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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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  1. A10260
    Cyclosporin A

    Cyclosporin A (Cyclosporine A) is an immunosuppressant agent widely used in post-allogeneic organ transplant to reduce the activity of the immune system.
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  2. A10299
    Dexamethasone

    Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant. Its potency is about 20-30 times that of the naturally occurring hormone hydrocortisone and 4-5 times of prednisone.
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  3. A13968
    Leukadherin 1

    Integrin agonist

    Leukadherin 1 is an allosteric activator of CD11b/CD18. Increases CD11b/CD18-dependent cell adhesion to fibrinogen (EC50 = 4 μM).
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  4. A14555
    Rosmarinic acid

    Rosmarinic acid is a phenylpropanoid isolated from Labiatae herbs.
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  5. A16494
    Dexamethasone acetate

    glucocorticoid receptor agonist

    Dexamethasone acetate (Dexamethasone 21-acetate) is a glucocorticoid receptor agonist.
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  6. A17080
    Dexamethasone Phosphate disodium

    Dexamethasone Phosphate disodium is a is a water-soluble form of the synthetic glucocorticoid dexamethasone.
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  7. A18453
    Dexamethasone palmitate

    Dexamethasone palmitate (DXP) is a prodrug of Dexamethasone, which is a glucocorticoid receptor agonist. Dexamethasone palmitate (DXP) has a 47-fold lower affinity for the glucocorticoid receptor than Dexamethasone. Anti-inflammatory agent.
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  8. A18609
    Danicopan

    Factor D inhibitor

    Danicopan (ACH-4471), a selective and orally active small-molecule factor D inhibitor, shows high binding affinity to human Factor D with Kd value of 0.54 nM.
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  9. A21347
    SB290157 trifluoroacetate

    C3a receptor antagonist

    SB290157 trifluoroacetate is a potent and selective C3a receptor antagonist with an IC50 of 200 nM.
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