Classical complement pathway: Difference between revisions

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Immunotherapies have been developed to detect and destroy cells infected by the HIV virus via classical complement activation.<ref>{{Cite journal|title = Synthetic immunotherapy induces HIV virus specific Th1 cytotoxic response and death of an HIV-1 infected human cell line through classic complement activation|journal = Virology Journal|date = 2013-04-04|volume = 10|issue = 1|doi = 10.1186/1743-422x-10-107|pmid = 23557359|pmc = 3626621|language = En|first = Olga|last = Pleguezuelos|first2 = Gregory A|last2 = Stoloff|first3 = Wilson|last3 = Caparrós-Wanderley|pages=107}}</ref> This process involves creating synthetic peptides that target conserved regions in HIV specific proteins and induce an antibody specific immune response through IgG antibodies. This is important for targeting the virus in its intracellular phase because the antibodies specific to the synthetic peptides can trigger the classical complement pathway and induce the death of HIV infected cells.

Classical complement activation has also been shown to combat Methicillin-resistant Staphylococcus aureus.<ref>{{Cite journal|title = Complement activation contributes to the anti-methicillin-resistant Staphylococcus aureus effect of natural anti-keratin antibody|journal = Biochemical and Biophysical Research Communications|date = 2015-05-22|pages = 142–147|volume = 461|issue = 1|doi = 10.1016/j.bbrc.2015.03.182|first = Jingang|last = An|first2 = Zhengxiao|last2 = Li|first3 = Yingying|last3 = Dong|first4 = Jiawen|last4 = Wu|first5 = Jianwen|last5 = Ren|pmid=25862372}}</ref> Certain variants of the IgM antibody were found to bind the Methicillin-resistant ''[[Staphylococcus aureus]]'' these IgM were found to be critical in complement activation through the classical pathway and subsequent destruction of the bacteria. Therapies that utilize classical complement activation have been shown to be effective in targeting and killing cancer cells and destroying tumors.<ref>{{Cite journal|title = Tachyplesin Activates the Classic Complement Pathway to Kill Tumor Cells|url = http://cancerres.aacrjournals.org/content/65/11/4614|journal = Cancer Research|date = 2005-06-01|issn = 0008-5472|pmid = 15930279|pages = 4614–4622|volume = 65|issue = 11|doi = 10.1158/0008-5472.CAN-04-2253|language = en|first = Jinguo|last = Chen|first2 = Xue-Ming|last2 = Xu|first3 = Charles B.|last3 = Underhill|first4 = Shanmin|last4 = Yang|first5 = Luping|last5 = Wang|first6 = Yixin|last6 = Chen|first7 = Shuigen|last7 = Hong|first8 = Karen|last8 = Creswell|first9 = Lurong|last9 = Zhang|doi-access = free}}</ref> [[Tachyplesin]], a small peptide, has been shown to exhibit these effects. When injected into target tissue encourages recruitment of C1q and activates downstream events, eventually leading to the formation of the C5b-9 complex which damages tumor cells, killing them.

Lack of regulation of the classical complement pathway through the deficiency in [[C1-inhibitor]] results in episodic [[angioedema]].<ref name="Overview of Complement" /> C1-inhibitor defiency can be hereditary or acquired, resulting in hereditary or acquired angioedema.<ref name="angiodema"/> C1-inhibitor plays the role of inactivating C1r and C1s to prevent further downstream classical complement activity.<ref>{{Cite journal|last=Levy|first=Michael|last2=Mealy|first2=Maureen A.|date=2014-06-01|title=Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica|journal=Neurology: Neuroimmunology & Neuroinflammation|language=en|volume=1|issue=1|pages=e5|doi=10.1212/nxi.0000000000000005|issn=2332-7812|pmid=25340061|pmc=4202676}}</ref><ref name="angiodema">{{Cite journal|last=Cugno|first=Massimo|last2=Zanichelli|first2=Andrea|last3=Foieni|first3=Fabrizio|last4=Caccia|first4=Sonia|last5=Cicardi|first5=Marco|title=C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress|journal=Trends in Molecular Medicine|volume=15|issue=2|pages=69–78|doi=10.1016/j.molmed.2008.12.001|pmid=19162547|year=2009}}</ref> C1-inhibitor controls the processes involved in maintaining vascular permeability. As a result, C1-inhibitor levels of less than 50% of the standard lead to increased vascular permeability, characteristic of angioedema.<ref name="angiodema" /> Cinryze, a human plasma derived C1-esterase inhibitor, has been approved for use in 2008 for the prevention of hereditary angioedema attacks.<ref>{{Cite journal|last=Lunn|first=Michael|date=2010-08-24|title=Cinryze&trade; as the first approved C1 inhibitor in the USA for the treatment of hereditary angioedema: approval, efficacy and safety|journal=Journal of Blood Medicine|language=English|volume=1|pages=163–70|doi=10.2147/jbm.s9576|pmid=22282695|pmc=3262319}}</ref><ref>{{cite web |url=https://www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm150480.htm |title=Approval History, Letters, Reviews and Related Documents - CINRYZE |website= |accessdate=2015-01-21}}</ref>