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Article ; Online: Pillars Article: Mucosal and Glandular Distribution of Immunoglobulin Components: Differential Localization of Free and Bound SC in Secretory Epithelial Cells.

Brandtzaeg, Per

Journal of immunology (Baltimore, Md. : 1950)

2017 Volume 198, Issue 5, Page(s) 1768–1774

Language	English
Publishing date	2017-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
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Article ; Online: Neisseria meningitidis

Brusletto, Berit Sletbakk / Hellerud, Bernt Christian / Øvstebø, Reidun / Brandtzaeg, Petter

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1298360

Abstract: Background: Neisseria meningitidis: Objective: 1) To explore the feasibility of measuring LPS levels in tissues from the large organs in patients with meningococcal septic shock and in a porcine meningococcal septic shock model. 2) To evaluate the ... ...

Abstract	Background: Neisseria meningitidis Objective: 1) To explore the feasibility of measuring LPS levels in tissues from the large organs in patients with meningococcal septic shock and in a porcine meningococcal septic shock model. 2) To evaluate the extent of contamination of non-specific LPS during the preparation of tissue samples. Patients and methods: Plasma, serum, and fresh frozen (FF) tissue samples from the large organs of three patients with lethal meningococcal septic shock and two patients with lethal pneumococcal disease. Samples from a porcine meningococcal septic shock model were included. Frozen tissue samples were thawed, homogenized, and prepared for quantification of LPS by Pyrochrome Results: N. meningitidis Conclusion: Our results suggest that LPS can be quantified in mammalian tissues by using the LAL assay.
MeSH term(s)	Animals ; Humans ; DNA ; Lipopolysaccharides ; Mammals ; Meningitis, Meningococcal ; Meningococcal Infections ; Neisseria meningitidis ; Pneumococcal Infections ; Sepsis ; Shock, Septic ; Swine
Chemical Substances	DNA (9007-49-2) ; Lipopolysaccharides
Language	English
Publishing date	2023-11-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1298360
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Article ; Online: Gate-keeper function of the intestinal epithelium.

Brandtzaeg, P

Beneficial microbes

2013 Volume 4, Issue 1, Page(s) 67–82

Abstract: There is currently a major focus on the role of the gut barrier function in balancing mucosal immune responses. Increased epithelial permeability for exogenous antigens is a crucial primary or secondary event in the pathogenesis of several disorders ... ...

Abstract	There is currently a major focus on the role of the gut barrier function in balancing mucosal immune responses. Increased epithelial permeability for exogenous antigens is a crucial primary or secondary event in the pathogenesis of several disorders affecting body surfaces and beyond. The epithelial gate-keeper function is determined by the individual's age (e.g. preterm vs. term infant), diet, genetics, mucus composition, interactions between mast cells, nerves and neuropeptides, concurrent infection, the commensal microbiota and the epithelium-shielding effect of secretory IgA (SIgA) antibodies provided by breast milk or produced in the individual's gut. The integrity of the epithelial barrier furthermore depends on homeostatic regulatory mechanisms, including mucosal induction of regulatory T cells, where commensal microbiota-host interactions apparently play decisive roles. Thus, both extrinsic and intrinsic factors have been identified that may have an impact on the dynamics of the epithelial cell-cell junctions in the gut and thereby increase or reduce paracellular permeability. Experiments have shown that SIgA normally cooperates with innate defence factors to protect the epithelium and reinforce its barrier function. In the absence of SIgA commensal gut bacteria overstimulate innate epithelial immunity at the expense of expression of genes that regulate fat and carbohydrate metabolism, resulting in an epithelial gene signature that correlates with the development of lipid malabsorption. This shows that the intestinal epithelial barrier is a cross-road between defence and nutrition, and that SIgA is essential to keep the balance between these two functions.
MeSH term(s)	Humans ; Immunity, Mucosal ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/physiology ; Nutritional Physiological Phenomena
Language	English
Publishing date	2013-03-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2561259-1
ISSN	1876-2891 ; 1876-2883
ISSN (online)	1876-2891
ISSN	1876-2883
DOI	10.3920/BM2012.0024
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Article: Secretory immunity with special reference to the oral cavity.

