Mucosal Immune Defense: Immunoglobulin A

446 Pages·2007·5.03 MB·English

by  Charlotte S. Kaetzel

Mucosal Immune Defense:
Immunoglobulin A
Mucosal Immune
Defense:
Immunoglobulin A
Edited by
Charlotte Slayton Kaetzel
Professor of Microbiology, Immunology and Molecular Genetics
University of Kentucky, Lexington, Kentucky
Charlotte S. Kaetzel
Department of Microbiology
Immunology and Molecular Genetics
University of Kentucky
Lexington, KY 40536
USA
[email protected]
ISBN-13: 978-0-387-72231-3 e-ISBN-13: 978-0-387-72232-0
Library of Congress Control Number: 2007934987
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Preface
Although the existence of a humoral “immune” system has been appreciated
for millennia, it was not until 1890 that “antibodies” were identified as serum
proteins capable of recognizing and neutralizing antigens with a high degree
of specificity (von Behring and Kitasato, 1890). Nearly 50 years later, the
advent of physicochemical techniques for analyzing the size and charge of
serum proteins led to the proposal that antibodies comprised multiple
isotypes (Tiselius and Kabat, 1939). The pioneering work of Heremans and
colleagues (Carbonara and Heremans, 1963; Heremans, 1959; Heremans et
al., 1959, 1963) demonstrated that a carbohydrate-rich antibody species found
in the β-globulin fraction of human serum was distinct from the previously
identified IgG and IgM isotypes; this new form of antibody was subsequently
designated “IgA”. Shortly thereafter, Tomasi and Zigelbaum (1963) demon-
strated that IgA in external secretions, unlike serum IgA, consisted mainly
of dimers of the basic immunoglobulin subunit. Further structural studies
revealed that the IgA dimers in SIgA were linked to an additional glycoprotein
of about 80 kDa, which was originally designated the “secretory piece” and
is now called the secretory component (SC) (Tomasi et al., 1965). Because
most of the serum IgA is monomeric, the question arose whether IgA dimers
in SIgA were assembled from serum-derived monomeric IgA or were derived
from locally synthesized dimeric IgA. Two landmark experiments demon-
strated that the IgA in colostrum is synthesized by local plasma cells as an
11S dimer. Lawton and Mage (1969) examined the distribution of b locus
light-chain allotypic markers in colostral IgA from heterozygous rabbits. If
the SIgA were assembled from serum-derived monomeric IgA, one would
expect to find a random assortment of the light-chain markers. However,
immunoprecipitation with antiallotypic antibodies revealed that individual
SIgA molecules contained either the b4 or b5 marker, but not both, suggesting
that the IgA dimers were assembled within local plasma cells. Similar results
were obtained by Bienenstock and Strauss (1970), who demonstrated that
individual SIgA molecules from human colostrum contained either κ or λ
light chains, but not both. The concept of local origin of SIgA was upheld
by later studies in which transport of locally synthesized IgA into jejunal
v
vi Preface
secretions (Jonard et al., 1984) and saliva (Kubagawa et al., 1987) was found
to be significantly greater than transport of serum-derived IgA.
Further support for the model of local synthesis of polymeric IgA came
with the discovery of the “joining” (J) chain, a peptide of about 15 kDa that
was found to be a subunit of dimeric IgA and pentameric IgM isolated from
colostrum (Halpern and Koshland, 1970; Mestecky et al., 1971). Subsequent
studies demonstrated that the J-chain was expressed by a high percentage of
IgA- and IgM-secreting plasma cells in mucosal tissues and exocrine glands
(Brandtzaeg, 1974, 1983; Brandtzaeg and Korsrud, 1984; Crago et al., 1984;
Korsrud and Brandtzaeg, 1980; Kutteh et al., 1982; Nagura et al., 1979) and
that expression of the J-chain was correlated with in vitro binding of SC to
immunocytes in tissue sections (Brandtzaeg, 1974, 1983; Brandtzaeg and
Korsrud, 1984). Current evidence suggests that the J-chain is not obligatory
for polymerization of IgA and IgM, rather that the presence of the J-chain is
required for binding of polymeric IgA to SC.
