Antibody-mediated Clearance of Bordetella Species

Open Access
Author:
Kirimanjeswara, Girish Soorappa
Graduate Program:
Pathobiology
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
November 19, 2004
Committee Members:
  • Eric Thomas Harvill, Committee Chair
  • Mary J Kennett, Committee Chair
  • Biao He, Committee Member
  • Avery August, Committee Member
  • Sarah Ellen Ades, Committee Member
Keywords:
  • complemenet
  • pertussis
  • passive transfer
  • antibodies
  • bordetella
  • Fc receptors
  • TLRs
Abstract:
This doctoral dissertation work focused on examining the contribution of mucosal and serum antibodies to sterilizing immunity against the respiratory pathogens, B. bronchiseptica and B. pertussis. During the course of the investigation, we discovered that the mechanism of antibody-mediated clearance of these closely related subspecies of Bordetella differ significantly. Adoptively transferred serum antibodies cleared the animal pathogen B. bronchiseptica within three days of infection. Antibodies, however, had a minimal effect on human adapted B. pertussis until after the generation of a Th1 response. Comparative immunobiology of these two subspecies in a mouse model revealed that B. pertussis is initially able to resist antibody-mediated clearance via the expression of pertussis toxin, which modulates the critical immune responses required for this rapid bacterial elimination. This suggests a model in which B. pertussis is able to transiently infect immune individuals and persist in vaccinated populations. This model is supported by epidemiological data indicating frequent epidemics of whooping coughs in highly vaccinated populations. Additionally, this study revealed distinct yet overlapping immune surveillance mechanisms in different areas of the respiratory tract. Together, this study provides important insights into the evolution, adaptation, and epidemiology of B. pertussis. It also aids in developing novel prophylactic and therapeutic strategies for whooping cough. Above all, it makes substantial contributions to the respiratory immunology.