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  • Review Article
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The role of secretory antibodies in infection immunity

Nature Reviews Microbiology volume 8, pages 656–667 (2010)Cite this article

Subjects

Key Points

  • Secretory antibodies (SIgs) have long been recognized as immune effectors that protect mucosal epithelia from infection by pathogens.

  • Recent studies have suggested that this important role is only part of the complex biology of SIgs, and that intracellular neutralization of pathogen determinants within epithelial-cell endosomes may be more important in some infection immunity models than immune exclusion (SIg-mediated blocking of pathogen binding or toxin binding to the epithelial surface).

  • SIgs may also protect the epithelial surface through a phenomenon known as antigen excretion, in which potentially inflammatory antigen in the form of SIg-containing immune complexes is cleared from the subepithelium by the polymeric-immunoglobulin receptor (pIgR).

  • In light of the imperative that is placed on protecting the epithelium from infection in diseases such as HIV/AIDS, and the consequential attempts at mucosal vaccination, it will be important to understand what roles SIgs normally have in maintaining mucosal homeostasis through processes such as T cell regulation and how such processes might be affected by mucosal immunization.

Abstract

The mucosal secretory immune system provides an important primary defence against disease, as studies of humans with mucosal humoral immunodeficiencies suggest that the absence of secretory immunoglobulin A leads to an increase in mucosal infections. However, the infection risks posed do not seem to provide the evolutionary drive to retain constitutive secretion of often 'hard won' protein, suggesting that secretory antibodies may have some other important function (or functions). This Review examines the evidence that secretory antibodies provide an important defence against infection in specific animal models and explores complementary explanations for the evolution of the secretory immune system.

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Figure 1: Polymeric-immunoglobulin receptor-mediated secretion of antibodies.
Figure 2: Induction of immunoglobulin A production in the mouse intestine.
Figure 3: Protection of the mucosal surface by secretory immunoglobulin through immune exclusion, intracellular neutralization or antigen excretion.
Figure 4: Function of the secretory-antibody response in maintaining homeostasis at the mucosal surface during steady state and during infection.

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Acknowledgements

The authors thank all students and staff from the University of Melbourne, Australia, who have contributed to the SIg projects. O.W. is a Career Development Award recipient of the National Health and Medical Research Council (Australia). The authors apologize to those who have contributed to this field but could not be cited.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, VIC, Australia

    Richard A. Strugnell & Odilia L. C. Wijburg

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  1. Richard A. Strugnell
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Correspondence to Richard A. Strugnell.

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DATABASES

Entrez Genome Project

Chlamydia muridarum

Escherichia coli

Giardia lamblia

Salmonella enterica subsp. enterica serovar Typhimurium

Shigella flexneri

Vibrio cholerae

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Glossary

Backpack tumour

Antibody-secreting tumour that is induced by the transfer of antibody-secreting hybridomas to naive animals through subcutaneous injection of the hybridomas in an area of the back.

Antibody avidity

The sum of the affinities of individual Fab–epitope interactions. Dimeric antibodies will have a higher avidity than monomeric antibodies. Antigens with repeating identical epitopes are bound with higher avidity than antigens that carry a single epitope.

Columnar epithelial cell

Differentiated epithelial cell that lines mucosal surfaces, with a column-like appearance and an elongated nucleus. These cells have a lumen-facing ('apical') surface and a tissue facing ('basolateral') surface.

Class switching

Occurs when the activated B cell rearranges the genes encoding the constant region of the antibody molecule that is produced; this rearrangement is usually dependent on cytokines produced by T cells. Hence, a single B cell may produce daughter cells that produce different isotypes (for example, IgG and IgE) of the same antibody specificity. Also known as isotype switching.

Monoassociation

The introduction of a single species, usually a gut flora species, into a germ-free animal.

Complement

Cascade of more than 20 serum glycoproteins that interact to affect some aspects of humoral immunity (for example, lysis of bacteria and opsonization) and which may also drive inflammatory processes such as neutrophil recruitment.

Peyer's patch

Region of differentiated lymphoid tissue found in the lamina propria of the small intestine, containing B cell-rich germinal centres separated by regions containing T cells. The so-called 'dome' epithelium that overlies the Peyer's patch is rich in 'microfold' (M) cells, which sample antigen from the gut for presentation in secondary lymphoid tissues.

B cell antigen-presenting function

In addition to producing antibodies, B cells also express major histocompatiblity complex (MHC) class II molecules and can act as an antigen-presenting cell to CD4+ T cells. In mice such as the μMT/−/− mouse, altered protection might be ascribed to either loss of antibodies or failure of B cells to present antigen to T cells.

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Strugnell, R., Wijburg, O. The role of secretory antibodies in infection immunity. Nat Rev Microbiol 8, 656–667 (2010). https://doi.org/10.1038/nrmicro2384

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