Brandtzaeg, Per

Journal of oral microbiology

2013 Volume 5

Abstract: The two principal antibody classes present in saliva are secretory IgA (SIgA) and IgG; the former is produced as dimeric IgA by local plasma cells (PCs) in the stroma of salivary glands and is transported through secretory epithelia by the polymeric Ig ... ...

Abstract	The two principal antibody classes present in saliva are secretory IgA (SIgA) and IgG; the former is produced as dimeric IgA by local plasma cells (PCs) in the stroma of salivary glands and is transported through secretory epithelia by the polymeric Ig receptor (pIgR), also named membrane secretory component (SC). Most IgG in saliva is derived from the blood circulation by passive leakage mainly via gingival crevicular epithelium, although some may be locally produced in the gingiva or salivary glands. Gut-associated lymphoid tissue (GALT) and nasopharynx-associated lymphoid tissue (NALT) do not contribute equally to the pool of memory/effector B cells differentiating to mucosal PCs throughout the body. Thus, enteric immunostimulation may not be the best way to activate the production of salivary IgA antibodies although the level of specific SIgA in saliva may still reflect an intestinal immune response after enteric immunization. It remains unknown whether the IgA response in submandibular/sublingual glands is better related to B-cell induction in GALT than the parotid response. Such disparity is suggested by the levels of IgA in submandibular secretions of AIDS patients, paralleling their highly upregulated intestinal IgA system, while the parotid IgA level is decreased. Parotid SIgA could more consistently be linked to immune induction in palatine tonsils/adenoids (human NALT) and cervical lymph nodes, as supported by the homing molecule profile observed after immune induction at these sites. Several other variables influence the levels of antibodies in salivary secretions. These include difficulties with reproducibility and standardization of immunoassays, the impact of flow rate, acute or chronic stress, protein loss during sample handling, and uncontrolled admixture of serum-derived IgG and monomeric IgA. Despite these problems, saliva is an easily accessible biological fluid with interesting scientific and clinical potentials.
Language	English
Publishing date	2013-03-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2523919-3
ISSN	2000-2297
ISSN	2000-2297
DOI	10.3402/jom.v5i0.20401
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Article: Secretory IgA: Designed for Anti-Microbial Defense.

Brandtzaeg, Per

Frontiers in immunology

2013 Volume 4, Page(s) 222

Abstract: 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 ...

Abstract	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).
Language	English
Publishing date	2013-08-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2013.00222
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Article: Mechanisms of gastrointestinal reactions to food.

Brandtzaeg, P

Environmental toxicology and pharmacology

2011 Volume 4, Issue 1-2, Page(s) 9–24

Abstract: Much of the genetic information that modulates mucosal immune responses was encoded several million years ago and has subsequently been subjected to modifications selected by the impact of microorganisms and food antigens. Confronted with these ... ...

Abstract	Much of the genetic information that modulates mucosal immune responses was encoded several million years ago and has subsequently been subjected to modifications selected by the impact of microorganisms and food antigens. Confronted with these challenges, the intestinal immune system has developed two arms: (1) immune exclusion performed mainly by secretory IgA antibodies to inhibit colonization of pathogenic microorganisms and penetration of harmful antigens; and (2) down-regulatory mechanisms to avoid local and peripheral overreaction (hypersensitivity) towards innocuous substances. The latter phenomenon is called oral tolerance and apparently explains why most individuals show no adverse immune reactions food. When the mucosal barrier function is insufficient, tolerance to dietary antigens is abrogated in genetically susceptible individuals. This is most likely to occur during the vulnerable period after birth before the immunoregulatory network has been established. Breast-feeding appears to be immunologically important during this period, not only to substitute for the infant's lacking secretory antibodies but also because of its immune-modulating effects.
Language	English
Publishing date	2011-07-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1318302-3
ISSN	1382-6689
ISSN	1382-6689
DOI	10.1016/s1382-6689(97)10036-9
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Article ; Online: Homeostatic impact of indigenous microbiota and secretory immunity.

