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C1q
HISTORIA
LISTER (1881), Von Fodor (1887), Nuttall
(1888) y Buchner (1889) sealaron la accin
destructora de la sangre normal sobre ciertas
bacterias patgenas. Nuttall demostr el
poder ltico de la sangre de varias especies
animales sobre los bacilos del carbunco, pero
observ que esta accin se perda si la sangre
se conservaba unos das o se calentaba a 60C.
BORDET comprob que la adicin de suero
fresco inmune produca la lisis de Vibrio
cholerae, pero cuando el suero envejeca o se
calentaba a 55C durante media hora perda
su capacidad ltica. La adicin de suero normal
al suero calentado, sin embargo, restableca el
poder ltico. En consecuencia Bordet lleg a la
conclusin de que la accin del suero inmune
se deba a dos sustancias:
1) Una sustancia termoestable, presente en
el suero inmune (suero con anticuerpos
contra Vibrio cholerae) pero no en el
normal, que preparaba a la bacteria, para
la accin de la segunda sustancia.
2) Un producto termolbil, la ALEXINA (voz
griega que significa, evitar, desviar el
golpe, proteger), que era capaz de
complementar la reaccin antgenoanticuerpo produciendo finalmente la lisis
de las bacterias. Dicha sustancia actuaba
complementando dicha reaccin. De ah
C1qrs
1. Va Clsica
2. Va Alterna o de Properdn
3. Va de las Lectinas.
1. VIA CLSICA
En la va clsica intervienen en la reaccin de
cascada
las
siguientes
protenas
o
denominadas fracciones de complemento C1q,
C1r, C1s, C4, C2, C3, C5, C6, C7, C8 y C9. Para
un mejor entendimiento comentaremos de
tres agrupaciones que forman estas protenas
a fin de cumplir su funcin:
Unidad de reconocimiento formada por el C1q,
C1r y el C1s.
Unidad de activacin formada por el C4, C2 y
el C3.
Unidad de ataque formada por el C5 al C9.
Fase de reconocimiento previamente debi
ocurrir la reaccin antgeno-anticuerpo y en
estas circunstancias el anticuerpo sufre una
modificacin en su segundo segmento
C5b SE UNE A
C6 Y C7
C6
C5b67 SE UNE A
LA MEMBRANA VIA
C7
COMPLEJO
C5b67
C7
C5b
PATOGENO
MAC
C8 SE UNE AL
COMPLEJO Y SE
INSERTA EN
LA MEMBRANA
C8
POR ULTIMO C9
SE UNE AL COMPLEJO
Y SE
POLIMERIZA
C9
MAC
10-16
MOLECULAS DE C9
Hasta 15 molculas de C9
SE UNEN PARA FORMAR
pueden polimerizarse para
UN PORO EN LA
formar el poro
MEMBRANA
ESQUEMA
DEL PORO DE COMPLEJO
DE ATAQUE A
MEMBRANA(MAC)
Fig 4 En esta secuencia de figuras se muestra la fase ltica en la que se forma el complejo de
ataque de membrana CAM.
VIA CLSICA
VIA ALTERNA
Activador
Ag:Ac
Ca++ C1q (r,s)
C4
C3b
Mg++
Mg++
C2
C3bB
Properdina (P)
Factor D
C4b2a
C3bBb(P)
C3
C3
C3b2Bb (P)
C4b2a3b
C5
C3 convertasa
C5 convertasa
IgA humana
Polisacrido
microbiano
Endotoxina
Factor B
C5b+C6+C7+C8 + C9(n)
Activation of the classical, lectin and alternative pathways. a | The classical pathway is initiated by the
binding of the C1 complex to antibodies that are bound to antigens on the surface of bacteria. The C1
complex consists of C1q and two molecules each of C1r and C1s. The binding of the recognition
subcomponent C1q to the Fc portion of immunoglobulins results in autoactivation of the serine protease
C1r. C1r then cleaves and activates C1s, which translates the activation of the C1 complex into
complement activation through the cleavage of C4 and C2 to form a C4bC2a enzyme complex. C4bC2a
acts as a C3 convertase and cleaves C3, which results in products that bind to and cause the destruction of
invading bacteria. b | The lectin pathway is initiated by the binding of either mannose-binding lectin
(MBL) or ficolin associated with MBL-associated serine protease 1 (MASP1), MASP2, MASP3 and
small MBL-associated protein (sMAP) to an array of carbohydrate groups on the surface of a bacterial
cell. Similar to C1s, MASP2 is responsible for the activation of C4 and C2, which leads to the generation
of the same C3 convertase (C4bC2a) as in the classical pathway. MASP1 is able to cleave C3 directly. c |
The alternative pathway is initiated by the low-grade activation of C3 by hydrolysed C3 (C3(H2O)) and
activated factor B (Bb). The activated C3b binds factor B (B), which is then cleaved into Bb by factor D
(D) to form the alternative pathway C3 convertase, C3bBb. Once C3b is attached to the cell surface, the
amplification loop consisting of the alternative-pathway components is activated, and the C3-convertase
enzymes cleave many molecules of C3 to C3b, which bind covalently around the site of complement
activation.
