WordNet

the 2nd letter of the Roman alphabet (同)b
the blood group whose red cells carry the B antigen (同)type_B, group B
pertaining to unconventional choices; "an alternative life style"
necessitating a choice between mutually exclusive possibilities; "alternative possibilities were neutrality or war"
a trodden path (同)footpath

PrepTutorEJDIC

(二つのうち)『どちらかを選ぶべき』,二者択一の / 代わりの / 反体制的な,現在の社会と違った価値体系を持った / 二つのものの一つを選ぶこと,二者択一 / (二者のうち)選ぶべき一方 / 代わりのもの;他にとりうる方法
道,小道(path)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/24 02:22:08」(JST)

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[Wiki en表示]

The classical and alternative complement pathways.

Alternative pathway. (Some labels are in Polish.)

The alternative pathway of the complement system is an innate component of the immune system's natural defense against infections.

The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the C3b protein directly binds the microbe.

Cascade

It is initiated by the spontaneous hydrolysis of C3, which is abundant in the blood plasma. "Tickover" occurs through the spontaneous cleavage of the thioester bond in C3 to form C3(H₂O).

This change in shape allows the binding of plasma protein Factor B, which allows Factor D to cleave Factor B into Ba and Bb.

Bb remains part of the C3(H₂O) to form C3(H₂O)Bb. This complex is also known as a fluid-phase C3-convertase. This convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b.

The alternative pathway C3-convertase consists of the activated B and C3b factors, forming an unstable compound that can become stable after binding properdin, a serum protein.

After the creation of C3 convertase, the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). Binding of another C3b-fragment to the C3-convertase of the alternative pathway creates a C5-convertase analoguous to the lectin or classical pathway.

The C5-convertase of the alternative pathway consists of C3bBbC3b also referred to as C3b₂Bb (instead of C4b2a3b in the other pathways).

Regulation

Since C3b is free and abundant in the plasma, it can bind to either a host cell or a pathogen surface. To prevent complement activation from proceeding on the host cell, there are several different kinds of regulatory proteins that disrupt the complement activation process:

Complement Receptor 1 (CR1 or CD35) and DAF (decay accelerating factor also known as CD55) compete with Factor B in binding with C3b on the cell surface and can even remove Bb from an already formed C3bBb complex
The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. Factor I requires a C3b-binding protein cofactor such as complement factor H, CR1, or Membrane Cofactor of Proteolysis (MCP or CD46)
Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b;^[1] accelerate the decay of the C3 convertase;^[2] and act as a cofactor for Factor I-mediated cleavage of C3b.^[3] Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage.
CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces.^[4]

References

^ Conrad DH, Carlo JR, Ruddy S (June 1978). "Interaction of beta1H globulin with cell-bound C3b: quantitative analysis of binding and influence of alternative pathway components on binding". J. Exp. Med. 147 (6): 1792–1805. doi:10.1084/jem.147.6.1792. PMC 2184316. PMID 567241.
^ Weiler JM, Daha MR, Austen KF, Fearon DT (September 1976). "Control of the amplification convertase of complement by the plasma protein beta1H". Proc. Natl. Acad. Sci. U.S.A. 73 (9): 3268–72. doi:10.1073/pnas.73.9.3268. PMC 431003. PMID 1067618.
^ Pangburn MK, Schreiber RD, Müller-Eberhard HJ (July 1977). "Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution". J. Exp. Med. 146 (1): 257–70. doi:10.1084/jem.146.1.257. PMC 2180748. PMID 301546.
^ McRae JL, Duthy TG, Griggs KM, et al. (May 2005). "Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive protein, and associates with lipoprotein". J. Immunol. 174 (10): 6250–6. PMID 15879123.

UpToDate Contents

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1. 補体経路 complement pathways
2. 補体系の概要および臨床的評価 overview and clinical assessment of the complement system
3. 補体系の制御因子および受容体 regulators and receptors of the complement system
4. 小児における補完剤および代替剤の概要 overview of complementary and alternative medicine in pediatrics
5. 癌に対する補完代替療法 complementary and alternative therapies for cancer

English Journal

Use of Dodecahedron "VLPs" as an Alternative to the Whole Adenovirus.

Fender P.SourceUnit of Virus Host Cell Interactions (UMI-3265:CNRS/UJF/EMBL), Grenoble, France.
Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2014;1089:61-70. doi: 10.1007/978-1-62703-679-5_4.
During human adenovirus type 3 (Ad3) infection, an excess of penton base and fiber proteins are produced. These form dodecahedral particles composed of 12 pentamers of penton base and 12 trimers of fiber protein. Beside this "natural" expression, the adenovirus dodecahedron can be expressed in the h
PMID 24132477

Tailor-made mutations in Arabidopsis using zinc finger nucleases.

