Opsonization（オプソニン化）とは？

Opsonization is an immunological process where pathogens are "tagged" for elimination. This mechanism relies on either antibodies or complement proteins, to bind to the surface of pathogens. This helps phagocytic cells—like macrophages and neutrophils—to recognize, engulf, and destroy the pathogens. Opsonization has various functions, including increasing the efficiency of phagocytic cells, triggering immune responses, and preventing autoimmunity.

How Opsonization Works

Opsonization occurs via two main pathways: antibody-mediated opsonization and complement system activation. Both pathways recruit phagocytic cells that ingest and digest the tagged pathogen.

1. Antibody-Mediated Opsonization

Antibodies, produced by plasma cells in response to specific antigens, bind to pathogens using their variable regions (Fab). Once bound, the constant region (Fc) of the antibody becomes accessible for interaction with Fc receptors on phagocytic cells.

• The Fc receptors on phagocytes recognize and bind to the Fc region of the antibody-coated pathogen. 

• After binding, the pathogen is engulfed into a phagosome, which fuses with lysosomes containing digestive enzymes, ultimately leading to pathogen destruction. 

• Multiple antibodies binding to various antigen sites on a pathogen improve recognition and increase the efficiency of ingestion. 

Antibody isotypes play different roles in opsonization. For instance, IgG is particularly effective due to its strong binding affinity to Fc receptors, while IgA predominantly functions in mucosal immunity. IgM, despite its size, triggers complement activation that indirectly aids in opsonization. 

2. Complement-Mediated Opsonization

The complement system consists of over 30 proteins that circulate in an inactive state. Upon pathogen detection, these proteins are activated through three pathways: classical, alternative, or lectin. The common endpoint of these pathways is the formation of C3 convertase, which cleaves inactive C3 into its active fragments, C3a and C3b. 

• C3b binds to the surface of pathogens, marking them for phagocytosis. 

• Complement receptors on macrophages or neutrophils detect C3b, facilitating pathogen uptake. 

• C3b can act alongside antibodies to amplify the opsonization process. 

Impaired Opsonization

When opsonization is disrupted, the immune system's ability to defend against infections is significantly reduced. Conditions that affect opsonization include:

• C3 Deficiency: Patients lacking functional C3 protein often suffer from recurrent respiratory and sinus infections. 

• Selective IgA Deficiency: Individuals with low IgA levels are more susceptible to gastrointestinal and respiratory infections, as IgA plays a key role in mucosal immunity. 

• Paroxysmal Nocturnal Hemoglobinuria (PNH): A defect in proteins like CD55 (Decay-Accelerating Factor) impairs the regulation of complement activity, leading to red blood cell destruction. 

Impaired opsonization also hinders the clearance of apoptotic cells, increasing the risk of autoimmune disorders.

Opsonization in Therapeutics

Opsonization is not only a natural defense mechanism but also a target for therapeutic interventions. Monoclonal antibodies designed for conditions like cancer and infectious diseases can leverage opsonization to enhance immune-mediated clearance of abnormal cells or pathogens. For example, engineered human antibodies for the opsonization and killing of Staphylococcus aureus.³ 

Related: Core Functions of Antibodies

References:

1. Rezaei, N., Sadeghalvad, M., & Mohammadi-Motlagh, H. (2022). General Concepts of Immunity. Encyclopedia of Infection and Immunity, 1-13. https://doi.org/10.1016/B978-0-12-818731-9.00043-4

2. Thau, L., Edinen Asuka, & Mahajan, K. (2023, May). Physiology, Opsonization. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK534215/

3. Chen, X., Olaf Schneewind, & Missiakas, D. (2022). Engineered human antibodies for the opsonization and killing ofStaphylococcus aureus. Proceedings of the National Academy of Sciences, 119(4). https://doi.org/10.1073/pnas.2114478119