Domain and oligomeric structure of mannosebinding lectin and ficolins. Mannose-binding lectin
(MBL) and ficolins are oligomers of structural
subunits, each of which is composed of three
identical 32-kDa and 35-kDa polypeptides,
respectively. Each subunit contains: an aminoterminal, cysteine-rich region; a collagen-like
domain that consists of tandem repeats of Gly-XaaYaa triplet sequences (where Xaa and Yaa represent
any amino acid); a neck region; and a carboxyterminal carbohydrate-recognition domain (CRD) in
MBL and fibrinogen-like domain in ficolins. MBL
forms several sizes of oligomers15 and the trimeric
form is shown. The tetrameric form of L-ficolin/P35
that is shown here was indicated by electron
microscopy studies
Jules Bordet was born in Soignies, Belgium, on June 13, 1870. Hewas educated in Brussels where he
graduated as Doctor of Medicine in 1892. In 1894 he went to Paris to work at the Pasteur Institute
until 1901 when he returned to Belgium to found the Pasteur Institute, Brussels. He has been Director
of the Belgian Institute since its inception (honorary since 1940) and Professor of Bacteriology,
University of Brussels, since 1907 (honorary since 1935).........................................................................
Bordet's early studies showed that antimicrobic sera include two active substances, one existing before
immunization, known as alexine, and the other a specific antibody created by vaccination: he
developed a method of diagnosing microbes by sera. In 1898, he discovered haemolytic sera and
showed that the mechanism of their action on foreign blood is similar to that by which an antimicrobic
serum acts on microbes and, furthermore, that the reactions of the sera are colloidal in nature. He has
contributed much towards the understanding ofthe formation of coagulin and also anaphylactic
poisons. Together with Gengou (in 1906), he cultivated B.pertussis and laid the foundations of the
generally accepted opinion that this organism is the bacterial cause of whooping cough. In addition to
his being an acknowledged world authority in many branches of bacteriology, Bordet was considered
to be a great exponent and worker on immunology. He was the author of Trait de l'Immunit dans les
Maladies Infectieuses (2nd ed., 1939) (Treatise on immunity in infectious diseases) and a great
number of medical publications.
..........................................................................................
Bordet was a permanent member of the Administrative Council of Brussels University, he was
President of the First International Congress of Microbiology (Paris, 1930), and Past President of the
Premier Council of Hygiene of Belgium, the Scientific Council of the Pasteur Institute of Paris and the
Belgian Academy of Medicine. He was Doctor, honoris causa, of the Universities of Cambridge,
Paris, Strasbourg, Toulouse, Edinburgh, Nancy, Caen, Montpellier, Cairo, Athens, and Quebec. He
was a member of the Belgian Royal Academy, the Royal Society (London), the Royal Society of
Edinburgh, the Academy of Medicine (Paris), the National Academy of Sciences (U.S.A.), and many
other academies and societies. Bordet gained many awards during his career, including the Grand
Cordon de l'Ordre de la Couronne de Belgique (1930), the Grand Cordon de l'Ordre de Lopold
(1937), the Grand Croix de la Lgion d'Honneur (1938), and public honours of Rumania, Sweden and
Luxemburg.
In 1899 Bordet married Marthe Levoz. They had one son, Paul,who succeeded his father as Chief of
the Pasteur Institute in Brussels and also as Professor of Bacteriology, and two daughters. Jules Bordet
died on April 6, 1961.