Immunology Lecture - The Complement System

Overview of the Lecture

• Lecture number five focused on the innate immune system.

• Professor Georges Grauen will give subsequent lectures about MHC antigen presentation.

• Following sessions will cover B cells and T cells.

• Celebration of National Immune System Day on March 11, 2025.

• Reminder about the early feedback task due on March 16 by 11:59 PM.

The Complement System

• Definition: The complement system is a collection of soluble proteins produced mainly by the liver that assists the innate immune system.

• Function: Complements help in antimicrobial activity and activate immune cells (neutrophils, leukocytes, macrophages).

• Activation: The complement system can be activated via three pathways:

  • Alternative pathway

  • Classical pathway

  • Mannose-binding lectin (lectin) pathway

• Mechanism of Activation: Activation involves proteolytic cleavage, converting inactive complement proteins to active forms (e.g., C3).

Pathways of Activation

1. Alternative Pathway

• C3 Tick Over: Constant low-level breakdown of C3 in the blood; activates upon contact with microbes.

  • C3 converts to C3B (opsin) and C3A (inflammatory).

• Formation of C5 Convertase: C3B binds to the microbial surface, stabilizing further complex formation leading to C5 activation (C5B and C5A).

2. Classical Pathway

• Trigger: Initiated by antibodies, primarily IgM and subclasses of IgG (IgG1 and IgG3) that bind to pathogens.

• C1 Complex: Binds to Ig, activating proteolytic cleaving of C4.

• Formation of C3 Convertase: Specific binding allows formation of C4B2A, which cleaves C3 to produce C3B and C3A, leading to C5 convertase activation.

3. Mannose-Binding Lectin Pathway

• Mechanism: Similar to classical, but uses mannose-binding lectin instead of antibodies.

• Activation: Binds to specific sugars on pathogens, activating serine proteases (MASP1 and MASP2) to cleave complement proteins downstream.

Common Late Steps of All Pathways

• All pathways converge to form C5 convertase leading to:

  • C5B: Component that inserts into membranes to form the membrane attack complex (MAC).

  • C3A and C5A: Act as chemokines to recruit immune cells, causing inflammation.

• Membrane Attack Complex (MAC): Formed by incorporating C5B, C6, C7, C8, and multiple C9 molecules, disrupting the pathogen's membrane, resulting in cell lysis.

Functions of Complement Components

• C3B: Opsinizes pathogens for phagocytosis, enhances immune response.

• C3A and C5A: Serve as inflammatory mediators to recruit immune cells.

• Regulatory Mechanisms: Prevent complement action against self-cells, ensuring specificity in targeting pathogens.

Disorders Related to Complement System

• C3 Deficiency: Inability to produce key complement components, leading to increased susceptibility to infections.

• C2 Deficiency: Impairs classical pathway functions, associated with autoimmune conditions like lupus.

• Regulatory Deficiencies: Lack of inhibitors (e.g., C1 inhibit) leads to uncontrolled activation and damage to host tissues leading to issues such as edema.

Conclusion and Final Remarks

• The complement system is crucial for immediate immune responses, alongside other systems.

• Next lectures will focus on adaptive immunity, presenting deeper insights into cell-mediated responses and MHC presentation.