Opsonization

Pieter S Hiemstra and Mohamed R Daha, Department of Pulmonology, Leiden University Hospital, Leiden, The Netherlands

Copyright © 1998 Elsevier Ltd. All Rights Reserved.

Phagocytes (granulocytes, monocytes and macrophages) can kill a wide variety of prokaryotic and eukaryotic cells, including microorganisms and tumor cells. Killing can occur intracellularly after endocytosis (e.g. after phagocytosis of bacteria) or extracellularly by secretion of factors from the phagocytes that are harmful to the foreign cell. In both cases, recognition of the particle by the phagocyte is essential. It has been known for more than 90 years that recognition and ingestion of microorganisms by phagocytes is facilitated by the binding of serum factors (opsonins) to these microorganisms.

In 1903, Wright and Douglas discovered that the uptake of staphylococci by human granulocytes is enhanced by serum. They concluded that 'the body fluids modify the bacteria in a manner which renders them a ready prey to the phagocytes'. This opsonic effect of serum (L. opsono, 'I cater for'; 'I prepare victuals for') was reduced, but not completely lost, when the serum was heated. Nowadays it is known that the major heat-stable opsonin is immunoglobulin G (IgG), whereas the major heat-labile component in the opsonization process is composed of components of the complement system.

Receptors for IgG and complement are the best characterized receptors involved in recognition and phagocytosis, but receptors for IgE and IgA may also serve as opsonin receptors. Antibodies and complement components usually act synergistically in the opsonization of particles (Figure 1). In addition to these opsonins, other factors may stimulate the ingestion of particles, including acute phase proteins, col-lectins, defensins, extracellular matrix components and tuftsin. Microorganisms that are not opsonized can also be recognized by phagocytes because of, for example, the presence of carbohydrate residues

Phagocyte

Phagocyte

IgG + complement

Complement

IgG + complement

Complement

Figure 1 Opsonization by IgG alone, IgG and complement, and complement alone, and interaction of these opsonins with specific membrane receptors present on phagocytes.

(mannose, L-fucose, galactose, glucose and N-acetyl-neuraminic acid) on the microorganisms that bind to sugar-specific receptors on macrophages. Also, receptors belonging to the CD11/CD18 integrin famib may mediate the binding of unopsonized microorganisms to phagocytes, indicating that these receptors are involved in the phagocytosis of both opsonized and nonopsonized microorganisms.

Immunoglobulins Immunoglobulin G

The capacity of antibodies of the IgG class to promote phagocytosis is well established. IgG increases the uptake of particles by an interaction with receptors for IgG (Fey receptors) that are present on phagocytes. In humans, immunoglobulins of the IgGl and IgG3 subclasses are the most effective heat-stable opsonins, and are the subclasses that are bound with the highest affinity to Fey receptors. Binding to antigenic determinants on the particles is mediated by the Fab fragment of the IgG molecule, whereas the Fc part of IgG interacts with Fey receptors on the phagocyte cell membrane. Human phagocytes can express three classes of Fey receptors (FcyRI, FcyRII and FcyRIII) that have different and partly overlapping functions. The low-affinity FcyRII is probably the receptor that is most important in mediating phagocytosis of IgG-coated particles. For the interaction between IgG and its receptor, it is essential that IgG is located on the outer surface of the particle (e.g. the bacterial capsule), where its Fc part is accessible to the Fey receptor.

In addition to forming a bridge between the particle and the phagocyte, IgG enhances the uptake of bacteria by increasing their hydrophobicity. This mechanism is probably less important than the aforementioned specific interaction between the IgG-opsonized particle and the phagocytic Fey receptor.

Immunoglobulin M

Human phagocytes do not bear a receptor for Ig.VI on their surface. Therefore IgM itself cannot act as an opsonin. However, since IgM is a very effective activator of the classical pathway of the complement system, IgM-coated particles can be opsonized with complement components, and thus be recognized by phagocytes.

Immunoglobulin A

Two types of receptors that may mediate binding and ingestion of IgA-coated particles are present on the cell surface of phagocytes: receptors for the constant part of IgA (FcRa) and the asialoglycoprotein receptor (ASR). IgA was originally though to lack opsonic activity, or even to act as a dysopsonin (a molecule that inhibits phagocytosis). Recent reports demonstrate the capacity of IgA to promote phagocytosis of microorganisms and erythrocytes. Since IgA activates the alternative pathway of complement, opsonization of particles by IgA may be enhanced by the binding of complement components to the particle.

Immunoglobulin D

No opsonic activity for IgD has been reported. Immunoglobulin E

High-affinity receptors for IgE (FceRI) are present on mast cells and basophils, and low-affinity receptors (FceRII) on macrophages, eosinophils and platelets. The expression of FceRII on monocytes can be induced by interleukin 4 (IL-4). The main function of the phagocytic FceRII receptor resides in the defense against parasites. Since most parasites are too large to be ingested, IgE usually does not act as an opsonin.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment