Trends in Immunology
Volume 24, Issue 9, September 2003, Pages 474-478
Journal home page for Trends in Immunology

Antibody-mediated regulation of cellular immunity and the inflammatory response

https://doi.org/10.1016/S1471-4906(03)00228-XGet rights and content

Abstract

For many pathogens the role of antibody-mediated immunity (AMI) is poorly understood, in part because of the limited tools available to establish antibody efficacy. AMI is classically associated with opsonization, toxin and viral neutralization, complement fixation and antibody-dependent cellular cytotoxicity. However, recent studies indicate new functions for AMI ranging from direct antimicrobial action to modulation of the inflammatory response. The efficacy of AMI against some pathogens is dependent on cell-mediated immunity. A new interpretation of the role of AMI is proposed whereby it is in proinflammatory the early stages of infection and anti-inflammatory at later stages of the host–microbe interaction and in the setting of established immunity and/or in an immune individual.

Section snippets

Interactive Abs: interdependence of AMI and CMI

The historically recognized, or classical, mechanisms of Ab action include toxin neutralization, viral neutralization, opsonization and Ab-dependent cellular cytotoxicity (ADCC). Toxin and viral neutralization are singular Ab functions because Ab can mediate these without additional mediators and/or cells. Classical mechanisms of Ab action that are not singular include opsonization, ADCC and in some instances, complement activation. These functions are termed ‘interactive’ because they require

Ab can either enhance or reduce inflammation

Potential mechanisms for interaction and/or collaboration between AMI and CMI can be inferred from available knowledge about the host response to microbial agents and the functions of Ab and T cells. Cytokines and chemokines can influence many facets of the immune response, including the generation of an effective inflammatory response and the functioning of immune cells. Nitric oxide (NO) can function directly as an antimicrobial effector molecule or indirectly through regulatory effects on

Ab and B cells modulate the inflammatory response

The enhanced susceptibility of B-cell deficient mice to West Nile virus [35], Chlamydiohia abortus [36], Leishmania donovani [37], Toxoplasma gondii [38] and HSV [39] is associated with more intense inflammation and/or proinflammatory cytokine response. HSV infection in B-cell deficient mice is associated with activation of Th1- and reduced Th2-type CD4+ T-cell cytokine responses [39] but specific Ab protection in mice with lymphocytic choriomeningitis is associated with a reduction in

Good responses reduce and bad responses cause damage

Ab responses are generally thought to be beneficial, however, examples of disease-enhancing Abs to viral pathogens have been known for some time. In recent years, studies with mAbs to C. neoformans have provided a glimpse into the intricacy of what might constitute a protective (‘good’) or a non-protective or disease-enhancing (‘bad’) Ab response. The efficacy of a mAb against C. neoformans is dependent on Ig-related variables, such as specificity [49], IgG subclass and amount [50] and host

Conclusion

Classical views of Ab function are too limited to account for the potential effects of AMI on the immune response and the host–microbe interaction, particularly for microbes that only cause host damage in the setting of impaired immunity. Studies with mAbs have revealed that the efficacy of the immune response to infection can reflect the interactions between AMI and CMI, and in doing so have debunked the view of a division of labour, whereby AMI and CMI are limited to defence against

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