Complement Innate SP 25 (2)

Complement System

Innate Immunity

  • Part of non-specific innate immune response

  • Involves early induced immunity

Complement: Introduction

  • What is it?: A system that enhances the ability of antibodies and phagocytic cells to clear pathogens.

  • Where is it?: Circulates in the blood in inactive forms until activated.

  • When does it work?: Activated after exposure to a pathogen via several pathways.

Complement Activation Pathways

  • Complement proteins are activated in a sequential manner, not numerically.

  • Activation pathways:

    1. Classical Pathway: Discovered first; acts last; initiated by antibodies.

    2. Alternative Pathway: Acts first; spontaneous activation.

    3. Lectin Pathway: Initiated by mannose-binding lectins recognizing pathogens.

Pathway Activation Details

  • Alternative Pathway: Pathogen surface alters environment for complement activation.

  • Lectin Pathway: Mannose-binding lectin binds to pathogen surface.

  • Classical Pathway: C-reactive protein or antibodies bind to specific antigens on pathogens.

Initial Events of Activation

  • Lectin Pathway: MBL binds carbohydrates on pathogens, activating C4 and C2.

  • Classical Pathway: C1 binds antibodies to activate C4 and C2.

  • Alternative Pathway: C3 spontaneously hydrolyzes to bind to pathogen surfaces without C4 or C2.

Merging of Pathways

  • All pathways converge to generate a C3 convertase, which cleaves C3 and binds C3b to microbial surfaces.

Classical Pathway Events

  • C1s cleaves C4 and C2, leading to the formation of the C3 convertase (C4b2a).

Functions of Complement

  1. Opsonization of Pathogens: C3b coats pathogen surfaces, aiding phagocytosis.

  2. Inflammation: Anaphylatoxins (C3a, C4a, C5a) increase vascular permeability and attract immune cells.

  3. Membrane Attack Complex (MAC): Formed by C5b, C6, C7, C8, and C9; creates pores in pathogen membranes causing lysis.

Summary of Functions of Complement

  • Lysis: Disruption of pathogen cell membranes.

  • Opsonization: Enhances phagocytosis of pathogens.

  • Activation of Inflammatory Response: Initiates and modulates inflammation.

Microbial Strategies for Complement Evasion

  • Strategies:

    • Interfering with antibody-complement interaction

    • Inactivation of complement proteins

    • Protease-mediated destruction of complement components

    • Mimicking complement regulatory components

  • Examples:

    • Staphylococcal protein A depletes antibodies.

    • S. aureus protein SCIN inhibits C3 convertase.

    • Various parasites express proteins to evade complement actions.