Immunology of lung transplantation
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
The complement system consists of three major pathways referred to as classical, lectin, and alternative. Constituents of the system include a complex array of proteins that are divided into circulating complement produced by the liver and localized complement components produced by cells migrating to or present in tissues.35 Complement activation results in phagocytic removal or cellular lysis by membrane attack complex formation, as well as in the generation of inflammatory mediators.36 The most critical components involved in this process are C3 and C5 and their cleavage products. The action of activated complement proteins is subsequently regulated by complement regulatory proteins, including CD55 (also known as decay-accelerating factor [DAF]) and CD46.37,38
Ganglioside GD2 Specific Antibodies in the Diagnosis and Therapy of Human Neuroblastoma
John T. Kemshead in Pediatric Tumors: Immunological and Molecular Markers, 2020
Both the IgM and the IgG3 MAb to GD2 activate human complement efficiently in tumor cytotoxicity.20,25 Using the Hoechst stain method20 to monitor the rare tumor cells, as many 10% tumor cells in the bone marrow can be eliminated without damaging normal marrow stem cells. Normal human cells are resistant to complement lysis because of the presence of decay-accelerating factor (DAF) on their cell surface.16 However, neuroblastomas and many melanomas have low to absent expression of this protein and, therefore, are very sensitive to human complement. This sensitivity of human neuroblastoma cells to complement has important therapeutic implications. With the activation of human complement, anaphylatoxic and chemotactic properties of activated complement fragments can play an important role in the formation of local inflammatory response as well as the influx of important effector cells to tumor sites. Complement receptors for C3b and C3bi are present on granulocytes and natural killer cells. Since C3b and C3bi are deposited on tumor cells after MAb activation of human complement, they may enhance such cell mediated tumor cytotoxicity.
Host Defense I: Non-specific Immunity
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Several membrane components act to protect cells from complement lysis. Decay accelerating factor (DAF) is anchored in the cell membranes of erythrocytes, leukocytes, platelets, and endothelial cells. This protein interacts with complement complexes deposited on the cell’s surface and, as its name suggests, hastens their dissociation. Membrane cofactor protein (MCP) is found on leukocytes and platelets. It binds to C3b and iC3b and appears to enhance the activity of factor I. Homologous restriction factor (HRF) has a distribution similar to that of DAF. This protein binds to C8 and C9 and inhibits formation of an effective lytic unit. CD59 (also known as membrane attack complex inhibition factor, or membrane inhibitor of reactive lysis) has activity similar to HRF.
The Complement System in Retinal Detachment with Choroidal Detachment
Published in Current Eye Research, 2022
Shasha Luo, Yanghao Chen, Lufei Yang, Xuechun Gong, Zhifeng Wu
Complement regulatory protein DAF is a glycosylated membrane protein.15 To the best of our knowledge, this may be the first quantitative measurement of sDAF in the vitreous fluid of eyes with either RRDCD or RRD. An elegant study has shown that sDAF in urine has C4bp (or factor H) activity, indicating that it can inhibit the liquid phase activation of the complement cascade, which is equivalent to the role of serum C4–binding protein.16 Complement factor I (C3bINH) is an esterase that is a C3b inhibitory factor that can cleave and inactivate C3b to become the ineffective iC3B. It can also cleave C4b into C4d and C4c, thereby inhibiting the activation of the complement system.17 In the RRDCD group, the levels of sDAF and CFI in the vitreous humor were significantly increased, further indicating that eyes with RRDCD may still have normal complement regulation mechanisms, but that some persistent inflammatory mechanisms cause the continuous activation of the complement pathway and the level of complement inhibitory factors increase accordingly. Interestingly, the CFD and C2 were higher in the RRD group than in the control group, and the downstream components were not activated. This phenomenon may occur due to the increased levels of CFI.
Pregnancy immune tolerance at the maternal-fetal interface
Published in International Reviews of Immunology, 2020
Xiaopeng Li, Jiayi Zhou, Min Fang, Bolan Yu
The complements system plays a significant role in inflammatory process against infectious and toxic agents. During pregnancy, if unrestricted, complement activation will induce inflammation to damage the fetal tissues. Therefore, it is crucial to control the complement system activity for fetus protection. In mice, the complement regulator Crry protein is highly expressed in trophoblasts and decidual cells which inhibits complement activation, protecting the fetus from complement-mediated damage.148 In human, three membrane proteins, the decay accelerating factors (DAF, CD55), membrane cofactor proteins (MCP, CD46), and CD59 expressed by trophoblasts and decidual cells can suppress complement activation by blocking C3, C4 activation.149,150 Previous studies showed that the pregnancy loss was related to lower DAF expression on the placenta and increased complement consumption at the maternal-fetal interface.149 Moreover, MCP polymorphism is associated with recurrent spontaneous abortion.151 These data suggest that controlling the complement system in an appropriate state is important to maintain healthy pregnancy, and the complement cascade might be a potential target for therapies to prevent poor pregnancy outcomes.
Regulation of antibody-mediated complement-dependent cytotoxicity by modulating the intrinsic affinity and binding valency of IgG for target antigen
Published in mAbs, 2020
Bo Wang, Chunning Yang, Xiaofang Jin, Qun Du, Herren Wu, William Dall’Acqua, Yariv Mazor
To further comprehend the role of format valency in the capacity of mAbs to regulate CDC, we examined the effect of silencing membrane-bound complement regulatory proteins (mCRPs) in tumor cells on the ability of monovalent and bivalent antibody formats to elicit CDC. Complement regulatory proteins, including membrane cofactor protein (CD46), decay accelerating factor (CD55), and protectin (CD59), are a group of cell surface proteins that can significantly inhibit CDC.10,52 These membrane regulators are indispensable for keeping CDC function under check and for preventing complement-mediated attack of normal cells.10,52 Previous studies have shown that many tumor cells overexpress mCRPs to attenuate CDC.42,52–54 Neutralization of mCRPs by either blocking antibodies or down-regulation with siRNAs was recently reported to enhance the CDC activity of anti-tumor antibodies.34,35
Related Knowledge Centers
- Alternative Complement Pathway
- Classical Complement Pathway
- Lectin Pathway
- Protein
- Glycoprotein
- Gene
- Complement System
- Cell
- C3-Convertase
- Complement Membrane Attack Complex