Complement and parasitic trematodes

The complement (C) system acts as a barrier to protect our bodies against invading pathogens. It may react to cytophilic antibodies or directly to foreign molecules presented by the intruder. As well as their cytotoxic activity, C components can attract and attach leucocytes to the surface of the foreign body, and activate them to kill it. Zvi Fishelson describes various strategies used by a parasitic trematode to escape immune damage in the face of potent immune surveillance by C and other effector mechanisms.     

补体系统与细胞因子的相互作用

补体和细胞因子均为免疫系统中的重要组成部分,共同参与了机体抵抗病原体的防御反应、免疫调节以及机体的免疫病理性损伤反应。Glq、C3及其活性片段,c5及其活性片段以及其它的外体成分与TNF-α,IFN-γ、IL-1、IL-6等炎性细胞因子在炎症过程中通过各种直接或间接的途径相互作用,二者之间的平衡最终决定了炎症的发展与转归。文章不仅总结了新近研究所表明的补体对CK的调节作用,而且介绍了近年来关于细胞因子调节补体研究的新发展。     

补体系统及其在肝损伤再生中的作用

补体系统是机体免疫防御机制的重要组成部分,参与免疫识别和防御。近年来,系统研究发现补体除免疫调节外,还具有参与生殖发育、成骨、组织和器官再生等重要生理机能的作用。多项研究报道了补体活化和各种肝损伤／再生的关系,对此进行综述,以期促进对补体多样性功能的了解。     

Incorporation of Host Complement Regulatory Proteins into Newcastle Disease Virus Enhances Complement Evasion

Newcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor selective and is currently being considered as a clinical oncolytic virus and vaccine vector. In this study, we analyzed the effect of complement on the neutralization of NDV purified from embryonated chicken eggs, a common source for virus production. Fresh normal human serum (NHS) neutralized NDV by multiple pathways of complement activation, independent of neutralizing antibodies. Neutralization was associated with C3 deposition and the activation of C2, C3, C4, and C5 components. Interestingly, NDV grown in mammalian cell lines was resistant to complement neutralization by NHS. To confirm whether the incorporation of regulators of complement activity (RCA) into the viral envelope afforded complement resistance, we grew NDV in CHO cells stably transfected with CD46 or HeLa cells, which strongly express CD46 and CD55. NDV grown in RCA-expressing cells was resistant to complement by incorporating CD46 and CD55 on virions. Mammalian CD46 and CD55 molecules on virions exhibited homologous restriction, since chicken sera devoid of neutralizing antibodies to NDV were able to effectively neutralize these virions. The incorporation of chicken RCA into NDV produced in embryonated eggs similarly provided species specificity toward chicken sera.     

Complement facilitates early prion pathogenesis

New-variant Creutzfeldt-Jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs. In mouse scrapie, depletion of B-lymphocytes prevents neuropathogenesis after intraperitoneal inoculation, probably due to impaired lymphotoxin-dependent maturation of follicular dendritic cells (FDCs), which are a major extracerebral prion reservoir. FDCs trap immune complexes with Fc-gamma receptors and C3d/C4b-opsonized antigens with CD21/CD35 complement receptors. We examined whether these mechanisms participate in peripheral prion pathogenesis. Depletion of circulating immunoglobulins or of individual Fc-gamma receptors had no effect on scrapie pathogenesis if B-cell maturation was unaffected. However, mice deficient in C3, C1q, Bf/C2, combinations thereof or complement receptors were partially or fully protected against spongiform encephalopathy upon intraperitoneal exposure to limiting amounts of prions. Splenic accumulation of prion infectivity and PrPSc was delayed, indicating that activation of specific complement components is involved in the initial trapping of prions in lymphoreticular organs early after infection.     

Complement receptors in HIV infection

Similar to other pathogens, HIV can directly activate the complement pathway even in the absence of antibodies. During and after seroconversion, HIV-specific antibodies enhance the activation of complement and increase deposition of complement fragments on virions dramatically. However, even in the presence of HIV-specific antibodies, no or only poor lysis occurs. HIV has adapted different protection mechanisms to keep complement activation under the threshold necessary to induce virolysis. In addition to its own envelope proteins, the viral envelope contains membrane-anchored host molecules. Among those are complement regulatory proteins that remain functionally active on the surface of HIV and turn down the complement cascade. In addition, serum proteins with complement regulatory activities become secondarily attached onto the virus, thereby enhancing the protection of HIV against complement-mediated damage. Therefore, opsonised virions accumulate in HIV-infected individuals, which subsequently interact with complement receptor (CR) expressing cells. This review is mainly focused on these interactions, which result either in infection of CR-positive cells with high efficiency, or retention of viral particles on their surface via CRs, thereby promoting transmission of virus to other permissive cells.     

Complement components and their autoantibodies

The purpose of the immune system is to defend the host from constantly changing microbial pathogens. Autoimmune diseases develop as a consequence of the production of antibodies and/or cells that react with self-antigens, and may recruit other effector mechanisms that result in tissue damage. Thus, in this context, autoimmunity represents an immune response to self-antigens that is sufficient to cause disease. This article is specifically devoted to autoantibodies directed against complement components.     

Alternative Complement Pathway in Schizophrenia

In the present study, we evaluated functional activity of the alternative pathway of complement in schizophrenia by measuring the alternative pathway hemolytic activity (AH50) of complement as well as hemolytic activity of the complement C3 component (C3H50) in the blood of patients with schizophrenia and healthy subjects. To assess the influence of neuroleptic treatment on measured parameters, both drug-free and medicated patients were examined. In addition, correlation analysis between AH50 and C3H50 has been performed. The results of the present study clearly demonstrate upregulation of the alternative complement cascade in schizophrenia and activator effect of neuroleptics on complement alternative pathway. Based upon the results obtained we hypothesize that hyperactivation of the alternative complement pathway in schizophrenia is stimulated by apoptotic cells.