Classical pathway

Classical Pathway is a component of the immune system specifically involved in the complement system, which is a part of the innate immunity. The classical pathway is one of the three pathways that activate the complement system, the other two being the lectin pathway and the alternative pathway. The primary function of the classical pathway is to bind antibodies that are attached to pathogens or pathogen-infected cells, leading to the activation of the complement system and subsequent destruction of the pathogens.

Activation

The classical pathway is activated when C1-complex (a molecule part of the complement system, composed of C1q, C1r, and C1s) binds to the Fc region of an antibody that has itself bound to an antigen on the surface of a pathogen. This interaction requires the presence of at least two IgG antibodies or one IgM antibody, which changes its shape upon binding to an antigen, exposing a site that can bind to C1q and initiate the complement activation.

Components

The key components of the classical pathway include:

• C1 Complex: Initiates the classical pathway activation. It is a complex of C1q, C1r, and C1s proteins.
• C4: Upon activation by C1s, it is cleaved into C4a and C4b.
• C2: C4b binds to C2, allowing it to be cleaved by C1s into C2a and C2b.
• C3 Convertase: The combination of C4b and C2a forms the C3 convertase of the classical pathway, which cleaves C3 into C3a and C3b, propagating the complement activation.

Functions

The activation of the classical pathway leads to several key functions in the immune response, including:

• Opsonization: Marking pathogens for destruction by phagocytes.
• Cell Lysis: Formation of the Membrane Attack Complex (MAC) that creates pores in the cell membranes of pathogens, leading to their lysis.
• Inflammation: Anaphylatoxins (C3a, C4a, and C5a) generated during complement activation promote inflammation, attracting immune cells to the site of infection.

Regulation

The classical pathway is tightly regulated to prevent damage to host cells. Regulatory proteins such as C1-inhibitor, which inhibits the C1 complex, and Factor H and Factor I, which prevent the formation of the C3 convertase, play crucial roles in preventing the complement system from attacking host cells.

Clinical Significance

Dysregulation or deficiencies in the components of the classical pathway can lead to various diseases, including autoimmune diseases, where the immune system attacks the body's own cells, and immunodeficiency diseases, where the immune response is inadequate to protect against infections. Therapeutic interventions targeting the classical pathway are being explored for treating these conditions.