From the Guidelines
The complement cascade is a complex immune response that involves the sequential activation of over 30 proteins to eliminate pathogens from the body. This cascade can be activated through three main pathways: classical, alternative, and lectin, which converge to form C3 convertase, leading to the formation of the membrane attack complex (MAC) that causes cell lysis and death [@\1@].
Key Components of the Complement Cascade
- The classical pathway is triggered by antibody-antigen complexes
- The alternative pathway is activated by direct recognition of pathogen surfaces
- The lectin pathway is initiated by mannose-binding lectin attaching to carbohydrates on microbial surfaces
Functions of the Complement Cascade
- Direct killing of pathogens through the formation of the MAC
- Enhancement of phagocytosis through opsonization
- Recruitment of immune cells via inflammatory mediators
- Clearance of immune complexes
Clinical Significance of the Complement Cascade
- Dysregulation of the complement system is associated with various diseases, including autoimmune disorders and inflammatory conditions
- Complement deficiencies can present with systemic autoimmune disease or recurrent respiratory tract bacterial infections
- Antibiotic prophylaxis and immunization can be applied for recurrent infections in patients with complement deficiency [@\1@].
Importance of the Complement Cascade in Immune Response
- The complement system represents a critical bridge between innate and adaptive immunity
- Provides immediate defense while enhancing subsequent immune responses
- Plays a crucial role in the elimination of pathogens from the body [@\1@].
From the Research
Definition and Role of the Complement Cascade
- The complement system is a critical part of the innate immune defense, playing a major role in shaping the adaptive immune response 1.
- It is involved in several physiological processes, including tissue regeneration and clearance of immune complexes and dead cells 1.
- The complement cascade is a multi-functional system representing the first line host defense against pathogens in innate immune response, through three different pathways 2.
Pathophysiology and Clinical Implications
- Impairment of the complement system's function, consisting in deficiency or excessive deregulated activation, may lead to severe systemic infections or autoimmune disorders 2.
- The complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response 3.
- Dysregulation of the complement cascade leads to chronic inflammation, persistent pain, and neural dysfunction in various pathologies 4.
Interaction with Other Systems and Pathways
- There is a bidirectional link between the complement cascade and Neutrophil Extracellular Traps (NETs), with complement components and NETs having a significant role in the pathogenesis of several diseases characterized by inflammation 5.
- Complement signaling is particularly important in directing neuronal responses to tissue injury, neurotrauma, and nerve lesions, and regulates neuronal excitability and synaptic plasticity in the nociceptive pathways involved in pain processing 4.
Key Components and Activation Products
- C1q, the initial recognition component of the classical complement pathway, has distinct roles that are independent of the rest of the complement cascade 3.
- Complement components and relative fragments represent a key link with the humoral immune response, and have a significant role in the pathogenesis of several diseases characterized by inflammation 5.