Brandtzaeg, P

Beneficial microbes

2010 Volume 1, Issue 3, Page(s) 211–227

Abstract: In the process of evolution, the mucosal immune system has generated two layers of anti-inflammatory defence: (1) immune exclusion performed by secretory IgA (and secretory IgM) antibodies to modulate or inhibit surface colonisation of microorganisms and ...

Abstract	In the process of evolution, the mucosal immune system has generated two layers of anti-inflammatory defence: (1) immune exclusion performed by secretory IgA (and secretory IgM) antibodies to modulate or inhibit surface colonisation of microorganisms and dampen penetration of potentially dangerous antigens; and (2) suppressive mechanisms to avoid local and peripheral hypersensitivity to innocuous antigens, particularly food proteins and components of commensal bacteria. When induced via the gut, the latter phenomenon is called 'oral tolerance', which mainly depends on the development of regulatory T (Treg) cells in mesenteric lymph nodes to which mucosal dendritic cells (DCs) carry exogenous antigens and become conditioned for induction of Treg cells. Mucosally induced tolerance appears to be a rather robust adaptive immune function in view of the fact that large amounts of food proteins pass through the gut, while overt and persistent food allergy is not so common. DCs are 'decision makers' in the immune system when they perform their antigen-presenting function, thus linking innate and adaptive immunity by sensing the exogenous mucosal impact (e.g. conserved microbial molecular patterns). A balanced indigenous microbiota is required to drive the normal development of both mucosa-associated lymphoid tissue, the epithelial barrier with its secretory IgA (and IgM) system, and mucosally induced tolerance mechanisms including the generation of Treg cells. Notably, polymeric Ig receptor (pIgR/SC) knock-out mice that lack secretory IgA and IgM antibodies show reduced epithelial barrier function and increased uptake of antigens from food and commensal bacteria. They therefore have a hyper-reactive immune system and show predisposition for systemic anaphylaxis after sensitisation; but this development is counteracted by enhanced oral tolerance induction as a homeostatic back-up mechanism.
MeSH term(s)	Animals ; Homeostasis ; Humans ; Immunity, Mucosal ; Immunoglobulin A, Secretory/immunology ; Immunoglobulin M/immunology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/microbiology ; Metagenome ; Mice
Chemical Substances	Immunoglobulin A, Secretory ; Immunoglobulin M ; secretory IgM
Language	English
Publishing date	2010-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2561259-1
ISSN	1876-2891 ; 1876-2883
ISSN (online)	1876-2891
ISSN	1876-2883
DOI	10.3920/BM2010.0009
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Article ; Online: Potential of nasopharynx-associated lymphoid tissue for vaccine responses in the airways.

Brandtzaeg, Per

American journal of respiratory and critical care medicine

2011 Volume 183, Issue 12, Page(s) 1595–1604

Abstract: Nasopharynx-associated lymphoid tissue (NALT), constituting Waldeyer's ring in humans, is a unique inductive site for B-cell responses and plasma cell generation. This makes the nasal route of vaccine administration interesting for induction of mucosal ... ...

