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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Helminths have also evolved novel means to avoid complement-mediated damage. Trichinella spiralis, for instance, causes the disease trichinosis. Certain developmental stages of this nematode, notably the adult, which lives in the small intestine, and the encysted larvae, surviving in mammalian striated muscle cells, express calreticulin on their surfaces and secrete it into the surrounding environment. This protein can bind to and inhibit the activity of C1q, the first component in the mammalian classical complement pathway. By inactivating C1q, T. spiralis thus suppresses various complement effector functions, including chemotaxis, cell lysis and inflammation.
The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Different biological functions are associated with each of the domains of the H chain constant region. For example, the CH1 domain aids in orienting the variable regions for combining with antigen, and the CH2 domain contains the binding site for the first component of the complement cascade. The interaction between the CH2 domain and the first component of complement activates the Classical Complement Pathway. Finally, the CH3 domain binds to Fc receptors located on phagocytic cells such as macrophages. Although structurally very similar, each domain has a different role in the humoral immune response.
The maternal immune system during pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
DAF inhibits formation and accelerates decay of C3/C5 convertase, which inhibits the alternative pathway. MCP is an intrinsic-acting protein that binds efficiently to C3b attached to other molecules on the cell surface (13). MCP then cleaves the C3b or C4b components of complement to their inactive derivatives, which inhibits the classical complement pathway. Finally, CD59 inhibits the final common component of both complement pathways—the MAC. CD59 is expressed in greater amounts than either DAF or MCP, although the absence of CD59 is compatible with successful pregnancy, indicating that MCP and DAF are able to compensate for a lack of CD59.
Retinal findings in glomerulonephritis
Published in Clinical and Experimental Optometry, 2022
Heather G Mack, Deborah J Colville, Phillip Harraka, Judith Anne Savige, Alessandro Invernizzi, Samantha Fraser-Bell
Membranoproliferative glomerulonephritis was previously classified into three patterns based on immunopathology and ultrastructural location of electron dense deposits in the glomerular basement membrane. Membranoproliferative glomerulonephropathy is now classified as C3 complement-mediated disease recognising the key role of Complement 3 in its pathogenesis. When the alternative complement pathway is activated two subtypes are recognised 1) with renal dense deposits, the previous type II membranoproliferative glomerulonephritis, and 2) without dense deposits, known as C3 glomerulonephritis. C3 complement mediated glomerulonephritis may also involve the classical complement pathway (membranoproliferative glomerulonephritis type I) and both alternative and classical pathways (membranoproliferative glomerulonephritis type III).27 C3 glomerulonephropathy is associated with mutations in Complement 3, Complement factor H, complement factor B, and complement factor H-related 1, 2 and 5, as well as a circulating auto-antibody C3 nephritic factor in many individuals, and autoantibodies to factor H, C3 and factor B in some individuals.
Multi-functional antibody profiling for malaria vaccine development and evaluation
Published in Expert Review of Vaccines, 2021
D. Herbert Opi, Liriye Kurtovic, Jo-Anne Chan, Jessica L. Horton, Gaoqian Feng, James G. Beeson
Complement is an essential arm of the immune system comprising of more than 30 serum proteins, which act in a sequential cascade to mediate various immunological responses [118]. Complement can be activated by antibodies through interactions with complement protein C1q, which initiates the classical complement pathway. C1q-fixation (together with components C1r and C1s) leads to the deposition of complement protein C3 on target cells. Deposited C3 acts as an opsonin that interacts with complement receptors including CR1, CR2, C3, CR4, and CRIg that are expressed on immune cells including macrophages and neutrophils, to facilitate pathogen uptake and degradation via complement-mediated phagocytosis [118]. The terminal step in complement activation is the formation of the membrane attack complex (MAC) that inserts into the target cell membrane and causes cell lysis.
Targeting the complement system in neuromyelitis optica spectrum disorder
Published in Expert Opinion on Biological Therapy, 2021
Nithi Asavapanumas, Lukmanee Tradtrantip, Alan S. Verkman
The pathogenesis of AQP4-IgG seropositive NMOSD is now fairly well-understood, as reviewed elsewhere [1,6,17]. Briefly, pathogenic AQP4-IgG autoantibodies are thought to be generated primarily in the periphery and, by so far incompletely understood mechanisms, access astrocytes in the CNS by passage across the blood-brain barrier. AQP4-IgG binds to extracellular epitopes on AQP4 at the astrocyte plasma membrane, which initiates astrocyte injury by CDC and ADCC mechanisms. In CDC, C1q binding to the Fc region of AQP4-IgG activates the classical complement pathway, producing pro-inflammatory anaphylatoxins and causing cellular injury by formation of the pore-like membrane attack complex (MAC), as discussed further in section 2.3. In ADCC, binding of leukocytes (neutrophils, macrophages, natural killer (NK) cells) to the Fc region of AQP4-IgG through Fcγ receptors causes their activation and degranulation. The inflammatory response created by astrocyte injury, cytokine release, leukocyte infiltration, and microglial activation further disrupts the blood-brain barrier and ultimately injures oligodendrocytes and neurons. As discussed in sections 2.3 and 2.4, complement activation following AQP4-IgG binding to AQP4 on astrocytes may also cause cytotoxicity to nearby cells, including oligodendrocytes and neurons, by a bystander mechanism, and several complement-independent mechanisms, in addition to ADCC, may contribute to the pathogenesis of AQP4-IgG seropositive NMOSD.