Topic
C8 complex
About: C8 complex is a research topic. Over the lifetime, 45 publications have been published within this topic receiving 3112 citations. The topic is also known as: C8 & complement C8.
Papers
TL;DR: Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, NeISSeria gonorrhoeae.
Abstract: The complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement-mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies.
740 citations
TL;DR: The pathophysiologic events pertinent to the complement system that accompany meningococcal sepsis in humans are reviewed and some of the newly described protein vaccine antigens interact with complement components and have sparked considerable research interest.
Abstract: Despite considerable advances in the understanding of the pathogenesis of meningococcal disease, this infection remains a major cause of morbidity and mortality globally. The role of the complement system in innate immune defenses against invasive meningococcal disease is well established. Individuals deficient in components of the alternative and terminal complement pathways are highly predisposed to invasive, often recurrent meningococcal infections. Genome-wide analysis studies also point to a central role for complement in disease pathogenesis. Here we review the pathophysiologic events pertinent to the complement system that accompany meningococcal sepsis in humans. Meningococci use several often redundant mechanisms to evade killing by human complement. Capsular polysaccharide and lipooligosaccharide glycan composition play critical roles in complement evasion. Some of the newly described protein vaccine antigens interact with complement components and have sparked considerable research interest.
203 citations
TL;DR: This review provides an update on the recent findings on the diverse mechanisms by which N. meningitidis avoids complement-mediated killing, and how polymorphisms in genes encoding human complement proteins affect susceptibility to this important human pathogen.
164 citations
TL;DR: This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.
Abstract: The serum of a 29-year-old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well, eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.
84 citations
TL;DR: The complement cascade is reviewed with particular reference to its importance in host defense against bacterial diseases, to compare and contrast neisserial disease in complement-deficient and complementsufficient individuals, and to examine the immunologic basis for prevention of neiss aerial infections in complement -deficient individuals.
Abstract: The importance of the complement system in host defense against systemic infection caused by neisseriae is emphasized by a number of clinical observations documenting the importance of antibody-dependent, complement-mediated serum bactericidal activity in protection from systemic meningococcal disease (17) and the well-recognized association between the resistance of gonococci to complement-dependent serum bactericidal activity and the development of disseminated gonococcal infection (46, 49). Moreover, individuals with inherited complement deficiencies have a markedly increased risk (ca. 6,000-fold) of acquiring systemic neisserial infections and are subject to recurrent episodes of systemic meningococcal and gonococcal infections (37, 43). The purpose of this report is to review the complement cascade with particular reference to its importance in host defense against bacterial diseases, to compare and contrast neisserial disease in complement-deficient and complementsufficient individuals, to examine the molecular and functional basis for the particular importance of complement in host defense against these infections, and to examine the immunologic basis for prevention of neisserial disease in complement-deficient individuals.
78 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2014 | 2 |
| 2013 | 2 |
| 2011 | 2 |
| 2010 | 1 |
| 2009 | 2 |
| 2008 | 4 |