scholarly journals The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus.

1980 ◽  
Vol 151 (5) ◽  
pp. 1275-1287 ◽  
Author(s):  
M S Edwards ◽  
A Nicholson-Weller ◽  
C J Baker ◽  
D L Kasper
Keyword(s):  
Sialic Acid ◽  
Specific Antibody ◽  
Alternative Pathway ◽  
Group B Streptococcus ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Pathway Activation ◽  
Alternative Complement ◽  
Group B

The native capsular polysaccharide antigen of type III, group B Streptococcus contains a terminal sialic acid residue on each repeating unit that masks all end-group galactopyranose residues and prevents alternative pathway complement activation by adult human sera in the absence of type-specific antibody. The critical role of the sialic acid residues in allowing the organism to evade activating the alternative complement pathway was shown when neuraminidase treatment of the organism converted the bacteria to activators of the alternative pathway as assessed in agammaglobulinemic serum. The requirement for specific antibody in permitting alternative pathway activation by the fully sialated bacteria was shown when sera that contained low levels of specific antibody failed to activate this pathway, and when prior absorption of serum that contained higher type-specific antibody levels with the capsular antigen failed to activate this pathway. The use of C2-deficient sera showed that the calssical pathway was not required for antibody-dependent alternative pathway activation. The use of isotonic, pH 7.5, veronal-NaCl buffer that contained 1% gelatin and that was supplemented to 4 mM Mg++ and 16 mM EGTA and adjusted to pH 7.5 (MgEGTA) ruled out the participation of the C1-bypass pathway. The presence of sialic acid on the bacterial surface is one means of evading an important mechanism of natural immunity, namely activation of complement by the alternative pathway. Only specific antibody, i.e., acquired immunity, can overcome this virulence factor.

scholarly journals Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes.

1982 ◽  
Vol 155 (1) ◽  
pp. 231-247 ◽  
Author(s):  
G Pfaffenbach ◽  
M E Lamm ◽  
I Gigli
Keyword(s):  
Guinea Pig ◽  
Immune Complexes ◽  
Alternative Pathway ◽  
Fluid Phase ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Myeloma Protein ◽  
Pathway Activation ◽  
Alternative Complement ◽  
Iga Immune Complexes

Activation of the complement system by IgA was investigated with immune complexes containing a mouse IgA myeloma protein with specificity for phosphorylcholine linked to bovine serum albumin (PC-BSA). These IgA anti-PC-BSA immune complexes activated the alternative complement pathway in mouse and guinea pig serum, while human complement was not affected. The activation proceeded with consumption of C3 but little or no consumption of C5. C3 did not bind to the IgA immune complexes during complement activation although it did bind covalently to IgG immune complexes. It is suggested that IgA immune complexes do not supply a suitable surface for C3 binding and effective alternative pathway convertase assembly; therefore, cleavage is limited and occurs primarily in the fluid phase. Without C3 binding, C5 cleavage does not occur nor can the alternative pathway activation proceed to the amplification step.

scholarly journals Capsular Sialic Acid Limits C5a Production on Type III Group B Streptococci

1999 ◽  
Vol 67 (4) ◽  
pp. 1866-1870 ◽  
Author(s):  
Shinji Takahashi ◽  
Youko Aoyagi ◽  
Elisabeth E. Adderson ◽  
Yoshiyuki Okuwaki ◽  
John F. Bohnsack
Keyword(s):  
Sialic Acid ◽  
Specific Antibody ◽  
Acid Content ◽  
Alternative Pathway ◽  
Group B Streptococcus ◽  
Neonatal Infections ◽  
Group B Streptococci ◽  
Sialic Acid Content ◽  
Type Iii ◽  
Group B

ABSTRACT The majority of type III group B streptococcus (GBS) human neonatal infections are caused by a genetically related subgroup called III-3. We have proposed that a bacterial enzyme, C5a-ase, contributes to the pathogenesis of neonatal infections with GBS by rapidly inactivating C5a, a potent pro-inflammatory molecule, but many III-3 strains do not express C5a-ase. The amount of C5a produced in serum following incubation with representative type III strains was quantitated in order to better understand the relationship between C5a production and C5a-ase expression. C5a production following incubation of bacteria with serum depleted of antibody to the bacterial surface was inversely proportional to the sialic acid content of the bacterial capsule, with the more heavily sialylated III-3 strains generating less C5a than the less-virulent, less-sialylated III-2 strains. The amount of C5a produced correlated significantly with C3 deposition on each bacterial strain. Repletion with type-specific antibody caused increased C3b deposition and C5a production through alternative pathway activation, but C5a was functionally inactivated by strains that expressed C5a-ase. The increased virulence of III-3 strains compared to that of III-2 strains results at least partially from the higher sialic acid content of III-3 strains, which inhibits both opsonophagocytic killing and C5a production in the absence of type-specific antibody. We propose that C5a-ase is not necessary for III-3 strains to cause invasive disease because the high sialic acid content of III-3 strains inhibits C5a production.

Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway

1997 ◽  
Vol 83 (4) ◽  
pp. 1090-1095 ◽  
Author(s):  
Martin R. Weiser ◽  
Taine T. V. Pechet ◽  
Julian P. Williams ◽  
Minghe Ma ◽  
Paul S. Frenette ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Alternative Pathway ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Acid Aspiration ◽  
Airway Injury ◽  
Distal Airway ◽  
Alternative Complement

Weiser, Martin R., Taine T. V. Pechet, Julian P. Williams, Minghe Ma, Paul S. Frenette, Francis D. Moore, Lester Kobzik, Richard O. Hines, Denisa D. Wagner, Michael C. Carroll, and Herbert B. Hechtman. Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway. J. Appl. Physiol. 83(4): 1090–1095, 1997.—Acid aspiration may result in the development of the acute respiratory distress syndrome, an event associated with significant morbidity and mortality. Although once attributed to direct distal airway injury, the pulmonary failure after acid aspiration is more complex and involves an inflammatory injury mediated by complement (C) and polymorphonuclear leukocytes. This study examines the injurious inflammatory cascades that are activated after acid aspiration. The role of neutrophils was defined by immunodepletion before aspiration, which reduced injury by 59%. The injury was not modified in either P- or E-selectin-knockout mice, indicating that these adhesion molecules were not operative. C activation after aspiration was documented with immunochemistry by C3 deposition on injured alveolar pneumocytes. Animals in which C activation was inhibited with soluble C receptor type 1 (sCR1) had a 54% reduction in injury, similar to the level of protection seen in C3-knockout mice (58%). However C4-knockout mice were not protected from injury, indicating that C activation is mediated by the alternative pathway. Finally, an additive effect of neutrophils and C was demonstrated whereby neutropenic animals that were treated with sCR1 showed an 85% reduction in injury. Thus acid aspiration injury is mediated by neutrophils and the alternative C pathway.

scholarly journals Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway

2019 ◽  
Vol 203 (6) ◽  
pp. 1411-1416 ◽  
Author(s):  
Manabu Hayashi ◽  
Takeshi Machida ◽  
Yumi Ishida ◽  
Yusuke Ogata ◽  
Tomoko Omori ◽  
...  
Keyword(s):  
Cutting Edge ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Alternative Complement
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