Complement System and Its Biological Effects

Complement System: Biological Consequences

• The complement system plays a crucial role in the innate immune response.
• Complement activation leads to pathogen elimination through various mechanisms.

Biological Consequences of Complement Activation

• Amplifies humoral response: Complement enhances the effectiveness of antibody-mediated defenses.
• Lyses cells: The membrane attack complex (MAC) directly destroys pathogen cell membranes.
• Inflammatory response: Complement components trigger inflammation, attracting immune cells to the site of infection.
• Opsonisation: Complement proteins (e.g., C3b, C4b) coat pathogens, making them more readily recognized and engulfed by phagocytic cells.
• Clearance of immune complexes: Complement helps remove immune complexes from circulation to prevent tissue damage.

Cell Lysis

• MAC targets a broad spectrum of cells: The MAC is effective against a wide range of pathogens involved in infections.
• Gram-positive bacteria resistance: Gram-positive bacteria often have thicker cell walls (peptidoglycan), offering protection against MAC formation.
• Evasion mechanisms: Certain pathogens have evolved strategies to evade complement-mediated killing.

Microbial Evasion of Complement-Mediated Damage

• Some pathogens have mechanisms to obstruct the complement cascade, such as altering the composition of their cell walls to prevent MAC insertion or producing enzymes that inactivate complement components.
• Details of mechanisms by which specific pathogens can limit complement activation are listed.

Mediating Inflammation

• Anaphylatoxins: Complement components (e.g., C3a, C5a) activate mast cells and basophils, resulting in inflammation.
• Vascular permeability: Complement activation enhances the permeability of blood vessels to allow immune cells to enter the infected tissue.
• Chemotaxis: Complement components attract immune cells to the site of infection.

Opsonisation

• C3b and C4b mediate phagocytosis: These complement components act as opsonins, enhancing phagocytosis by macrophages and neutrophils.
• Phagocytosis is a critical process of removing pathogens to limit infection and inflammation.

Viral Neutralization

• Complement activation can neutralize viruses by interfering with their ability to infect cells.
• The mechanisms range from binding to viral surfaces to lysing virus-infected cells.
• This helps prevent the spread of viral infections and reduce the potential for viral replication.

Clearing of Immune Complexes

• Immune complex buildup: Accumulation of immune complexes can trigger tissue damage.
• C3b coating of complexes: C3b coats harmful immune complexes.
• Removal by RBCs: Red blood cells assist in transporting and removing immune complexes to prevent harm.
• Liver and spleen clearance: The liver and spleen filter and remove immune complexes from the blood.
• Complement deficiency: Deficiencies in complement proteins can impair the clearance of immune complexes, potentially leading to complications.

Complement Receptors

• Complement receptors mediate complement effector mechanisms: These receptors on immune cells recognize and bind to complement-coated pathogens.
• Types of receptors are identified and their specific roles are described.

Summary

• The activated complement system significantly boosts the immune response.
• Direct cell death occurs by forming a MAC.
• Inflammation is induced to attract immune cells to infection sites.
• These mechanisms collectively strengthen the immune system's ability to eliminate pathogens and maintain homeostasis.