Opsonization refers to the capacity of antibodies and complement components, along with other proteins, to coat harmful antigens.
Once coated, these antigens can be recognized by antibodies or complement receptors present on phagocytic cells.
It is a molecular mechanism in which molecules, microbes, or apoptotic cells are chemically modified.
This modification strengthens their interaction with cell surface receptors on phagocytes and antibodies.
The process serves as a mechanism for identifying invading particles (antigens) through the involvement of specific components known as opsonins.
Opsonins function as markers or tags that enable the immune system of the body to recognize these antigens.
An opsonin is defined as any molecule that enhances phagocytosis by either marking an antigen for an immune response or marking dead cells for recycling.
The overall purpose of opsonization is to make antigens more palatable and easily recognizable to antibodies or phagocytic cells.
Mechanism of Opsonization
Opsonization of pathogens can occur either through antibodies or the complement system.
The mechanism of opsonization is employed by antibodies to inhibit infections and facilitate their clearance from the body.
Antibody-mediated opsonization involves the coating of pathogens with antibodies, making them recognizable and phagocytosed by innate immune cells.
Encapsulated bacteria that typically resist phagocytosis become highly attractive to neutrophils and macrophages once coated with antibodies, leading to a significantly enhanced rate of clearance from the bloodstream.
Research into the structure of immunoglobulins revealed that IgG is the heat-stable serum factor responsible for antigen-specific opsonization.
IgG binds to antigens via its two antigen-binding fragments (Fab), which attach to antigenic determinants located on the surface of microorganisms or other particles.
Once IgG combines with an antigen, the IgG molecule undergoes specific conformational and configurational changes in the F(ab)2 hinge region.
Phagocytic cells of all types possess receptors for IgG molecules on their plasma membranes.
The number of these receptors on each mouse peritoneal and alveolar macrophage is estimated to be between 1–2 million.
These receptors are resistant to tryptic proteolysis and can mediate binding of IgG-coated particles at both 4°C and 37°C, even in the absence of divalent cations.
Although all four subclasses of human IgG can bind to antigens, only IgG1 and IgG3 are capable of binding to receptors on phagocytic cells.
The receptors on phagocytic cells bind exclusively to the Fc portion of IgG molecules and are therefore termed Fc receptors.
In antibody-mediated opsonization, when pathogen–antibody complexes bind to Fc receptors on phagocytes, this induces internalization of the complex.
Once internalized, the pathogen is digested inside lysosomes.
Typically, multiple antibodies attach to different antigenic sites on a pathogen, which increases both the efficiency and likelihood of phagocytosis and subsequent destruction within phagosomes and lysosomes.
Complement-mediated Opsonization
The complement system consists of more than 30 proteins that enhance the ability of antibodies and phagocytic cells to fight invading organisms.
This system initiates phagocytosis by opsonizing antigens and also plays a role in enhancing inflammation and causing cytolysis.
The most critical heat-labile opsonin, and perhaps the most essential opsonin overall, is C3b.
C3b is generated when the complement component C3 is cleaved by a C3-convertase, producing fragments C3a and C3b.
The cleavage of C3 can occur through two main pathways:
Classical pathway: initiated by the binding of IgG or IgM molecules to antigens, which leads to activation of the C1 complex.
Alternative pathway: initiated directly by lipid–carbohydrate complexes present in bacterial cell walls.
After cleavage, C3b binds to the surface of particles and acts as an opsonin.
Once coated with C3b, a particle must be recognized and bound by the surface of a phagocytic cell before ingestion can occur.
Studies show that all mononuclear phagocytes and polymorphonuclear leukocytes examined so far have receptors on their plasma membranes for C3b.
In some cells, the binding of C3b-coated particles to C3b receptors requires the presence of divalent cations in the surrounding medium.
Once binding occurs, activated macrophages ingest the C3b-coated particles.
In certain microorganisms, such as Haemophilus influenzae, C3b also exhibits enzymatic activity for aromatic dipeptides present in neutrophils.
This cleavage of aromatic dipeptides on the neutrophil plasma membrane is considered an additional mechanism by which C3b mediates phagocytosis of particles to which it is bound.
Opsonins and Types
An opsonin is defined as any molecule that enhances phagocytosis by either marking an antigen for an immune response or tagging dead cells for recycling.
Opsonin molecules usually attach on one end to receptors present on the antigen and, on the other end, to receptors located on phagocytes.
