Opsonins are proteins of the innate and adaptive immune system that facilitate phagocytosis and cell lysis by “marking” antigen.[1] Opsonization, then, is the modification of antigens by opsonins to make them more accessible to phagocytic cells and other immune cells.[1] Opsonins bind to antigen and are recognized by receptors on immune cells.[1]
Opsonins of the innate immune system largely comprise complement proteins, though interaction between complement proteins and antibodies constitutes an adaptive immune response.[2] Antibodies independently serve as opsonic molecules in the adaptive response.[3]
Opsonin proteins bind to surface molecules or membranes of pathogens, and receptors on phagocytic cells bind to opsonins to initiate phagocytosis.[2][3][4] Opsonization helps clear pathogens, dying cells, and marks diseased cells.[1]
Varieties edit
Adaptive Opsonization edit
Antibodies are synthesized by B cells and are secreted in response to recognition of specific antigenic epitopes, and bind only to specific epitopes (regions) on an antigen.[3] They comprise the adaptive opsonization pathway, and are composed of two fragments: the antigen binding region (Fab region) and the fragment crystallizable region (Fc region).[3] The Fab region is able to bind to a specific epitope on an antigen, such as a specific region of a bacterial surface protein.[3] The Fc region of IgG is recognized by the Fc Receptor (FcR) on natural killer cells and other effector cells; the binding of IgG to antigen causes a conformational change that allows FcR to bind the Fc region and initiate attack on the pathogen through the release of lytic products.[3] Antibody may also tag tumor cells or virally infected cells, with NK cells responding via the FcR; this process is known as antibody-dependent cellular cytotoxicity (ADCC).[3]
Both IgM and IgG undergo conformational change upon binding antigen that allows complement protein C1q to associate with the Fc region of the antibody.[4] 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.[4] 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.[4] 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.[4]
Innate Opsonization edit
The complement system, independently of the adaptive immune response, is able to opsonize pathogen before adaptive immunity may even be required.[2][4] Complement proteins involved in innate opsonization include C4b, C3b and iC3b.[5] In the alternative pathway of complement activation, circulating C3b is deposited directly onto antigens with particular PAMPs, such as lipopolysaccharides on gram-negative bacteria.[5] C3b is recognized by CR1 on phagocytes. iC3b attaches to apoptotic cells and bodies and facilitates clearance of dead cells and remnants without initiating inflammatory pathways, through interaction with CR3 and CR4 on phagocytes.[2]
Mannose-binding lectins, or ficolins, are able to recognize certain types of carbohydrates that are expressed on the cell membranes of bacteria, fungi, viruses, and parasites, and can act as opsonin by activating the complement system and phagocytic cells.[4]
References edit
- ^ a b c d Punt, Jenni (2019). Kuby immunology. Sharon A. Stranford, Patricia P. Jones, Judith A. Owen (Eighth edition ed.). New York. ISBN 978-1-4641-8978-4. OCLC 1002672752.
{{cite book}}:|edition=has extra text (help)CS1 maint: location missing publisher (link) - ^ a b c d Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T. (2015). "Complement System Part II: Role in Immunity". Frontiers in Immunology. 6: 257. doi:10.3389/fimmu.2015.00257. ISSN 1664-3224. PMC 4443744. PMID 26074922.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c d e f g Chiu, Mark L.; Goulet, Dennis R.; Teplyakov, Alexey; Gilliland, Gary L. (2019-12-03). "Antibody Structure and Function: The Basis for Engineering Therapeutics". Antibodies. 8 (4). doi:10.3390/antib8040055. ISSN 2073-4468. PMC 6963682. PMID 31816964.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c d e f g Varela, Juan Carlos; Tomlinson, Stephen (2015-6). "COMPLEMENT: AN OVERVIEW FOR THE CLINICIAN". Hematology/oncology clinics of North America. 29 (3): 409–427. doi:10.1016/j.hoc.2015.02.001. ISSN 0889-8588. PMC 4456616. PMID 26043382.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Ricklin, Daniel; Hajishengallis, George; Yang, Kun; Lambris, John D (2010-08-19). "Complement: a key system for immune surveillance and homeostasis". Nature Immunology. 11 (9): 785–797. doi:10.1038/ni.1923. ISSN 1529-2908.