Antibody-dependent cell-mediated cytotoxicityantibody-dependent cell-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity hd picture
The antibody-dependent cell-mediated cytotoxicity ADCC, also referred to as antibody-dependent cellular cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies1 It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection2
ADCC is independent of the immune complement system that also lyses targets but does not require any other cell ADCC requires an effector cell which classically is known to be natural killer NK cells that typically interact with IgG antibodies3 However, macrophages, neutrophils and eosinophils can also mediate ADCC, such as eosinophils killing certain parasitic worms known as helminths via IgE antibodies4
ADCC is part of the adaptive immune response due to its dependence on a prior antibody response The coating of target cells with antibodies is sometimes referred to as opsonization
- 1 By NK cells
- 2 By eosinophils
- 3 In vitro Assays
- 4 Monoclonal antibody action against cancer
- 5 References
- 6 Further reading
- 7 External links
By NK cellsedit
The typical ADCC involves activation of NK cells by antibodies A NK cell expresses Fc receptors, mostly CD16 These receptors recognize, and bind to, the Fc portion of an antibody, such as IgG, which has bound to the surface of a pathogen-infected target cell The most common Fc receptor on the surface of an NK cell is called CD16 or FcγRIII Once the Fc receptor binds to the Fc region of IgG, the Natural Killer cell releases cytotoxic factors that cause the death of the target cell
During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell Antibodies can then bind to these viral proteins Next, the NK cells which have Fc Receptors will bind to that antibody, inducing the NK cell to release proteins such as perforin and proteases known as granzymes, which causes the lysis of the infected cell to hinder the spread of the virus
Furthermore, NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface, indicating a non-self cell This is because, generally, all nucleated cells which excludes RBCs of the body contain MHC I
Large parasites like helminths are too big to be engulfed and killed by phagocytosis They also have an external structure or integument that is resistant to attack by substances released by neutrophils and macrophages After IgE coat these parasites, the Fc receptor FceRI of an eosinophil will then recognize IgE Subsequently, interaction between FceRI and the Fc portion of helminth-bound IgE signals the eosinophil to degranulate
In vitro Assaysedit
Several laboratory methods exist for determining the efficacy of antibodies or effector cells in eliciting ADCC Usually, a target cell line expressing a certain surface-exposed antigen is incubated with antibody specific for that antigen After washing, effector cells expressing Fc receptor CD16 are co-incubated with the antibody-labelled target cells Effector cells are typically PBMCs peripheral blood mononuclear cell, of which a small percentage are NK cells Natural Killer cell; less often they are purfied NK cells themselves Over the course of a few hours a complex forms between the antibody, target cell, and effector cell which leads to lysis of the cell membrane of the target If the target cell was pre-loaded with a label of some sort, that label is released in proportion to the amount of cell lysis Cytotoxicity can be quantified by measuring the amount of label in solution compared to the amount of label that remains within healthy, intact cells
The classical method of detecting this is the Chromium-51 51Cr release assay; the Sulfur-35 35S release assay is a little used radioisotope-based alternative Target cell lysis is determined by measuring the amount of radiolabel released into the cell culture medium by means of a gamma counter or scintillation counter A variety of non-radioactive methods are now in widespread use Fluorescence-based methods include such things as direct labeling with a fluorescent dye like calcein or labeling with europium that becomes fluorescent when released Eu3+ binds to a chelator Fluorescence can be measured by means of multi-well fluorometers or by flow cytometry methods There are also enzymatic-based assays in which the contents of the lysed cells includes cellular enzymes like GAPDH that remain active; supplying a substrate for that enzyme can catalyze a reaction whose product can be detected by luminescence or by absorbance
Monoclonal antibody action against canceredit
The effects against solid tumors of trastuzumab and rituximab monoclonal antibodies have been shown in experiments with mice to involve ADCC as an important mechanism of therapeutic action5 In the clinic, the FcgRIII 158V/F polymorphism interfere with the ability to generate ADCC responses in vitro during trastuzumab treatment
Multiple myeloma circulating in blood can be treated with daratumumab Darzalex monoclonal antibody6 Studies with in vitro materials and patient materials indicate that ADCC is an important mechanism, along with CDC Complement-dependent cytotoxicity7
See also Afucosylated monoclonal antibodies
- ^ Hashimoto, G; Wright, P F; Karzon, D T 1983-11-01 "Antibody-dependent cell-mediated cytotoxicity against influenza virus-infected cells" The Journal of Infectious Diseases 148 5: 785–794 ISSN 0022-1899 PMID 6605395 doi:101093/infdis/1485785
- ^ Pollara, Justin; Hart, Lydia; Brewer, Faraha; Pickeral, Joy; Packard, Beverly Z; Hoxie, James A; Komoriya, Akira; Ochsenbauer, Christina; Kappes, John C 2011-08-01 "High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses" Cytometry Part A 79 8: 603–612 ISSN 1552-4930 PMC 3692008 PMID 21735545 doi:101002/cytoa21084
- ^ Wang, W; Erbe, AK; Hank, JA; Morris, ZS; Sondel, PM 2015 "NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy" Front Immunol 6: 368 PMC 4515552 PMID 2628406 doi:103389/fimmu201500368 Retrieved 28 April 2017
- ^ Capron, M; Kazatchkine, MD; Fischer, E; Joseph, M; Butterworth, AE; et al 1987 "Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated cytotoxicity against schistosomes" J Immunol 139 6: 2059–65 CS1 maint: Explicit use of et al link
- ^ Clynes, RA; Towers, TL; Presta, LG; Ravetch, JV 2000 "Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets" Nat Med 6 4: 443–6 PMID 10742152 doi:101038/74704
- ^ Sanchez, L; Wang, Y; Siegel, DS 2016 "Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma" J Hematol Oncol 9 1: 51 PMC 4929758 PMID 27363983 doi:101186/s13045-016-0283-0 Retrieved 28 April 2017
- ^ de Weers, M; Tai, YT; Bakker, JM; Vink, T; Jacobs, DC; et al 2011 "Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors" J Immunol 186 3: 1840–8 PMID 21187443 doi:104049/jimmunol1003032 Retrieved 28 April 2017 CS1 maint: Explicit use of et al link
- Janeway CA, Jr; et al 2001 Immunobiology 5th ed Garland Publishing ISBN 0-8153-3642-X electronic full text via NCBI Bookshelf
- Pier GB, Lyczak JB, Wetzler LM 2004 Immunology, Infection, and Immunity ASM Press ISBN 1-55581-246-5
- University of Leicester, Virus Immunopathology Notes
- Antibody-Dependent Cell Cytotoxicity at the US National Library of Medicine Medical Subject Headings MeSH
antibody-dependent cell-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity (adcc, antibody-dependent cell-mediated cytotoxicity (adcc), antibody-dependent cell-mediated cytotoxicity hd picture
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