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Humoral Immune Response

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While the humoral response to Bordetella pertussis is necessary for clearance of the inhabiting pathogen, it does not appear to compose the dominant response to a natural primary infection.  B cell deficient mice are not able to clear respiratory infections of pertussis (Kirimanjeswara et al. 2002).  It has been found that disruption of the Ig-µ chain decreases the ability of the organism to remove an infection (Mills et al. 1998).  Reconstitution of B cell deficient mice with transferred antibodies leads to the subsequent removal of the pathogen (Kirimanjeswara et al. 2002).  Experimentation has revealed that rapidity of bacterial clearance does not correlate with antibody titer (Leef et al. 2000).  It has been suggested that pertussis resists clearance by antibodies, albeit it by an unknown mechanism (Kirimanjeswara et al. 2002).  This position is supported by the ability of pertussis to survive and spread even within developed, vaccinated populations.  The success of immunization (both whole cell and acellular), however, suggests that B cells can be utilized as part of an effective, fully orchestrated response against Bordetella pertussis and its toxins.  Some other effects (beside antibody production) of B cell have been suggested: presentation to T cells, cytokine and chemokine production, and interaction with macrophages and NK cells (Leef et al. 2000).
           

Humoral response to Bordetella pertussis does appear to include IgG, IgA, and IgE (Ryan et al. 1998).  The location of pertussis infections in the mucosa of the respiratory tract supports these findings.  These three isotypes are small and able to diffuse into tissue and extracellular spaces (Janeway et al. 2005).  It has been shown that immunoglobulins (IgG and IgA) specific for Bordetella are able to induce phagocytosis, respiratory burst, and bacterial killing (Rodriguez and van der Pol 2003). 
Importantly, IgG and IgA are known as neutralizing antibodies towards bacterial toxins (Janeway et al. 2005).  Bordetella pertussis produces a number of bacterial toxins, including pertussis toxin (PT).  Pertussis toxin is known to increase amounts of circulating IgG, IgA, and IgE.  Moreover, the expression of IL-1 (by macrophages), B7 (by macrophages and B cells), and CD28 (by T cells) are increased in the presence of PT.  IL-1 plays a role in stimulating TH2 cells, which in turn can activate B cells to differentiate into plasma cells (Ryan et al. 1998).  High titers of antibodies against PT are produced in an immune response to Bordetella pertussis (Ryan et al. 1998).

The adjuvant activity of detoxified versions of other bacterial toxins specific to pertussis infections indicates the role of humoral immunity in neutralizing and removing elements of infection other than PT.  Filamentous hemagglutinin (FHA) and pertactin (PRN), along with PT, are used as components of vaccines against Bordetella pertussis.  Studies of the immune response to these vaccines identify anti-PRN immunoglobulins (Poolman and Hallander 2007).  Thus, it appears that antibody response to bacterial toxins may play an important role in immunity, at least in secondary responses and beyond.
Lastly, the Fcγ receptor is required for clearance of an infection by Bordetella pertussis (Wolfe et al. 2005).  This receptor for IgG constant region suggests that phagocytosis of bacterial components is mediated by antibodies to some extent.  At the same time, clearance of pertussis requires T cells and neutrophils in addition of a humoral response (Wolfe et al. 2005).  Thus, the antibody response is necessary but not sufficient protection to infection by Bordetella pertussis.

 

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