Imprime PGG-Mediated Anti-Cancer Immune Activation Requires Immune Complex Formation

Imprime PGG (Imprime), an intravenously-administered, soluble β-glucan, has shown compelling efficacy in multiple phase 2 clinical trials with tumor targeting or anti-angiogenic antibodies. Mechanistically, Imprime acts as pathogen-associated molecular pattern (PAMP) directly activating innate immune effector cells, triggering a coordinated anti-cancer immune response. Herein, using whole blood from healthy human subjects, we show that Imprime-induced anti-cancer functionality is dependent on immune complex formation with naturally-occurring, anti-β glucan antibodies (ABA). The formation of Imprime-ABA complexes activates complement, primarily via the classical complement pathway, and is opsonized by iC3b. Immune complex binding depends upon Complement Receptor 3 and Fcg Receptor IIa, eliciting phenotypic activation of, and enhanced chemokine production by, neutrophils and monocytes, enabling these effector cells to kill antibody-opsonized tumor cells via the generation of reactive oxygen species and antibody-dependent cellular phagocytosis. Importantly, these innate immune cell changes were not evident in subjects with low ABA levels but could be rescued with exogenous ABA supplementation. Together, these data indicate that pre-existing ABA are essential for Imprime-mediated anti-cancer immune activation and suggest that pre-treatment ABA levels may provide a plausible patient selection biomarker to delineate patients most likely to benefit from Imprime-based therapy.     

肝脏固有免疫系统对肠源性感染的免疫应答与免疫耐受机制

肝特殊的解剖结构及生理特征使其成为暴露肠源性抗原的主要器官。由于肝具有独特的固有免疫系统,在正常情况下,肝分布多种致耐受的抗原提呈细胞,对持续性表达或递呈于肝的肠源性抗原物质,诱发针对该抗原的系统性免疫耐受,避免肝受到不必要的免疫损伤。当炎症发生及肝脏固有免疫系统活化时,则通过免疫效应细胞及免疫效应因子对肠源性病原体发挥强烈地免疫应答以控制感染。该过程形成机制的研究对肝功能的理解及肝性疾病的预防与治疗至关重要。本文就肝固有免疫系统对肠源性感染的免疫应答与免疫耐受形成机制作一综述。     

RNAi-分子免疫系统

RNA干扰(RNA interference,RNAi)或RNA沉默是广泛存在于从植物到哺乳动物的真核生物体中小RNA诱导的基因沉默机制.该领域新的研究进展清楚表明在植物和动物中KNAi起着天然抗病毒作用.因此,KNAi常被视为有效的分子免疫系统.深入理解该分子免疫系统非常有助于揭示一些病毒病的致病机制和开发有效的抗病毒疗法.因此,就该分子免疫系统的研究进展作以综述.     

Immune system physiology

Processes of interaction of immunocytes of different origin and with different cytokins, underlie the immune system mechanisms. The immune system structure, lymphocytes variety and properties, molecular basis of antigen recognition, were described. Dynamic structure of peripheral part of the immune system, immunocytes migration and re-circulation role in integration of lymphoid organs, were demonstrated. The molecular and cellular basis of the immune reaction and immune memory, were discussed.     

Rifampicin-induced Immune Thrombocytopenia

A case is reported in which severe thrombocytopenia occurred during administration and readministration of rifampicin. The patient''s erythrocytes gave a positive direct antiglobulin test due to complement on the red cell surface; in the serum, complement-fixing antibodies were detected which were directed against the drug.Immunological studies showed antibodies, of both IgG and IgM type, capable of fixing complement to both normal and the patient''s platelets, but only in the presence of rifampicin. In addition the IgM type of antibody (but not the IgG) was capable of fixing complement to normal red cells; again only in the presence of the drug.     

流感病毒先天免疫应答和先天免疫逃逸的机制

流感病毒引起人类和动物的呼吸道感染已是全世界严重的经济和公共卫生问题。在感染早期,流感病毒会导致机体的先天免疫信号被激活,起到防御、清除病毒以及辅助适应性免疫应答的作用。但在与宿主共进化的过程中,流感病毒形成了多种逃逸策略,主要是通过病毒自身蛋白质阻断宿主天然免疫通路,抑制干扰素和炎性因子的生成。基于现有的研究成果,本文针对流感病毒先天免疫应答和先天免疫逃逸的机制做一扼要综述,这有助于加强流感病毒抗原进化的监测、探索疫苗和抗病毒药物的合理靶标,为更好地预防和控制该病提供有效的策略。     

Immune Response Suppression by an Inhibitor in Normal and Immune Mouse Serum

CONTROL mechanisms responsible for determining the intensity and duration of the immune response have been studied extensively. Jerne¹ and Uhr and Möller² described the phenomenon of feedback inhibition whereby the production of a 7S class of antibodies terminates the formation of antibodies with the same specificity. An immunosuppressive effect has also been observed in antigenic competition, in which the administration of one antigen results in a reduced response to a subsequently administered second antigen³. Recently, several investigations have focused on the mechanism of antigenic competition^4,5. A humoral rather than cellular mechanism is generally believed to be responsible for this phenomenon^4–6, but attempts to identify the humoral mediator have been unsuccessful. We have also searched for a humoral substance responsible for the immunosuppressive effect in antigenic competition and found in the sera of adult untreated mice an immunosuppressive agent whose concentration was substantially increased after antigenic stimulation.     

植物NLR免疫受体的识别、免疫激活与信号调控

高等植物进化出大量膜表面和胞内免疫受体以感知各种病原信号,抵御病原物入侵。其中,细胞表面的模式识别受体感知模式分子后激活基础免疫反应,核苷酸结合和富亮氨酸重复蛋白(NLRs)则通过感知病原微生物分泌的效应蛋白激活特异免疫反应,导致超敏反应与细胞死亡。该文主要综述了NLRs对效应蛋白的识别、植物免疫激活及下游信号调控的最新研究进展。     

Immune complexes in cancer

Conclusion It is clear that a wide variety of methods for measuring immune complexes are available but some may have disadvantages, such as technical difficulty, and all suffer from a lack of satisfactory standardization (WHO, 1977). However, in spite of these difficulties, the measurement of immune complexes may itself prove useful in monitoring of patients, and the complexes may provide a route to the identification and isolation of tumor related products, which would allow a more direct quantitation of tumor burden.     

Immune carriers of cytostatics

Summary Chemotherapeutic drugs lack specificity for tumor cells. The specific antitumor action can be acquired by the use of drug-carrying antibodies with specific affinity for tumor cells.Some aspects of this form of immunochemotherapy, such as (a) the antitumor antibody preparation, (b) the effect of the coupling of the drug to the antibody on both the drug and the antibody activity, and (c) future possibilities, are discussed in relation with recent animal and clinical studies.