Daniel Ricklin, Edimara S Reis, Dimitrios C Mastellos, Piet Gros, John D Lambris
As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782324/endothelial-cells-source-barrier-and-target-of-defensive-mediators
#16
REVIEW
Lubka T Roumenina, Julie Rayes, Marie Frimat, Veronique Fremeaux-Bacchi
Endothelium is strategically located at the interface between blood and interstitial tissues, placing thus endothelial cell as a key player in vascular homeostasis. Endothelial cells are in a dynamic equilibrium with their environment and constitute concomitantly a source, a barrier, and a target of defensive mediators. This review will discuss the recent advances in our understanding of the complex crosstalk between the endothelium, the complement system and the hemostasis in health and in disease. The first part will provide a general introduction on endothelial cells heterogeneity and on the physiologic role of the complement and hemostatic systems...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782323/a-journey-through-the-lectin-pathway-of-complement-mbl-and-beyond
#17
REVIEW
Peter Garred, Ninette Genster, Katrine Pilely, Rafael Bayarri-Olmos, Anne Rosbjerg, Ying Jie Ma, Mikkel-Ole Skjoedt
Mannose-binding lectin (MBL), collectin-10, collectin-11, and the ficolins (ficolin-1, ficolin-2, and ficolin-3) are soluble pattern recognition molecules in the lectin complement pathway. These proteins act as mediators of host defense and participate in maintenance of tissue homeostasis. They bind to conserved pathogen-specific structures and altered self-antigens and form complexes with the pentraxins to modulate innate immune functions. All molecules exhibit distinct expression in different tissue compartments, but all are found to a varying degree in the circulation...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782322/preformed-mediators-of-defense-gatekeepers-enter-the-spotlight
#18
Daniel Ricklin, John D Lambris
No abstract text is available yet for this article.
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782321/protection-of-host-cells-by-complement-regulators
#19
REVIEW
Christoph Q Schmidt, John D Lambris, Daniel Ricklin
The complement cascade is an ancient immune-surveillance system that not only provides protection from pathogen invasion but has also evolved to participate in physiological processes to maintain tissue homeostasis. The alternative pathway (AP) of complement activation is the evolutionarily oldest part of this innate immune cascade. It is unique in that it is continuously activated at a low level and arbitrarily probes foreign, modified-self, and also unaltered self-structures. This indiscriminate activation necessitates the presence of preformed regulators on autologous surfaces to spare self-cells from the undirected nature of AP activation...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782320/innate-immune-mediators-in-cancer-between-defense-and-resistance
#20
REVIEW
Pedro Berraondo, Luna Minute, Daniel Ajona, Leticia Corrales, Ignacio Melero, Ruben Pio
Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors...
November 2016: Immunological Reviews
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