Qi Y, Starker CG, Zhang F, Baltes NJ, Voytas DF.SourceDepartment of Genetics, Cell Biology & Development and Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA.
Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2014;1062:193-209. doi: 10.1007/978-1-62703-580-4_10.
Zinc finger nucleases (ZFNs) are proteins engineered to make site-specific double-strand breaks (DSBs) in a DNA sequence of interest. Imprecise repair of the ZFN-induced DSBs by the nonhomologous end-joining (NHEJ) pathway results in a spectrum of mutations, such as nucleotide substitutions, inserti
PMID 24057367

Japanese Journal

ヒトDNAポリメラーゼシータ(POLQ)の発見とオルタナティブエンドジョイニング(Alt-EJ)における役割

放射線生物研究 = Radiation biology research communications : 放射線生物研究会機関誌 52(1), 35-47, 2017-03
NAID 40021183629

補体関連疾患と遺伝子異常

腎臓内科・泌尿器科 = Nephrology & urology 5(1), 100-106, 2017-01
NAID 40021073409

Comparative transcriptomic analysis identifies reprogramming and differentiation genes differentially expressed in UiPSCs and ESCs

BioScience Trends 11(3), 355-359, 2017
NAID 130005853646

Related Pictures

★リンクテーブル★

リンク元	「補体」「プロパージン」「B」「第二経路」「別経路」
拡張検索	「alternative pathway complement C3-C5 convertase」「alternative pathway complement C3 convertase」「alternative pathway complement C5 convertase」
関連記事	「alternative」「pathway」「alternatives」

「補体」

　　[★]

英: complement
同: アレキシン alexin
関: 補体活性化経路、補体価

図：IMM.63

pathway	start	first step
classical pathway	antigen-antibody complex	C1q, C1r, C1s, C4, C2
lectin pathway	mannose-binding lectin or ficolin binds carbohydrate on pathogen surface	MBL/ficolin, MASP-2, C4, C2
alternative pathway	pathogen surface	C3, B, D

補体の相互作用 IMM.62

古典的経路 classical pathway

C1qがカスケードの最初となる。3つの方法で補体カスケードがはじまる。

(1)多価陰イオン表面(例えば、グラム陰性細菌のリポテイコ酸)
(2)バクテリアの多糖のホスホコリンに結合(例えば肺炎球菌のC蛋白質)
(3)抗原抗体複合体に結合して自然免疫と獲得免疫のエフェクター機構を結びつける。

レクチン経路 lectin pathway

炭化水素鎖を認識するレクチンがカスケードの最初となる。

1. lectin MBL：mannose-containing carbohydrates
2. ficolin　：N-acetylglucosamine

代替経路 alternative pathway

C3からはじまる。血漿中のC3が病原体の表面で自発的に活性化されることで補体反応がはじまる。

３つの経路は共通してC3 convertaseを生成。C3 convertaseはC3→C3a+C3b
C3a: C3a is a peptide mediator of local inflammation
C3b: C3b binds covalently to the bacterial cell membrane and opsonizes the bacteria

C5 convertaseはC3bにC3 convertaseが結合してできる
C5 converaseはC5→C5a+C5b
C5a: powerful peptide mediator of inflammation
C5b: C5b,C6,C7,C8,C9: membrane-attack complex

C3aとC5a。C4a

炎症部位に血管外に抗体、補体、食細胞を集め、組織液を増やすことで抗原提示細胞がリンパ節に移動するのを促進する(IMM.75)

C5a,C3a,C4a: smooth muscle contraction.(IMM.75)
C5a,C3a: act on the endo thelial cells lining blood vessels to induce adhesion molecules.(IMM.75)
C5a>C3a>C4a: increase in blood flow, increase vascular permeability, increase binding of phagocytes to exdothielial cells.(IMM.76)
C5a: activates mast cells to release mediators, such as histamine and TNF-α. that contribute the inflammatory response(IMM.76).
C5a: acts directly on neutrophils and monocytes and attracting neutrophils and monocytes(IMM.75)
C3a: contributes to the pypotension and edema seen in endotoxic shock
C5a: activated by endotoxin, funcions in neutrophil chemotaxis

C5a

臨床関連

増加：

関節リウマチ、ウェゲナー肉芽腫、リウマチ熱、ベーチェット病

減少：低補体血症

全身性エリテマトーデス、悪性関節リウマチ、急性糸球体腎炎、膜性増殖性糸球体腎炎、結節性多発動脈炎, polyarteritis nodosa, PN

「プロパージン」

　　[★]

英: properdin
同: プロパジン、プロペルジン; factor P
関: 補体、complement-regulatory protein

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プロパージン : 64 件
プロパジン : 約 4,060 件
プロペルジン : 約 64 件

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プロパジン properdin : 12 件
プロペルジン properdin : 28 件