T-cell regulation: With complements from innate immunity

Washington University School of Medicine, Department of Internal Medicine, Division of Rheumatology, Campus Box 8045, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 02/2007; 7(1):9-18. DOI: 10.1038/nri1994
Source: PubMed


The complement system was traditionally known as an effector arm of humoral immunity. Today we also recognize it as a main element of the innate immune system. In blood and other body fluids complement is a first line of defence against pathogens, because it becomes fully active within seconds. Active complement fragments attach to the invading pathogen to promote opsonization and lysis, triggering a local inflammatory response. This Review focuses on the evolving role of the complement system in the regulation of T-cell responses, from directing the initiation phase, through driving lineage commitment, to regulating the contraction phase.

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Available from: Claudia Kemper, Dec 28, 2013
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    • "While the classical pathway (CP) and lectin pathway (LP) are initiated in response to danger associated or pathogen associated molecular patterns (e.g. immune complexes and microbial sugars), the alternative pathway (AP) is continuously auto-activated at low level (so called tick-over activation) (Kemper and Atkinson, 2007). Several soluble and membrane-bound host regulators are in place to restrict complement activation and amplification on self surfaces (Dunkelberger and Song, 2010; Ricklin et al., 2010; Rodriguez de Cordoba et al., 1985). "
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    ABSTRACT: Malaria remains one of the world's deadliest diseases. Plasmodium falciparum is responsible for the most severe and lethal form of human malaria. P. falciparum's life cycle involves two obligate hosts: human and mosquito. From initial entry into these hosts, malaria parasites face the onslaught of the first line of host defence, the complement system. In this review, we discuss the complex interaction between complement and malaria infection in terms of hosts immune responses, parasite survival and pathogenesis of severe forms of malaria. We will focus on the role of complement receptor 1 and its associated polymorphisms in malaria immune complex clearance, as a mediator of parasite rosetting and as an entry receptor for P. falciparum invasion. Complement evasion strategies of P. falciparum parasites will also be highlighted. The sexual forms of the malaria parasites recruit the soluble human complement regulator Factor H to evade complement-mediated killing within the mosquito host. A novel evasion strategy is the deployment of parasite organelles to divert complement attack from infective blood stage parasites. Finally we outline the future challenge to understand the implications of these exploitation mechanisms in the interplay between successful infection of the host and pathogenesis observed in severe malaria. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Molecular Immunology 03/2015; 67(1). DOI:10.1016/j.molimm.2015.03.006 · 2.97 Impact Factor
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    • "The systemic production of complement by liver did not affect cancer as was evident by a similar growth of implanted tumors in C3 −/− and WT mice and by deposition of complement activation end products in resected tumors from C3 −/− mice. The importance of complement proteins in the cell-cell interactions has previously been shown in the antigen-presenting cells (APCs) and T cell cognate complexes in the T cell/APC interface, where complement proteins secreted by APCs regulate T cell proliferation and differentiation (Kemper and, Atkinson 2007; Longhi et al., 2006; Peng et al., 2008; Sacks, 2010; Strainic et al., 2008). "
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    ABSTRACT: We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.
    Cell Reports 03/2014; 6(6). DOI:10.1016/j.celrep.2014.02.014 · 8.36 Impact Factor
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    • "The complement system , as an important part of the innate im - mune system , mediates several major effector functions and mod - ulates adaptive immune responses . Particularly , mammalian C3d , the terminal product of C3 fragmentation , has been shown to mediate humoral immune response through the interaction with CR2 expressed on B - cells ( Fearon and Carroll , 2000 ; Holers and Kulik , 2007 ) , and interaction of C3b , an initial form of C3 fragmen - tation , with MCP and DAF expressed on T - cells and macrophages , to modify adaptive immune response by controlling T - cell activa - tion and inactivation ( Kemper and Atkinson , 2007 ) . It is still unclear if the immune - modulating function mediated by mamma - lian C3 fragments ( C3b , iC3b and C3d ) and their binding to leuko - cyte occurs in zebrafish . "
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    ABSTRACT: Zebrafish is recently emerging as a model species for the study of immunology and human diseases. Complement system is the humoral backbone of the innate immune defense, and our knowledge as such in zebrafish has dramatically increased in the recent years. This review summarizes the current research progress of zebrafish complement system. The global searching for complement components in genome database, together with published data, has unveiled the existence of all the orthologues of mammalian complement components identified thus far, including the complement regulatory proteins and complement receptors, in zebrafish. Interestingly, zebrafish complement components also display some distinctive features, such as prominent levels of extrahepatic expression and isotypic diversity of the complement components. Future studies should focus on the following issues that would be of special importance for understanding the physiological role of complement components in zebrafish: conclusive identification of complement genes, especially those with isotypic diversity; analysis and elucidation of function and mechanism of complement components; modulation of innate and adaptive immune response by complement system; and unconventional roles of complement-triggered pathways.
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