positive regulation of complement activation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of complement activation. [GOC:go_curators]

Positive regulation of complement activation is a crucial process in the innate immune response, designed to eliminate pathogens and damaged cells. This process is tightly regulated to prevent excessive inflammation and tissue damage. The complement system is a cascade of proteins in the blood that, when activated, leads to the formation of a membrane attack complex (MAC) which can lyse target cells.

Positive regulation of complement activation involves several key steps:

1. **Initiation:** The complement system can be activated through three main pathways: the classical, lectin, and alternative pathways. The classical pathway is triggered by the binding of antibodies to antigens on the surface of pathogens or damaged cells, while the lectin pathway is activated by the binding of lectins to mannose residues on pathogens. The alternative pathway is a spontaneous activation pathway that is continuously active at low levels.

2. **Amplification:** Once initiated, the complement cascade is amplified by the activation of C3 convertase, an enzyme complex that cleaves C3 into C3a and C3b. C3b binds to the pathogen surface and acts as an opsonin, facilitating phagocytosis by immune cells.

3. **Formation of C5 convertase:** C3b further binds to the C3 convertase, creating the C5 convertase, another enzyme complex. This enzyme then cleaves C5 into C5a and C5b.

4. **MAC formation:** C5b initiates the assembly of the MAC, a pore-forming complex that inserts into the cell membrane of the target cell, leading to cell lysis.

5. **Regulation:** The complement cascade is tightly regulated by a series of regulatory proteins that prevent excessive activation and damage to host cells. These proteins include C1 inhibitor, factor H, factor I, and membrane cofactor protein (MCP).

Positive regulation of complement activation involves the enhancement or acceleration of these steps. This can be achieved through various mechanisms:

* **Increased production of complement proteins:** Immune cells can produce and release more complement proteins, boosting the availability of components for the cascade.
* **Enhanced binding of complement proteins:** Antibodies, lectins, and other factors can promote the binding of complement proteins to their targets, facilitating activation.
* **Increased enzymatic activity:** Factors like properdin can stabilize the C3 convertase, leading to amplified activation.
* **Reduced activity of complement inhibitors:** Immune cells can suppress the activity of regulatory proteins like factor H, allowing the cascade to proceed more effectively.

These positive regulatory mechanisms ensure a robust and efficient complement response against pathogens, ultimately contributing to the elimination of threats and the maintenance of host health.'
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Proteins (1)

Compounds (2)