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Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. (2025). 9781464189784 ISBN 9781464189784 Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. eaten) by phagocytes (cells that specialise in phagocytosis, i.e. cellular eating). Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens (such as bacteria), Cancer cell, aged cells, dead or dying cells (such as Apoptosis cells), excess synapses, or protein aggregates (such as amyloid plaques). Opsonins help clear pathogens, as well as dead, dying and diseased cells.
Opsonins were discovered and named "opsonins" in 1904 by Wright and Douglas, who found that incubating bacteria with blood plasma enabled phagocytes to phagocytose (and thereby destroy) the bacteria. They concluded that: "We have here conclusive proof that the blood fluids modify the bacteria in a manner which renders them a ready prey to the phagocytes. We may speak of this as an "opsonic" effect (opsono - I cater for; I prepare victuals for), and we may employ the term "opsonins" to designate the elements in the blood fluids which produce this effect."
Subsequent research found two main types of opsonin in blood that opsonised bacteria: complement proteins and Antibody. However, there are now known to be at least 50 proteins that act as opsonins for pathogens or other targets.
All cell membranes have negative charges (zeta potential) which makes it difficult for two cells to come close together. When opsonins bind to their targets they boost the kinetics of phagocytosis by favoring interaction between the opsonin and cell surface receptors on immune cells. This overrides the negative charges from cell membranes.
It is important that opsonins do not tag healthy, non-pathogenic cells for phagocytosis, as phagocytosis results in digestion and thus destruction of targets. Therefore, Some opsonins (including some complement proteins) have evolved to bind pathogen-associated molecular patterns, molecules only found on the surface of pathogens, enabling phagocytosis of these pathogens, and thus innate immunity. Antibodies bind to antigens on the pathogen surface, enabling adaptive immunity. Opsonins that opsonise host body cells (e.g. GAS6 that opsonises apoptotic cells) bind to "eat-me" signals (such as phosphatidylserine) exposed by dead, dying or stressed cells.
Both Immunoglobulin M and IgG undergo conformational change upon binding antigen that allows complement protein C1q to associate with the Fc region of the antibody. C1q association eventually leads to the recruitment of complement C4b and C3b, both of which are recognized by complement receptor 1, 3, and 4 (CR1, CR3, CR4), which are present on most phagocytes. In this way, the complement system participates in the adaptive immune response. C3d, a cleavage product of C3, recognizes pathogen-associated molecular patterns (PAMPs) and can opsonize molecules to the CR2 receptor on B cells. This lowers the threshold of interaction required for B cell activation via the B-cell receptor, and aids in the activation of the adaptive response.
Mannose-binding lectins, or ficolins, along with pentraxins and are able to recognize certain types of that are expressed on the cell membranes of bacteria, Fungus, , and Parasitism, and can act as opsonin by activating the complement system and phagocytic cells.
Members of the Pentraxins family can bind to apoptotic cell membrane components like phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Immunoglobulin M antibodies also bind to PC. Collectin molecules such as mannose-binding lectin (MBL), surfactant protein A (SP-A), and SP-D interact with unknown ligands on apoptotic cell membranes. When bound to the appropriate ligand these molecules interact with phagocyte receptors, enhancing phagocytosis of the marked cell.
C1q is capable of binding directly to apoptotic cells. It can also indirectly bind to apoptotic cells via intermediates like IgM autoantibodies, MBL, and pentraxins. In both cases C1q activates complement, resulting in the cells being marked for phagocytosis by C3b and C4b. C1q is an important contributor to the clearance of apoptotic cells and debris. This process usually occurs in late apoptotic cells.
Opsonization of apoptotic cells occurs by different mechanisms in a tissue-dependent pattern. For example, while C1q is necessary for proper apoptotic cell clearance in the peritoneal cavity, it is not important in the lungs where SP-D plays an important role.
SP-A opsonizes a number of bacterial and viral pathogens for clearance by lung alveolar macrophages.
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