Complement System

The complement system is a sophisticated part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promotes inflammation, and attacks the pathogen's cell membrane. This system is named for its capacity to "complement" the killing of pathogens by antibodies.

Comprising over 30 small proteins produced by the liver, the complement system circulates in the blood serum and within tissues throughout the body. These proteins are normally inactive but become sequentially activated in response to a pathogen. Activation can occur via three pathways: the classical pathway, which is triggered by antibodies bound to a pathogen; the lectin pathway, which is activated by mannose-binding lectin attaching to the pathogen surface; and the alternative pathway, which can be initiated directly by pathogen surfaces.

Each pathway leads to the cleavage of the protein C3, generating C3a and C3b fragments. C3b binds to the pathogen surface and can lead to direct opsonization—tagging the pathogen for destruction by phagocytes. C3a, along with other small fragments released during complement activation, acts as a chemoattractant to recruit immune cells to the site of infection and promote inflammation.

The final common step of the complement activation pathways is the assembly of the membrane attack complex (MAC). This complex forms a pore in the membrane of the target cell, leading to cell lysis and death. The MAC is particularly effective against gram-negative bacteria.

Regulation of the complement system is crucial, as overactivation can damage host cells. Regulators are present in blood plasma and on cell surfaces, ensuring the system is directed only at pathogens or damaged cells.

The complement system plays a crucial role not only in innate immunity but also as a bridge to adaptive immunity. It assists in clearing immune complexes and apoptotic cells, and in enhancing the humoral response and immune memory.

Understanding and manipulating the complement system has therapeutic potential for numerous diseases, including those that involve excessive or inappropriate activation of the complement pathways.

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  2. glucocorticoid receptor agonist

    地塞米松是一种强效的合成糖皮质激素类固醇药物。它具有抗炎和免疫抑制作用。其效力约为天然激素氢化可的松的20-30倍,以及强的松的4-5倍。
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  4. Rosmarinic acid 是从唇形科草本植物中分离出的一种苯丙烷类化合物。
  5. glucocorticoid receptor agonist

    Dexamethasone acetate (Dexamethasone 21-acetate) is a glucocorticoid receptor agonist.
  6. C5a receptor antagonist

    PMX-205 是一种环状六肽,作为 C5a 受体(C5aR; IC50 = 31 nM)的强效拮抗剂。
  7. glucocorticoid receptor agonist

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  8. glucocorticoid receptor agonist

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  9. Factor D inhibitor

    Danicopan(ACH-4471),一种选择性且口服活性的小分子因子D抑制剂,对人类因子D具有高结合亲和力,Kd值为0.54 nM。
  10. C5 inhibitor

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  11. Factor B inhibitor

    LNP023 是一种高效的因子 B(FB)抑制剂,其 IC50 值为 10 nM。LNP023 显示出对人类 FB 的直接、可逆和高亲和力结合(KD=7.9 nM)。
  12. factor d inhibitor

    Complement factor D-IN-1 是一种高效且选择性的小分子可逆 因子 D 抑制剂,在 FD Thioesterolytic Fluorescent Assay 中的 IC50 为 0.006 μM,在 MAC Deposition Assay 中的 IC50 为 0.05 μM。
  13. C3a receptor antagonist

    SB290157 trifluoroacetate 是一种强效且选择性的 C3a 受体拮抗剂,其 IC50 为 200 nM。
  14. Primates' C3 Inhibitor

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    POT-4(AL-78898A),一种Compstatin衍生物,是一种强效的补体因子C3激活抑制剂。POT-4可用于年龄相关性黄斑变性研究。

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