Search results for "complement pathway"

Complement activation and innate immunity

2007

Combined complete C5 and partial C4 deficiency in humans: clinical consequences and complement-mediated functions in vitro.

1990

A family is described with two siblings who suffered at different times from a single episode of meningococcal meningitis by Neisseria meningitidis groups B and C, respectively. In the two subjects, hemolytically active fifth component of complement (C5) was not detectable and antigenic C5 was less than 0.05% and less than 0.7% of normal, respectively. Repletion of sera by purified human C5 (70 micrograms/ml) restored total complement hemolytic activities. The asymptomatic first degree family members had C5 levels compatible with a heterozygous state of C5 deficiency. C4 allotyping revealed an inherited partial deficiency (Q0) of C4A and C4B in the family with a combined C4AQ0 and C4BQ0 het…

Complement receptors on lymphocytes

1981

Cloning and expression of the complement receptor glycoprotein C from Herpesvirus simiae (herpes B virus): protection from complement-mediated cell l…

2003

Simian herpes B virus (SHBV) is the herpes simplex virus (HSV) homologue for the species MACACA: Unlike in its natural host, and unlike other animal herpesviruses, SHBV causes high mortality in accidentally infected humans. SHBV-infected cells, like those infected with HSV-1 and equine herpesvirus types 1 and 4, express complement C3 receptor activity. To study immunoregulatory functions involved in susceptibility/resistance against interspecies transmission, the SHBV glycoprotein C (gC(SHBV)) gene (encoding 467 aa) was isolated. Sequence analysis revealed amino acid identity with gC proteins from HSV-2 (46.9 %), HSV-1 (44.5 %) and pseudorabies virus (21.2 %). Highly conserved cysteine resi…

The modulation of immune complex aggregation by classical pathway-mediated reactions.

1985

Abstract Classical pathway (CP)-triggered reactions of complement-modulated immune complex(IC) aggregation (tetanus toxoid/human anti-tetanus toxoid-IgG; ICs of equivalence) were investigated turbidimetrically during the early stages of reaction. Monospecific Fab'- or Fab-fragments (rabbit) directed against certain complement components were used to block the complement function in normal human serum (NHS). Additionally, parts of the reactions were studied using purified complement components. C1q in serum generated by the addition of EDTA as well as purified C1q were found to increase the IC aggregation. In contrast to C1q, macromolecular C1 is able to inhibit IC aggregation, whereas addit…

Importance of Factors H and I for the Adherence of C3b-Coated Erythrocytes to Cells

1983

Abstract The role of cell membrane-associated human factor H for the binding of cell-bound Cab to complement receptor-carrying (CR + ) cells was investigated. Pretreatment of CR + cells with antibodies to factor H inhibited the adherence of Cab-coated red cells to human tonsil lymphocytes (TL) and peripheral blood monocytes (Mo). The Cab receptor reactivity of human polymorphonuclear leucocytes (PMN) was not influenced and the one of Raji lymphoblastoid cells only slightly influenced; iC3b and Cad receptor reactivity was in no case affected. When diisopropylfluorophosphate (DFP) in a concentration of 0.1 mM was present during pretreatment of the CR + cells with anti H, the antibodies gained…

Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes.

2011

AbstractSequestration of parasitized erythrocytes and dysregulation of the coagulation and complement system are hallmarks of severe Plasmodium falciparum malaria. A link between these events emerged through the discovery that the parasite digestive vacuole (DV), which is released together with infective merozoites into the bloodstream, dually activates the intrinsic clotting and alternative complement pathway. Complement attack occurs exclusively on the membrane of the DVs, and the question followed whether DVs might be marked for uptake by polymorphonuclear granulocytes (PMNs). We report that DVs are indeed rapidly phagocytosed by PMNs after schizont rupture in active human serum. Uptake …

Cutting Edge: IL-6–Driven Immune Dysregulation Is Strictly Dependent on IL-6R α-Chain Expression

2020

Abstract IL-6 binds to the IL-6R α-chain (IL-6Rα) and signals via the signal transducer gp130. Recently, IL-6 was found to also bind to the cell surface glycoprotein CD5, which would then engage gp130 in the absence of IL-6Rα. However, the biological relevance of this alternative pathway is under debate. In this study, we developed a mouse model, in which murine IL-6 is overexpressed in a CD11c-Cre–dependent manner. Transgenic mice developed a lethal immune dysregulation syndrome with increased numbers of Ly-6G+ neutrophils and Ly-6Chi monocytes/macrophages. IL-6 overexpression promoted activation of CD4+ T cells while suppressing CD5+ B-1a cell development. However, additional ablation of …

C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation

2015

Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa−/−) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa−/− mi…

In vitro synthesis of factor B of the alternative pathway of complement activation by mouse peritoneal macrophages

1976

Factor B of the alternative pathway of complement activation was shown to be synthesized and secreted by unstimulated mouse peritoneal macrophages. The activity of B in the culture supernatants from macrophage monolayers was detected by consumption of C3 in reaction mixtures containing supernatant and guinea pig factors C3, D and insoluble C3b. Using a monospecific antiserum, factor B in concentrated culture supernatants was shown by immunodiffusion and immunoelectrophoresis to be identical to factor B in mouse plasma and to form a characteristic complex with cobra venom factor in the presence of D. A steady rate of factor B secretion was observed for 4 days providing the medium was changed…