scholarly journals Immunological and Therapeutic Strategies against Salmonid Cryptobiosis

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Patrick T. K. Woo
Keyword(s):  
Monoclonal Antibody ◽  
Single Dose ◽  
Salvelinus Fontinalis ◽  
Alternative Pathway ◽  
Clinical Signs ◽  
Abdominal Distension ◽  
Therapeutic Strategies ◽  
Brook Charr ◽  
Alternative Pathway Of Complement ◽  
High Parasitaemias

Salmonid cryptobiosis is caused by the haemoflagellate,Cryptobia salmositica. Clinical signs of the disease in salmon (Oncorhynchusspp.) include exophthalmia, general oedema, abdominal distension with ascites, anaemia, and anorexia. The disease-causing factor is a metalloprotease and the monoclonal antibody (mAb-001) against it is therapeutic. MAb-001 does not fix complement but agglutinates the parasite. Some brook charr,Salvelinus fontinaliscannot be infected (Cryptobia-resistant); this resistance is controlled by a dominant Mendelian locus and is inherited. InCryptobia-resistant charr the pathogen is lysed via the Alternative Pathway of Complement Activation. However, some charr can be infected and they have high parasitaemias with no disease (Cryptobia-tolerant). In infectedCryptobia-tolerant charr the metalloprotease is neutralized by a natural antiprotease,α2 macroglobulin. Two vaccines have been developed. A single dose of the attenuated vaccine protects 100% of salmonids (juveniles and adults) for at least 24 months. Complement fixing antibody production and cell-mediated response in vaccinated fish rise significantly after challenge. Fish injected with the DNA vaccine initially have slight anaemias but they recover and have agglutinating antibodies. On challenge, DNA-vaccinated fish have lower parasitaemias, delayed peak parasitaemias and faster recoveries. Isometamidium chloride is therapeutic against the pathogen and its effectiveness is increased after conjugation to antibodies.

Hematin Promotes Complement Alternative Pathway-Mediated Deposition of C3 Activation Fragments on Human Erythrocytes: Potential Implications for the Pathogenesis of Anemia in Malaria.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 839-839
Author(s):  
Ronald P. Taylor ◽  
Andrew W. Pawluczkowycz ◽  
Margaret A. Lindorfer ◽  
John W. Waitumbi
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
Alternative Pathway ◽  
Complement Alternative Pathway ◽  
Western Blots ◽  
Marginal Zone B Cells ◽  
Immune Adherence ◽  
Alternative Pathway Of Complement ◽  
Childhood Malaria ◽  
Covalently Bound

Abstract Childhood malaria caused by Plasmodium falciparum (pf) is often characterized by severe anemia at low parasite burdens; the mechanism(s) responsible for this pathology remain to be defined. We have reported that erythrocyte (E) CR1, the immune adherence receptor specific for C3b, is reduced during anemia in childhood malaria, suggesting a possible role for complement in E destruction. Intravascular lysis of infected E by pf leads to release of E breakdown products hemoglobin and hematin, which have inflammatory properties. Free hematin can bind to E, and we find that in serum and in whole blood anti-coagulated with lepirudin, moderate concentrations of hematin activate the alternative pathway of complement and promote deposition of C3 activation and breakdown products on E. We documented C3 deposition by flow cytometry, and additional fluorescence microscopy studies revealed that most of the deposited C3 fragments are located in close juxtaposition to CR1. Western blots confirmed that the C3 fragments are indeed covalently bound to the E, and immunoprecipitation experiments indicated that a fraction of the deposited C3 is covalently bound to CR1. The degree of C3 fragment deposition is directly correlated with E CR1 levels, both within a given donor’s E population and when E from different donors are compared. E opsonized with complement in the presence of hematin form rosettes with Raji cells, through interaction with CR2, the C3dg receptor expressed on several types of B cells including splenic marginal zone B cells. Thus, hematin-mediated complement activation and C3 fragment deposition on E may promote accelerated splenic (or liver) clearance of the youngest E, which have the most CR1, leading to sudden onset of anemia along with reduction of mean CR1 on surviving E. A monoclonal antibody specific for C3b, mAb 3E7, previously demonstrated to inhibit the alternative pathway of complement, completely blocks the C3 fragment deposition reaction. Use of this monoclonal antibody in non-human primate models of malaria may provide insight into mechanisms of erythrocyte destruction and thus aid in the development of therapies based on inhibiting the alternative pathway of complement.

