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More is not necessarily better: prozone-like effects in passive immunization with IgG
Carlos P Taborda1, Johanna Rivera, Oscar Zaragoza
1Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 21, 2003
Summary
Antibody (Ab) concentration impacts protection against Cryptococcus neoformans infection. High doses can be less effective than low doses, with varying effects depending on Ab levels and pathogen load.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- The relationship between antibody (Ab) concentration and protection against pathogens is not fully understood.
- High Ab doses can sometimes be less effective than lower doses, suggesting a prozone-like effect.
Purpose of the Study:
- To investigate the dose-dependent relationship between specific IgG subclasses (IgG1, IgG2a, IgG2b, IgG3), inoculum size, and protection against Cryptococcus neoformans infection in a mouse model.
- To explore the immunomodulatory effects of Ab administration on cytokine expression.
- To assess the predictive value of in vitro assays for in vivo Ab activity.
Main Methods:
- Mice were infected with varying inocula of Cryptococcus neoformans and treated with different doses of specific IgG subclasses.
- Cytokine expression in lung, brain, and spleen was analyzed.
- In vitro assays were performed to evaluate Ab opsonic activity and effects on macrophage responses (NO release, oxidative burst).
Main Results:
- The protective or disease-enhancing activity of each IgG subclass varied with both Ab dose and inoculum size.
- High IgG2a doses combined with low inocula led to enhanced dissemination to the brain.
- Ab administration modulated cytokine expression in a dose- and subclass-dependent manner.
- In vitro studies showed all isotypes were opsonic and induced NO release, with IgG2a being most efficient in inducing macrophage oxidative burst, but did not fully explain in vivo prozone-like effects.
Conclusions:
- Antibody-mediated immunity can be protective, nonprotective, or even detrimental depending on the antibody concentration relative to the pathogen challenge.
- The concentration of specific antibodies and the infectious inoculum are critical factors determining the outcome of Ab-mediated immunity.
- Findings highlight the complexity of Ab-mediated defense against microbial diseases and have implications for vaccine and immunotherapy development.