Topic
Alternative complement pathway
About: Alternative complement pathway is a research topic. Over the lifetime, 4608 publications have been published within this topic receiving 202183 citations. The topic is also known as: complement activation, alternative pathway & GO:0006957.
Papers published on a yearly basis
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Papers
TL;DR: An updated view of the function, structure and dynamics of the complement network is described, its interconnection with immunity at large and with other endogenous pathways is highlighted, and its multiple roles in homeostasis and disease are illustrated.
Abstract: Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.
3,488 citations
TL;DR: Results strongly suggest that the classical and alternative pathways to NF-κB activation have distinct regulatory functions, one that is mostly involved in innate immunity and the other in adaptive immunity.
2,590 citations
TL;DR: It is shown that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium, implicating HF1 function in the pathogenetic mechanisms underlying AMD.
Abstract: Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of ≈900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (I62V, χ2 = 26.1 and P = 3.2 × 10-7 and Y402H, χ2 = 54.4 and P = 1.6 × 10-13). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population.
2,182 citations
TL;DR: The innate immune system is the only defence weapon of invertebrates and a fundamental defence mechanism of fish and plays an instructive role in the acquired immune response and homeostasis and is therefore equally important in higher vertebrates.
2,095 citations
TL;DR: This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
Abstract: The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
1,457 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 20 |
| 2024 | 58 |
| 2023 | 98 |
| 2022 | 183 |
| 2021 | 132 |
| 2020 | 121 |