Allergy, Asthma and Immunology

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Front. Immunol., 06 August 2013 | doi: 10.3389/fimmu.2013.00222

Secretory IgA: designed for anti-microbial defense

Per Brandtzaeg^1,2*

¹Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Centre for Immune Regulation (CIR), University of Oslo, Oslo, Norway
²Department of Pathology, Oslo University Hospital Rikshospitalet, Oslo, Norway

Prevention of infections by vaccination remains a compelling goal to improve public health. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion – a term coined for non-inflammatory antibody shielding of internal body surfaces, mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA), produced by local plasma cells (PCs) stimulated by antigens that target the mucose. SIgA was early shown to be complexed with an epithelial glycoprotein – the secretory component (SC). A common SC-dependent transport mechanism for pIgA and pentameric IgM was then proposed, implying that membrane SC acts as a receptor, now usually called the polymeric Ig receptor (pIgR). From the basolateral surface, pIg-pIgR complexes are taken up by endocytosis and then extruded into the lumen after apical cleavage of the receptor – bound SC having stabilizing and innate functions in the secretory antibodies. Mice deficient for pIgR show that this is the only receptor responsible for epithelial export of IgA and IgM. These knockout mice show a variety of defects in their mucosal defense and changes in their intestinal microbiota. In the gut, induction of B-cells occurs in gut-associated lymphoid tissue, particularly the Peyer’s patches and isolated lymphoid follicles, but also in mesenteric lymph nodes. PC differentiation is accomplished in the lamina propria to which the activated memory/effector B-cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue but by different homing receptors. This compartmentalization is a challenge for mucosal vaccination, as are the mechanisms used by the mucosal immune system to discriminate between commensal symbionts (mutualism), pathobionts, and overt pathogens (elimination).

Keywords: mucosa, antibodies, commensals, pathogens, MALT, GALT, NALT, germinal centers

Citation: Brandtzaeg P (2013) Secretory IgA: designed for anti-microbial defense. Front. Immunol. 4:222. doi: 10.3389/fimmu.2013.00222

Received: 06 June 2013; Paper pending published: 30 June 2013;
Accepted: 16 July 2013; Published online: 06 August 2013.

Edited by:

Rajaraman D. Eri, University of Tasmania, Australia

Reviewed by:

Diane Bimczok, University of Alabama at Birmingham, USA
Rita Carsetti, Ospedale Pediatrico Bambino Gesù, Italy

Copyright: © 2013 Brandtzaeg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Per Brandtzaeg, Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Oslo University Hospital Rikshospitalet, P.O. Box 4950, N-0424 Oslo, Norway e-mail: per.brandtzaeg@medisin.uio.no

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Quantification of total T-cell receptor diversity by flow cytometry and spectratyping

Methodology article

Quantification of total T-cell receptor diversity by flow cytometry and spectratyping

Stanca M Ciupe, Blythe H Devlin, Mary Louise Markert and Thomas B Kepler

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BMC Immunology 2013, 14:35 doi:10.1186/1471-2172-14-35

Published: 6 August 2013

Abstract (provisional)

Background

T-cell receptor diversity correlates with immune competency and is of particular interest in patients undergoing immune reconstitution. Spectratyping generates data about T-cell receptor CDR3 length distribution for each BV gene but is technically complex. Flow cytometry can also be used to generate data about T-cell receptor BV gene usage, but its utility has not been compared to or tested in combination with spectratyping.

Results

Using flow cytometry and spectratype data, we have defined a divergence metric that quantifies the deviation from normal of T-cell receptor repertoire. We have shown that the sample size is a sensitive parameter in the predicted flow divergence values, but not in the spectratype divergence values. We have derived two ways to correct for the measurement bias using mathematical and statistical approaches and have predicted a lower bound in the number of lymphocytes needed when using the divergence as a substitute for diversity.

Conclusions

Using both flow cytometry and spectratyping of T-cells, we have defined the divergence measure as an indirect measure of T-cell receptor diversity. We have shown the dependence of the divergence measure on the sample size before it can be used to make predictions regarding the diversity of the T-cell receptor repertoire.

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The impact of aging on regulatory T-cells

MINI REVIEW ARTICLE

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Front. Immunol., 06 August 2013 | doi: 10.3389/fimmu.2013.00231

The impact of aging on regulatory T-cells

Johannes Fessler¹, Anja Ficjan¹, Christina Duftner² andChristian Dejaco¹*

¹Department of Rheumatology and Immunology, Medical University Graz, Graz, Austria
²Department of Internal Medicine, General Hospital Kufstein, Kufstein, Austria

Age-related deviations of the immune system contribute to a higher likelihood of infections, cancer, and autoimmunity in the elderly. Senescence of T-lymphocytes is characterized by phenotypical and functional changes including the loss of characteristic T-cell surface markers, while an increase of stimulatory receptors, cytotoxicity as well as resistance against apoptosis is observed. One of the key mediators of immune regulation are naturally occurring regulatory T-cells (T_regs). T_regsexpress high levels of CD25 and the intracellular protein forkhead box P3; they exert their suppressive functions in contact-dependent as well as contact-independent manners. Quantitative and qualitative defects of T_regswere observed in patients with autoimmune diseases. Increased T_regactivity was shown to suppress anti-tumor and anti-infection immunity. The effect of aging on T_regs, and the possible contribution of age-related changes of the T_reg pool to the pathophysiology of diseases in the elderly are still poorly understood. T_reg homeostasis depends on an intact thymic function and current data suggest that conversion of non-regulatory T-cells into T_regs as well as peripheral expansion of existing T_regscompensates for thymic involution after puberty to maintain constant T_regnumbers. In the conventional T-cell subset, peripheral proliferation of T-cells is associated with replicative senescence leading to phenotypical and functional changes. For T_regs, different developmental stages were also described; however, replicative senescence of T_regs has not been observed yet.

Keywords: FOXP3, regulatory T-lymphocyte, aging, cellular senescence, thymus, suppressor cells

Citation: Fessler J, Ficjan A, Duftner C and Dejaco C (2013) The impact of aging on regulatory T-cells. Front. Immunol. 4:231. doi: 10.3389/fimmu.2013.00231

Received: 28 March 2013; Accepted: 22 July 2013;
Published online: 06 August 2013.

Edited by:

Dietmar Herndler-Brandstetter, Yale University School of Medicine, USA

Reviewed by:

Nikolai Petrovsky, Flinders Medical Centre, Australia
Tyler Curiel, University of Texas Health Science Center at San Antonio, USA

Copyright: © 2013 Fessler, Ficjan, Duftner and Dejaco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Christian Dejaco, Department of Rheumatology and Immunology, Medical University Graz, Auenbruggerplatz 15, A-8036 Graz, Austria e-mail: christian.dejaco@gmx.net

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