A novel approach to preventing the hemolysis of paroxysmal nocturnal hemoglobinuria: both complement-mediated cytolysis and C3 deposition are blocked by a monoclonal antibody specific for the alternative pathway of complement

Blood ◽  
2010 ◽  
Vol 115 (11) ◽  
pp. 2283-2291 ◽  
Author(s):  
Margaret A. Lindorfer ◽  
Andrew W. Pawluczkowycz ◽  
Elizabeth M. Peek ◽  
Kimberly Hickman ◽  
Ronald P. Taylor ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Significant Proportion ◽  
Complement C3 ◽  
Classical Pathway ◽  
Immune Functions ◽  
Intravascular Hemolysis ◽  
Alternative Pathway Of Complement

Abstract The clinical hallmark of paroxysmal nocturnal hemoglobinuria (PNH) is chronic intravascular hemolysis that is a consequence of unregulated activation of the alternative pathway of complement (APC). Intravascular hemolysis can be inhibited in patients by treatment with eculizumab, a monoclonal antibody that binds complement C5 thereby preventing formation of the cytolytic membrane attack complex of complement. However, in essentially all patients treated with eculizumab, persistent anemia, reticulocytosis, and biochemical evidence of hemolysis are observed; and in a significant proportion, their PNH erythrocytes become opsonized with complement C3. These observations suggest that PNH patients treated with eculizumab are left with clinically significant immune-mediated hemolytic anemia because the antibody does not block APC activation. With a goal of improving PNH therapy, we characterized the activity of anti-C3b/iC3b monoclonal antibody 3E7 in an in vitro model of APC-mediated hemolysis. We show that 3E7 and its chimeric-deimmunized derivative H17 block both hemolysis and C3 deposition on PNH erythrocytes. The antibody is specific for the APC C3/C5 convertase because classical pathway–mediated hemolysis is unaffected by 3E7/H17. These findings suggest an approach to PNH treatment in which both intravascular and extravascular hemolysis can be inhibited while preserving important immune functions of the classical pathway of complement.

Recruitment of properdin by bi-specific nanobodies activates the alternative pathway of complement

2020 ◽  
Vol 124 ◽  
pp. 200-210 ◽  
Author(s):  
Dennis V. Pedersen ◽  
Thies Rösner ◽  
Annette G. Hansen ◽  
Kasper R. Andersen ◽  
Steffen Thiel ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Alternative Pathway Of Complement

Bénéfices à court terme des mouvements anadromes saisonniers pour une population d'omble de fontaine (Salvelinus fontinalis) du Nouveau Québec

1991 ◽  
Vol 48 (11) ◽  
pp. 2212-2222 ◽  
Author(s):  
Jean-François Doyon ◽  
Christiane Hudon ◽  
Roderick Morin ◽  
F. G. Whoriskey Jr.
Keyword(s):  
Water Level ◽  
Egg Size ◽  
Salvelinus Fontinalis ◽  
Condition Factor ◽  
Size At Maturity ◽  
Brook Charr ◽  
Tissue Water Content ◽  
Tissue Water ◽  
Single Population ◽  
Energetic Reserves

This study characterizes the seasonal anadromous movements of a brook charr population and compares its biological and energetic characteristics with charr spending summer in freshwaters. Downstream movements monitored at a counting fence over 3 yr were most intense in spring but occurred until fall and were positively correlated with rapid increases of water level. The timing of movements varied from year to year. Smaller charr were most subject to being swept downstream compared with freshwater residents, and most trout were concentrated near the mouth of the river. These patterns suggest that the downstream movements of charr in this system are passive. Upstream migrants had a higher condition factor and a lower tissue water content than freshwater residents, indicating that downstream movements result in a faster accumulation of energetic reserves during summer. However, the fortuitous character of anadromous migrations as well as the absence of differences in the biological characteristics (growth, size at maturity, fecundity, egg size) suggests that anadromous and resident fish belong to a single population whose yearly migrant component could be randomly determined.

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