It is now appreciated that IgA is the most abundant immunoglobulin isotype;
its total daily synthesis exceeds that of all other isotypes combined. The
predominance of IgA derives from the continuous production and transport
of SIgA across the vast surfaces of mucosal epithelia, some 300–400 m2 in
adult humans. In fact, it has been estimated that 3 g of SIgA are transported
daily into the intestines of the average adult (Conley and Delacroix, 1987;
Mestecky et al., 1986). SIgA antibodies are the diplomats of the immune
system, with the mission of maintaining homeostasis at mucosal surfaces.
We receive the first members of this diplomatic corps from our mothers, in
the form of SIgA antibodies in breast milk, which serve until our developing
immune system produces its own envoys. SIgA antibodies can be found at
every mucosal surface, where they enlist the aid of epithelial cells and a host
of innate immune factors to negotiate with microbes, food antigens, and
environmental substances. Microbes that agree not to breach the mucosal
barrier and to work for the benefit of the host are welcomed as members of
the commensal microbiota. Pathogens and noxious substances that threaten
to invade the body proper are neutralized and deported through the closest
body orifice. Only when diplomacy fails, because of overwhelming numbers
of enemy combatants, microbial weapons of mass destruction, or defects in
the IgA system, are the big guns of the adaptive immune response (such as
IgG antibodies and effector T-cells) recruited to protect the host. The cost of
the military option is collateral damage to the mucosal surface, with the risk
of serious injury and even death. A healthy IgA system allows us to thrive in
a world full of potential pathogens and to co-exist peacefully with hundreds
of billions of commensal microorganisms.
Recent advances in human genomics, gene regulation, structural biology,
cell signaling, and immunobiology have greatly enhanced our understand-
ing of this important class of antibody. This volume is designed to serve
as a reference for current knowledge of the biology of IgA and its role in
mucosal immune defense and homeostasis. Topics include the structure of
Preface vii
IgA (Chapter 1), the development of IgA plasma cells (Chapter 2), epithe-
lial transport of IgA and interaction with Fc receptors (Chapters 3 and 4),
regulation of the IgA system (Chapter 5), biological roles of IgA, including
newly discovered functions (Chapters 6–9), regional functions of IgA (Chap-
ters 10–12), IgA-associated diseases (Chapter 13), and potential therapeutic
applications for IgA (Chapters 14 and 15).
References
Bienenstock, J., and Strauss, H. (1970). Evidence for synthesis of human colostral γA
as an 11S dimer. J. Immunol. 105:274–277.
Brandtzaeg, P. (1974). Presence of J chain in human immunocytes containing various
immunoglobulin classes. Nature 252:418–420.
Brandtzaeg, P. (1983). Immunohistochemical characterization of intracellular J-chain
and binding site for secretory component (SC) in human immunoglobulin
(Ig)-producing cells. Mol. Immunol. 20:941–966.
Brandtzaeg, P., and Korsrud, F. R. (1984). Significance of different J chain profiles in
human tissues: Generation of IgA and IgM with binding site for secretory com-
ponent is related to the J chain expressing capacity of the total local immunocyte
population, including IgG and IgD producing cells, and depends on the clinical
state of the tissue. Clin. Exp. Immunol. 58:709–718.
Carbonara, A. O., and Heremans, J. F. (1963). Subunits of normal and pathological
γ-1A-globulins. (β-2A-globulins). Arch. Biochem. Biophys. 102:137–143.
Conley, M. E., and Delacroix, D. L. (1987). Intravascular and mucosal immunoglobu-
lin A: two separate but related systems of immune defense? Ann. Intern. Med.
106:892–899.
Crago, S. S., Kutteh, W. H., Moro, I., Allansmith, M. R., Radl, J., Haaijman, J. J., and
Mestecky, J. (1984). Distribution of IgA1-, IgA2-, and J chain-containing cells in
human tissues. J. Immunol. 132:16–18.
Halpern, M. S., and Koshland, M. E. (1970). Novel subunit in secretory IgA. Nature
228:1276–1278.
Heremans, J. F. (1959). Immunochemical studies on protein pathology. The immu-
noglobulin concept. Clin. Chim. Acta 4:639–646.
Heremans, J. F., and Schultz, H. E. (1959). Isolation and description of a few properties
of the β2A-globulin of human serum. Clin. Chim. Acta. 4:96–102.
