Literature

Complement activation in susceptibility to neonatal sepsis.

Incidence of bacterial sepsis during the neonatal period:
The incidence of bacterial sepsis during the neonatal period is high. Innate immunity plays an
important role in the defense of neonates against invasive infections. Mannan-binding lectin (MBL),
L-ficolin, and H-ficolin recognize microorganisms and activate the complement system via MBLassociated
serine proteases (MASPs). However, the entire lectin pathway has never been studied in
patients with sepsis...

Pentraxins, Innate immunity and Inflammation

Innate immunity is a first line of host defense against pathogens, it plays a key role in the activation of adaptive immunity and in the maintenance of tissue repair. Recognition of pathogens and damaged tissues is mediated by pattern recognition receptors (PRRs) that are part of both the cellular and humoral arms of innate defense mechanisms. Toll-like receptors (TLRs), scavenger receptors, and lectin receptors are cellular PRRs, whereas the humoral arm of innate immunity includes collectins (mannose-binding lectin, surfactant proteins A and D, C1q), ficolins, and pentraxins.

Neutrophil proteins in innate host defense

Neutrophils represent roughly 50-70 % of the total white blood cell population in human. Together with basophils and eosinophils, they compose the polymorphonuclear cell family (PMNs). Structural hallmarks of a neutrophil are its multilobed nucleus and the abundant storage granules in the cytoplasm. Neutrophils undergo a process called chemotaxis, which allows them to migrate toward sites of infection or inflammation. They are attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Cell surface receptors are able to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-gamma), C3a/b and C5a, which these cells use to direct the path...

Complement markers of renal disease and injury

Complement is a major mediator system in pathogenesis of various kidney diseases. The presence and localization of complement components in glomerulus and/or the tubulo-interstitial area provides diagnostic tools for several human renal diseases (Table). Determination of complement deposition also serves a valuable supplementary role in diagnosis of antibody mediated rejection in kidney transplantation. Particularly important has been the inclusion of C4d staining in the Banff scoring criteria for assessment of renal transplant pathology, in 2003. In addition, the application of anti-complement antibodies is of utmost importance for studying experimental models of kidney disease in rat and mouse. A specific example...

The protein C anticoagulant pathway: Nexus between coagulation and inflammation

There is growing evidence that the coagulation system co-evolved with the innate immune system. There is a remarkable degree of integration in their signaling pathways and regulatory circuits following tissue injury and microbial invasion: inflammatory mediators generate procoagulant signals and intravascular thrombosis activates multiple components of the innate immune system. The nexus between coagulation and inflammation is most obviously demonstrated by the successful use of recombinant activated protein C (APC) for the treatment of sepsis. 

Intestinal inflammation

Gastrointestinal tissue is constantly under attack by luminal bacteria, viruses and other harmful microbiota. Epithelial cells and the immune cells of mucosal tissues, form an important line of defense. Mucosal damage is pivotal to the onset of intestinal inflammation and the etiology of, for example, inflammatory bowel disease (IBD). It is, therefore, essential to understand the mechanisms underlying mucosal damage. Epithelial cells form a biological barrier that prevents interaction of luminal pathogens with the immune cells in the lamina propria (1). The crypts of the small gut are protected against microbiota by an array of microbial peptides among which defensins (e.g. HD5), lysozyme and phospholipase A2. These peptides are produced...

Complement and endogenous danger

Immunity has evolved from recognition of tissue damage rather than foreignness. Therefore, also endogenous danger signals (such as apoptosis, membrane fragments etc) are capable of stimulating the complement system. The complement components with clear afferent functions C1q, mannan binding lectin (MBL) and C3, are the essential soluble danger sensing proteins, which are activated by both endogenous and exogenous stimuli. This afferent arm of the complement system is critical for tissue homeostasis under steady-state conditions as well as in response to infection and cell injury. It translates the danger information into specific efferent cellular responses by interaction with specific receptors on distinct cells...