Antibody-Based Modulation of Humoral Immune Responses in Adults and Infants 公开
Goins, Chelsey (2010)
Published
Abstract
Antibodies have powerful stimulatory abilities, particularly
when combined with
specific antigen in the form of immune complexes (ICs). These
complexes can activate
immune responses in such a way as to enhance both the speed and the
magnitude of the
response. Here we examine two instances in which ICs enhance
humoral immune
responses.
The reigning paradigm of immunologic memory has long been that
secondary
antibody responses are derived from memory B cells. However, this
model lacks the
flexibility necessary to survive in an ever-evolving world. We
examined the origins of
the secondary response, and in particular the role of ICs. ICs are
formed naturally upon
secondary antigen encounter, making them of particular interest in
examining B cell
activation at this time. We found that naïve B cells
participate heavily in the secondary
antibody response. This participation is mediated by ICs acting
through Fc receptors.
While antibodies can be stimulatory, there are also instances of
antibodies
suppressing immune responses. This is particularly true in the case
of maternally derived
antibodies in newborns, which protect infants from infection during
the early months of
life but inhibit their ability to form antibody responses of their
own. Since maternal
antibodies are primarily IgG, which is known to suppress responses
to particulate antigen
while enhancing responses to soluble antigen, we investigated the
effect of different
immunogens on the infant immune response in the presence and
absence of maternal
antibodies. We found that maternal antibodies were able to enhance
antibody responses
to soluble antigens only. This enhanced response is short-lived, as
maternal antibodies
appear to block the formation of B cell memory, regardless of
antigen type.
Responses in Adults and Infants
By
Chelsey L. Goins
B.S., Saint Louis University, 2005
Advisor: Joshy Jacob, Ph.D.
A dissertation submitted to the Faculty of the James T. Laney
School of Graduate Studies
of Emory University in partial fulfillment of the requirements for
the degree of Doctor of
Philosophy
Program in Immunology and Molecular Pathogenesis
Graduate Division of Biological and Biomedical Sciences
2010
Table of Contents
Chapter 1:
Development and transfer of humoral immunity 1
Immunologic memory and vaccination 2
Formation of B cell memory 4
- Primary antigen encounter 4
- Germinal center reactions 6
- B cell memory 9
- Secondary antibody responses 11
- Immune complex mediated B cell activation 15
Maternally derived antibodies 18
- The infant immune system 19
- Transfer of maternal antibody 21
- Maternal suppression of infant immune responses 25
Chapter 2:
Immune complex-mediated enhancement of
secondary antibody responses 29
Abstract 30
Introduction 31
Materials and Methods 34
Results 37
Discussion 44
Figure Legends 47
Figures 51
Chapter 3:
Maternal antibodies enhance infant B cell responses to
soluble antigen but block the formation of memory 57
Abstract 58
Introduction 59
Materials and Methods 61
Results 64
Discussion 69
Figure Legends 73
Figures 76
Chapter 4:
Discussion 82
Introduction 83
Fate of antibody-activated B cells 85
IgM immune complexes 90
Effects of maternal antibody on memory formation 92
References 95
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