The Role of Cells in Complement System Activation: Exploring the Classical, Lectin, and Alternative Pathways

cells, complement activation

Cells play a vital role in the activation of the complement system

Cells play a vital role in the activation of the complement system. The complement system is a part of the immune system that helps in fighting off infections and clearing damaged cells from the body. It consists of a complex set of proteins, known as complement proteins, which interact with each other and with cells to initiate and regulate immune responses.

The activation of the complement system can occur through three main pathways: the classical pathway, the lectin pathway, and the alternative pathway. All three pathways converge at the formation of the C3 convertase enzyme, which is responsible for activating downstream complement components.

Cells are key players in the activation of the complement system through these pathways. Let’s take a closer look at each pathway and the role of cells within them:

1. Classical pathway: This pathway is primarily activated by antibody-antigen complexes. When antibodies recognize and bind to foreign substances, such as bacteria or viruses, they can activate the complement system. The Fc region of the antibody interacts with complement protein C1q, which in turn binds to C1r and C1s to form the C1 complex. This complex then cleaves complement protein C4 and C2, generating the C3 convertase enzyme, C4bC2a. This enzyme triggers the subsequent cascade of complement activation. Thus, cells that can produce antibodies, such as B lymphocytes or plasma cells, are involved in initiating the classical pathway.

2. Lectin pathway: This pathway is initiated by pattern recognition receptors (PRRs), specifically mannose-binding lectin (MBL), on cells. MBL recognizes sugar residues on the surface of pathogens or damaged cells. When MBL binds to these sugar residues, it associates with MBL-associated serine proteases (MASPs) to form an active complex. The MASPs cleave C4 and C2 to produce the C3 convertase, leading to complement activation. Therefore, cells expressing MBL, including liver cells, macrophages, and dendritic cells, play a crucial role in initiating the lectin pathway.

3. Alternative pathway: This pathway provides continuous low-grade complement activation in the absence of specific immune triggers. The alternative pathway begins with spontaneous hydrolysis of C3 into C3b. C3b can bind directly to foreign surfaces, but it is quickly regulated by complement regulatory proteins on self-cells to prevent unnecessary damage. However, if C3b binds to a target surface lacking these regulatory proteins, it can initiate the formation of the C3 convertase, C3bBb. This convertase can further cleave C3, amplifying the complement response. Cells, including neutrophils, monocytes, and macrophages, provide a surface for initial complement activation in the alternative pathway.

In summary, cells are essential for complement activation by serving as initiators or regulators of the complement system. B lymphocytes or plasma cells produce antibodies that activate the classical pathway, while cells expressing MBL, such as liver cells or macrophages, initiate the lectin pathway. Additionally, cells with surfaces that lack complement regulatory proteins, like neutrophils or monocytes, provide the platform for initial complement activation in the alternative pathway. By engaging cells, the complement system can effectively identify and eliminate pathogens and damaged cells, contributing to the immune response.

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