Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-3-20
pubmed:abstractText
Despite a century of study, the relationship between Ag-specific Ig concentration and protection remains poorly understood for the majority of pathogens. In certain conditions, administration of high Ab doses before challenge with an infectious agent can be less effective than smaller Ab doses, a phenomenon which is consistent with a prozone-like effect. In this study, the relationship between IgG1, IgG2a, IgG2b, and IgG3 dose, infective inocula, and protection was investigated in a mouse model of Cryptococcus neoformans infection. The activity of each IgG subclass ranged from protective to disease-enhancing depending on both the Ab dose and infective inocula used. Enhanced dissemination to the brain was observed in mice given a high IgG2a dose and a relatively low inoculum. Ab administration had immunomodulatory effects, with cytokine expression in lung, brain, and spleen varying as a function of the infective inoculum Ab dose and IgG subclass. In vitro studies did not predict or explain the mechanism of in vivo prozone-like effects, because all isotypes were opsonic and elicited NO release from macrophages. IgG2a was most efficient in inducing a macrophage oxidative burst. These results reveal that an individual Ab can be protective, nonprotective, or disease-enhancing depending on its concentration relative to a challenge inoculum. Our findings have implications for the potential contribution of Ab responses to defense against microbial diseases because Ab-mediated immunity may be protective, nonprotective, or even deleterious to the host.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3621-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12646626-Animals, pubmed-meshheading:12646626-Antibodies, Monoclonal, pubmed-meshheading:12646626-Cell Line, pubmed-meshheading:12646626-Chemokines, pubmed-meshheading:12646626-Colony Count, Microbial, pubmed-meshheading:12646626-Complement System Proteins, pubmed-meshheading:12646626-Cryptococcosis, pubmed-meshheading:12646626-Cryptococcus neoformans, pubmed-meshheading:12646626-Cytokines, pubmed-meshheading:12646626-Dose-Response Relationship, Immunologic, pubmed-meshheading:12646626-Drug Administration Schedule, pubmed-meshheading:12646626-Immunization, Passive, pubmed-meshheading:12646626-Immunoglobulin G, pubmed-meshheading:12646626-Immunoglobulin Isotypes, pubmed-meshheading:12646626-Injections, Intraperitoneal, pubmed-meshheading:12646626-Macrophages, Peritoneal, pubmed-meshheading:12646626-Male, pubmed-meshheading:12646626-Mice, pubmed-meshheading:12646626-Mice, Inbred A, pubmed-meshheading:12646626-Nitrites, pubmed-meshheading:12646626-Organ Specificity, pubmed-meshheading:12646626-Phagocytosis, pubmed-meshheading:12646626-Respiratory Burst, pubmed-meshheading:12646626-Survival Analysis
pubmed:year
2003
pubmed:articleTitle
More is not necessarily better: prozone-like effects in passive immunization with IgG.
pubmed:affiliation
Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.