Insights into mechanisms of antibody-mediated immunity from studies with Cryptococcus neoformans

A. Casadevall, Liise-anne Pirofski

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

At first glance Cryptococcus neoformans appears an unlikely microbe to provide a new understanding of mechanisms of antibody-mediated immunity (AMI), because it is a facultative intracellular fungal pathogen for which the role of naturally acquired AMI in host defense is uncertain. However, numerous studies have now established that certain antibodies (Abs) against C. neoformans are protective in certain hosts. Studies with Abs to C. neoformans have provided new insights into AMI and generated new precedents with implications for other pathogens. The following concepts have emerged: 1) susceptibility to C. neoformans may be related to qualitative and quantitative aspects of the Ab response; 2) protective monoclonal Abs can be generated against pathogens even when the role of humoral immunity is uncertain; 3) Abs to C. neoformans mediate protection by immunomodulatory effects, thereby linking Ab efficacy to the overall host immune response; 4) Ab efficacy is critically dependent on fine specificity, which in turn is affected by immunoglobulin variable region usage, somatic mutation and constant region usage; 5) the efficacy of passive Ab therapy is a function of Ab dose and infecting innoculum, with lack of efficacy at the extremes of Ab concentration; 6) Ab-mediated toxicity resulting from antigen-Ab complex-induced release of platelet activating factor is isotype dependent. Observations with C. neoformans have stimulated a reappraisal of the role of humoral immunity for other pathogens and highlighted the limitations in current methods of assessing the role of Ab in host defense.

Original languageEnglish (US)
Pages (from-to)421-433
Number of pages13
JournalCurrent Molecular Medicine
Volume5
Issue number4
DOIs
StatePublished - Jun 2005

Fingerprint

Cryptococcus neoformans
Immunity
Pathogens
Antibodies
Humoral Immunity
Immunoglobulin Variable Region
Platelet Activating Factor
Toxicity
Monoclonal Antibodies
Antigens
Mutation

Keywords

  • Antibody-mediated immunity
  • Cryptococcus neoformans
  • Glucuronoxylomannan
  • Immunomodulation
  • Isotypes
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

Insights into mechanisms of antibody-mediated immunity from studies with Cryptococcus neoformans. / Casadevall, A.; Pirofski, Liise-anne.

In: Current Molecular Medicine, Vol. 5, No. 4, 06.2005, p. 421-433.

Research output: Contribution to journalArticle

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