Nonspecific Lines of Defense Again (original) (raw)

Cell triggering by activated complement components

Immunology Letters, 1985

Activation of the complement system includes protein interactions, conversion of proteins from a zymogen form to active serine proteinases and proteolytic cleavages. Six of the twenty complement components which are known today bear catalytic sites and act specifically on other proteins of the complement system. This leads to generation of cleavage products which express many biological activities and are the subjects of this review. Since detailed reviews on the molecular dynamics of complement activation and regulation have been recently published [1-6], this subject is hereby only briefly discussed. Complement activation may proceed via the classical and/or the alternative pathway depending on the activating substance. Thus, for example, antigenbound antibodies of the IgG and IgM classes set the classical pathway (CP) into motion whereas polysaccharides in particulate form activate primarily the alternative pathway (AP). The components which comprise each pathway and their location in the complement cascade are depicted in Fig. 1. Clq, Clr, Cls, C4, C2, C3, calcium and magnesium ions participate in CP activation whereas Factor B, Factor D, C3, properdin and magnesium ions in AP activation. Both pathways are highly regulated by the serum proteins C1 inhibitor (CP), C4 binding protein

Complement System Part II: Role in Immunity

Frontiers in Immunology, 2015

The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b-9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. Keywords: complement system, adaptive immunity, crosstalk TLR-complement, pathogen strategies for immune evasion, complement in cancer, complement and innate immunity, complement-related diseases, anaphylatoxins

Complement System and Its Role in Immune Responses

eLS, 2012

Based in part on the previous version of this eLS article 'Complement' (2005) by M Claire H Holland and John D Lambris. The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc.), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. Dysregulation of complement activity has, therefore, been connected to various diseases, including autoimmune conditions, thrombotic pathologies and infections. Protein Structure Concentration (mg/mL) Cellular sources Key function Alternative pathway Factor B 93 kDa 210 Hepatocyte, mononuclear phagocytes, epithelial and endothelial cells, adipocytes, fibroblasts Catalytic subunit of AP C3 convertase, forms part of the C5 convertase

Activation of the complement system at the interface between blood and artificial surfaces

Biomaterials, 1988

The interaction between blood and the artificial devices used in baemodialysis results in the activation of the immune system. Complement activation is known to play a key role in the production of inflammatory mediators. This article describes the complement system and the way in which it is triggered in the patient undergoing haemodialysis. It highlights those factors thought to be of particular importance in the pathogenesis of adverse reactions and targets them as obstacles to be overcome in the future design of biocompatible materials.

The Pathways of Complement

2008

The natural world has developed very effective methods for dealing with pathogens that are invading an organism. By taking inspiration from the in-built, innate, response this paper develops a new algorithm that mimics activation path of the Alternative Pathway of Complement. The Alternative Pathway is triggered by cell surfaces. If the surfaces display safe characteristics then a strong suppression process prevents activation. In the case of non-safe surfaces a positive feedback loop rapidly identifies the location marking it for removal by phagocytosis.

Complement and humoral immunity

Vaccine, 2008

The complement system was discovered almost a century ago as an important effector in antibody-dependent killing of microorganisms. Since this early period much was learned about the biochemistry and structure of complement proteins and their function in mediating inflammation. More recently, a prominent role for complement was identified in linkage of innate and adaptive immunity. In this review, I will discuss our current understanding of the importance of complement in enhancing the humoral immune response to both model antigens and pathogens. As discussed below, it is evident that the complement system participates in marking of "foreign" pathogens and "presenting" them to B cells in a manner that enhances both antibody production and long term memory. In this special issue of Vaccine, we see examples of how complement is critical in the immune response to bacterial and viral pathogens. Moreover, the finding that most organisms have co-evolved proteins to evade complement detection underscores its importance in host protection.

Studies of antibody and complement function in host defense against bacterial infection

Immunology Letters, 1987

We have been engaged in a systematic study of the factors that control the lysis of gram negative bacteria. It has become clear that there has evolved a series of host defense mechanisms against bacterial infection. Bacteria on the other hand, have evolved a series of stratagems to avoid destruction. In the case of gram negative bacteria one mechanism that acts to kill bacteria is direct bactericidal action of complement. In this case the late-acting components of the complement cascade are deposited on the bacterial surface to form a doughnut-like structure termed the membrane attack complex (MAC). This complex with a hydrophobic outer surface and a hydrophilic center penetrates the bacterial cell wall ultimately causing death. The Enterobacteriaceae have evolved a protective mechanism that allows the MAC to be deposited on the surface in association with structures that do not permit its insertion into the bacterial wall outer membrane. With completion of deposition of the late-acting components of complement, the MAC becomes increasingly hydrophobic. Instead of successful insertion into membrane lipid the MAC is shed. One structure that plays a role in diverting MAC from successful insertion