This dual binding facilitates mechanisms that ultimately result in the destruction or removal of the specific antigen.
Through this process, opsonin molecules ensure that the attachment of antigens to immune cells is significantly strengthened.
Opsonins play crucial roles in the immune system, such as:
Marking dead and dying cells for clearance by macrophages and neutrophils.
Aiding in the activation of complement proteins.
Assisting in the destruction of cells by natural killer (NK) cells.
The mechanisms utilized by opsonins to accelerate the kinetics of phagocytosis involve promoting stronger interactions between opsonins and cell surface receptors on immune cells.
Opsonins also help to override the natural negative charges present on cell membranes, which would otherwise prevent two cells from coming into close contact.
Types of Opsonins
Antibodies
Antibodies are adaptive immunity molecules released by B cells as part of the immune response.
In the case of IgG antibodies, the Fc domain binds to receptors on phagocytes, while the Fab domain binds to antigens.
IgM antibodies lack Fc receptors and therefore are ineffective in directly enhancing phagocytosis.
However, IgM antibodies are highly effective in activating the complement system and are thus considered opsonins.
The binding of antibodies to both antigen and immune cells can result in the release of lysis products from effector cells.
Complement proteins
Several complement proteins, including C3b, C4b, and C1q, function as opsonins.
C3b is the most effective opsonin, as it initiates phagocytosis and is recognized by phagocyte receptors.
Complement receptor 1 (CR1), which is expressed on all phagocytes, recognizes multiple complement proteins such as C3b and C4b, making complement opsonization highly efficient.
C1q, a component of the C1 complex, interacts with the Fc region of antibodies and serves as an opsonin.
Circulating proteins
Circulating proteins such as pentraxins, collectins, and ficolins also act as opsonins.
These proteins are pattern recognition receptors (PRRs) that can coat microbes, thereby enhancing neutrophil activity through multiple mechanisms.
A key property of these proteins is their ability to bind in a Ca²⁺-dependent fashion as pattern recognition molecules.
They recognize microbial structures such as phosphorylcholine in membranes, which subsequently activates the complement system.
Collectins like Mannose Binding Lectin (MBL) form the basis of the lectin pathway of complement activation.
Ficolins typically recognize N-acetylglucosamine residues in complex carbohydrates, along with other ligands present on different antigens.
Examples of Opsonins
IgM antibodies – Although they lack Fc receptors and do not directly promote phagocytosis, IgM antibodies are highly effective at activating the complement system, which in turn leads to opsonization.
IgG antibodies – The most potent antibody opsonins; their Fc domain binds to Fc receptors on phagocytes while the Fab domain binds to antigens, promoting strong phagocytic activity.
C3b proteins – The most important and effective complement opsonin, generated from cleavage of C3, and directly recognized by complement receptors (CR1) on phagocytes.
C4b proteins – Another complement opsonin that tags pathogens for recognition by complement receptors, aiding in clearance.
C1q proteins – Part of the C1 complex; binds to the Fc portion of antibodies already attached to antigens, functioning as an opsonin.
Pentraxins – A family of circulating proteins (e.g., C-reactive protein, serum amyloid P) that act as soluble pattern recognition molecules and facilitate phagocytosis.
Collectins – Collagen-containing C-type lectins (e.g., surfactant proteins SP-A and SP-D) that bind microbial carbohydrates and act as opsonins.
Ficolins – Soluble lectins that recognize N-acetylglucosamine residues and other microbial patterns, enhancing phagocytosis.
Mannose-binding lectin (MBL) – A type of collectin that recognizes mannose and related sugars on microbial surfaces, initiating the lectin complement pathway and acting as a strong opsonin.
References
Delves, P. J., Martin, S. J., Burton, D. R., & Roitt, I. M. (2017). Roitt’s Essential Immunology (13th ed.). John Wiley & Sons, Ltd.
Owen, J. A., Punt, J., & Stranford, S. A. (2013). Kuby Immunology (7th ed.). W. H. Freeman and Company.
Thau, L., & Mahajan, K. (2020). Physiology, Opsonization. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available at: https://www.ncbi.nlm.nih.gov/books/NBK534215/
Griffin, F. M. (1977). Opsonization. In N. K. Day & R. A. Good (Eds.), Biological Amplification Systems in Immunology (Comprehensive Immunology, Vol. 2). Springer, Boston, MA.
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