Heremans, J. F., Vaerman, J. P., and Vaerman, C. (1963). Studies on the immune
globulins of human serum. II. A study of the distribution of anti-Brucella and
anti-diphtheria antibody activities among γ-ss, γ-im and γ-1a-globulin fractions.
J Immunol. 91:11–17.
Jonard, P. P., Rambaud, J. C., Vaerman, J. P., Galian, A., and Delacroix, D. L. (1984).
Secretion of immunoglobulins and plasma proteins from the jejunal mucosa.
Transport rate and origin of polymeric immunoglobulin A. J. Clin. Invest. 74:525–535.
Korsrud, F. R., and Brandtzaeg, P. (1980). Quantitative immunohistochemistry of
immunoglobulin- and J-chain-producing cells in human parotid and submandibular
salivary glands. Immunol. 39:129–140.
Kubagawa, H., Bertoli, L. F., Barton, J. C., Koopman, W. J., Mestecky, J., and Cooper,
M. D. (1987). Analysis of paraprotein transport into the saliva by using anti-idiotype
antibodies. J. Immunol. 138:435–439.
viii Preface
Kutteh, W. H., Prince, S. J., and Mestecky, J. (1982). Tissue origins of human polymeric
and monomeric IgA. J. Immunol. 128:990–995.
Lawton, A. R., III, and Mage, R. G. (1969). The synthesis of secretory IgA in the rabbit.
I. Evidence for synthesis as an 11S dimer. J. Immunol. 102:693–697.
Mestecky, J., Russell, M. W., Jackson, S., and Brown, T. A. (1986). The human IgA
system: A reassessment. Clin. Immunol. Immunopath. 40:105–114.
Mestecky, J., Zikan, J., and Butler, W. T. (1971). Immunoglobulin M and secretory
immunoglobulin A: Presence of a common polypeptide chain different from light
chains. Science 171:1163–1165.
Nagura, H., Brandtzaeg, P., Nakane, P. K., and Brown, W. R. (1979). Ultrastructural
localization of J chain in human intestinal mucosa. J. Immunol. 123:1044–1050.
Tiselius, A., and Kabat, E. A. (1939). An electrophoretic study of immune sera and
purified antibody preparations. J. Exp. Med. 69:119–131.
Tomasi, T. B., Jr., Tan, E. M., Solomon, A., and Prendergast, R. A. (1965). Charac-
teristics of an immune system common to certain external secretions. J. Exp. Med.
121:101–124.
Tomasi, T. B., Jr., and Zigelbaum, S. (1963). The selective occurence of γ-1A globulins
in certain body fluids. J Clin. Invest. 42:1552–1560.
von Behring, E., and Kitasato, S. (1890). On the acquisition of immunity against diphtheria
and tetanus in animals. Deutsch. Med. Wochenschr. 16:1145–1148.
Acknowledgments
The Editor gratefully acknowledges the hard work of all of the contributors
to this volume, each of whom is a leader in the field of IgA immunology.
It has been a pleasure to work with such an outstanding group of scien-
tists. I also appreciate the invaluable editorial assistance of my colleague
Dr. Maria Bruno. Finally, I wish to express my sincere thanks to all of the
helpful people at Springer Publishing, especially Andrea Macaluso, who
conceived the concept for this book, Lisa Tenaglia and Suji Prakash.
Charlotte Slayton Kaetzel
Lexington, Kentucky
ix
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
1. The Structure of IgA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Jenny M. Woof
2. IgA Plasma Cell Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Jo Spencer, Laurent Boursier, and Jonathan D. Edgeworth
3. Epithelial Transport of IgA by the Polymeric
Immunoglobulin Receptor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Charlotte S. Kaetzel and Maria E. C. Bruno
4. Fc Receptors for IgA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
H. Craig Morton
5. Regulation of the Mucosal IgA System. . . . . . . . . . . . . . . . . . . . . . . . 111
Finn-Eirik Johansen, Ranveig Braathen,
Else Munthe, Hilde Schjerven, and Per Brandtzaeg
6. Biological Functions of IgA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Michael W. Russell
7. Protection of Mucosal Epithelia by IgA:
Intracellular Neutralization and Excretion of Antigens . . . . . . . . . . . 173
Michael E. Lamm
8. Novel Functions for Mucosal SIgA. . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Armelle Phalipon and Blaise Corthésy
xi