Complement system: Components, nomenclature and complement activation pathway.

The complement system is a complex and important component of the innate immune system. It consists of a series of proteins and protein complexes that work together to help eliminate pathogens, clear immune complexes, and mediate various immune responses. The complement system is named for its ability to complement or enhance the immune system's other defense mechanisms. Here, I'll outline the components, nomenclature, and the main complement activation pathway, known as the classical pathway:

Components of the Complement System: The complement system includes various proteins, most of which are designated with the prefix "C" followed by a number. Some of the key components include:

1. C1-C9: These are the core complement proteins involved in various activation pathways.

2. Complement Receptors: These are present on immune cells and recognize complement-coated pathogens, helping to facilitate their clearance.

3. Regulatory Proteins: These proteins help prevent excessive complement activation on host cells and tissues to avoid self-damage.

4. Anaphylatoxins: These are small complement fragments generated during activation and can induce inflammation.

Nomenclature: Complement proteins are typically named using the C-number system, and they often exist in multiple forms (e.g., C3, C3a, C3b). Here's a brief explanation:

• C1, C2, C3, C4, C5, C6, C7, C8, C9: Core complement proteins involved in activation.
• C3a and C5a: Anaphylatoxins that promote inflammation.
• C3b and C4b: Opsonins that tag pathogens for phagocytosis.
• C1q, C1r, and C1s: Components of the C1 complex in the classical pathway.
• Factor B, Factor D, Properdin (P), and Factor H: Proteins involved in the alternative pathway.
• Mannose-Binding Lectin (MBL): Initiates the lectin pathway.
• CD59 and CD55 (DAF - Decay-Accelerating Factor): Regulatory proteins that protect host cells from complement attack.

Classical Complement Activation Pathway: The classical pathway is one of the three main activation pathways of the complement system and is typically initiated by the binding of antibodies to pathogens. Here's a simplified overview of the classical pathway:

1. Recognition: Antibodies (e.g., IgG or IgM) are produced by the adaptive immune system in response to infection. These antibodies can bind to specific antigens on the surface of pathogens.

2. C1 Activation: The first component of the classical pathway is C1, which is a complex consisting of C1q, C1r, and C1s. C1q binds to the Fc region of antibodies that have bound to pathogens, leading to C1 activation.

3. Cleavage Cascade: Once activated, C1r and C1s enzymatically activate other complement proteins (C4 and C2) through a proteolytic cascade. C4 is cleaved into C4a and C4b, while C2 is cleaved into C2a and C2b.

4. Formation of C3 Convertase: C4b and C2a come together to form the C3 convertase, which can cleave C3 into C3a and C3b.

5. Opsonization and Membrane Attack Complex (MAC) Formation: C3b is an opsonin that tags pathogens for phagocytosis by immune cells. Additionally, multiple C3b molecules can participate in the formation of the MAC, which creates pores in the pathogen's membrane, ultimately leading to cell lysis.

6. Anaphylatoxin Release: C3a and C5a, generated during the process, serve as anaphylatoxins that trigger inflammation by attracting immune cells and increasing vascular permeability.

The classical pathway is an important means of complement activation, and it coordinates with the other pathways (alternative and lectin pathways) to provide robust protection against pathogens. The complement system plays a critical role in immune defense, inflammation, and tissue homeostasis.