Complement mediated lysis is an immune defense mechanism where specialized proteins work together to eliminate harmful invaders or damaged cells. This process ensures the rapid removal of threats, helping maintain health and prevent the spread of infection or cellular debris.
Understanding the Complement System
The complement system consists of numerous proteins circulating in the blood and other body fluids. These proteins do not directly attack pathogens but instead activate in a precise sequence, forming a cascade. This system functions as a major component of the innate immune system, providing a rapid, first-line defense against various threats.
Beyond directly destroying cells, the complement system performs other protective roles. It marks foreign particles or damaged cells for destruction, a process known as opsonization, making them easily recognized and engulfed by immune cells like phagocytes. The system also generates fragments that attract other immune cells to the site of infection or injury, a process called chemotaxis.
Triggering Complement Activation
The complement system activates through three distinct pathways, each initiated by different triggers. The classical pathway begins when complement proteins encounter antibody-antigen complexes on a pathogen’s surface. The C1 complex (C1q, C1r, C1s) binds to antibodies or certain microbial components. This binding activates C1r and C1s, initiating a cascade that forms a C3 convertase.
The lectin pathway is activated when circulating proteins called mannose-binding lectin (MBL) or ficolins recognize and bind to specific sugar structures, such as mannose, found on the surface of various microbes. This binding event recruits MBL-associated serine proteases (MASPs), which then activate downstream complement proteins. This pathway provides a rapid, antibody-independent defense against a broad range of pathogens.
The alternative pathway operates continuously at a low level through spontaneous hydrolysis of the C3 protein in the blood. This “tick over” mechanism generates an unstable C3b molecule, which can then bind to microbial surfaces. If C3b binds to a pathogen, it is stabilized and recruits Factor B and Factor D, leading to the formation of an alternative pathway C3 convertase. This pathway offers an immediate, antibody-independent defense, constantly surveying for foreign or abnormal surfaces.
How Cells Are Destroyed
Regardless of the activation pathway, all three converge on a common terminal sequence that leads to cell destruction. The formation of C3 convertase is a central step, as it cleaves C3 into C3a and C3b. C3b molecules then coat the target cell surface and can further contribute to the formation of C5 convertase.
This C5 convertase then cleaves C5 into C5a and C5b. C5b initiates the assembly of the Membrane Attack Complex (MAC), which is the direct effector of cell lysis. C5b first binds to the cell membrane and then recruits C6, C7, C8, and multiple copies of C9 proteins.
The C9 proteins polymerize to form a pore-like structure that inserts into the target cell’s membrane. This creates a transmembrane channel through which water, ions, and small molecules can freely pass. The uncontrolled influx of water into the cell causes it to swell and eventually burst, a process known as osmotic lysis, destroying the invader.
Complement’s Impact on Health
The complement system plays an important role in protecting the body from infections and maintaining tissue health. Its ability to directly lyse bacteria is a strong defense mechanism. It also aids in clearing immune complexes and apoptotic (dying) cells, preventing their accumulation and subsequent inflammation or autoimmune responses.
Dysregulation of the complement system can lead to health problems. Overactive complement can damage healthy host tissues, contributing to autoimmune diseases or certain kidney diseases. Conversely, deficiencies in complement proteins can increase susceptibility to recurrent bacterial infections, as the body’s ability to clear pathogens is compromised.