Abstract	Nasopharynx-associated lymphoid tissue (NALT), constituting Waldeyer's ring in humans, is a unique inductive site for B-cell responses and plasma cell generation. This makes the nasal route of vaccine administration interesting for induction of mucosal and systemic antibodies. The unpaired nasopharyngeal tonsil (adenoids) and the paired palatine tonsils are prominent NALT structures, functionally similar to the paired rodent NALT structures located dorsal to the cartilaginous soft palate. Human NALT is more strategically located, however, because its elements are exposed to both airborne and alimentary antigens and have antigen-retaining crypts. It also shows similarities with lymph nodes and participates both in systemic- and secretory-type mucosal immunity. Primary follicles occur at 16 weeks of gestation, which is similar to Peyer's patches but different from rodent NALT whose organogenesis begins at birth. The formation of germinal centers reflecting B-cell activation does not take place until shortly after birth, and terminal differentiation of plasma cell can be seen about 2 weeks postnatally. Germinal centers arise in T cell-dependent B-cell responses and are associated with somatic hypermutation of Ig V-region genes. Downstream switching to various Ig isotypes also takes place, with or without concurrent expression of the J-chain gene. The J chain is a crucial part of dimeric IgA and pentameric IgM, making these Ig polymers able to interact with the epithelial polymeric Ig receptor. This interaction is central in the formation of secretory IgA and secretory IgM. Accumulating evidence suggests a major role for NALT in antibody immunity of the respiratory tract and associated glands.
MeSH term(s)	Adenoidectomy ; B-Lymphocytes/immunology ; Germinal Center ; Humans ; Immunologic Memory/physiology ; Lymphoid Tissue/immunology ; Nasopharynx/immunology ; Palatine Tonsil/immunology ; Plasma Cells/immunology ; Respiratory Mucosa/immunology ; Tonsillectomy ; Vaccination/methods ; Vaccines/administration & dosage
Chemical Substances	Vaccines
Language	English
Publishing date	2011-06-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201011-1783OC
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Article ; Online: Immune functions of nasopharyngeal lymphoid tissue.

Brandtzaeg, Per

Advances in oto-rhino-laryngology

2011 Volume 72, Page(s) 20–24

Abstract: This brief review will focus on nasopharynx-associated lymphoid tissue as a unique inductive immune site for B cell responses and plasma cell generation. The anatomical and immunological characteristics of Waldeyer's lymphoid ring should make the nasal ... ...

Abstract	This brief review will focus on nasopharynx-associated lymphoid tissue as a unique inductive immune site for B cell responses and plasma cell generation. The anatomical and immunological characteristics of Waldeyer's lymphoid ring should make the nasal route for vaccine administration highly relevant in future clinical trials to stimulate both mucosal and systemic immunity. In this context, the potential immunological consequences of removing both the tonsils and the adenoids have to be considered.
MeSH term(s)	B-Lymphocytes/immunology ; Humans ; Immunity, Cellular ; Immunity, Mucosal/physiology ; Lymphocyte Activation ; Lymphoid Tissue/immunology ; Nasopharynx/immunology ; Palatine Tonsil/immunology ; Respiratory Mucosa/immunology ; Respiratory Tract Infections/immunology
Language	English
Publishing date	2011
Publishing country	Switzerland
Document type	Lectures
ISSN	1662-2847 ; 0065-3071
ISSN (online)	1662-2847
ISSN	0065-3071
DOI	10.1159/000324588
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Article ; Online: The gut as communicator between environment and host: immunological consequences.

Brandtzaeg, Per

European journal of pharmacology

2011 Volume 668 Suppl 1, Page(s) S16–32

Abstract: During human evolution, the mucosal immune system developed two anti-inflammatory mechanisms: immune exclusion by secretory antibodies (SIgA and SIgM) to control epithelial colonization of microorganisms and inhibit penetration of harmful substances; and ...

Abstract	During human evolution, the mucosal immune system developed two anti-inflammatory mechanisms: immune exclusion by secretory antibodies (SIgA and SIgM) to control epithelial colonization of microorganisms and inhibit penetration of harmful substances; and immunosuppression to counteract local and peripheral hypersensitivity against innocuous antigens such as food proteins. The latter function is referred to as oral tolerance when induced via the gut. Similar mechanisms also control immunity to commensal bacteria. The development of immune homeostasis depends on "windows of opportunity" where adaptive and innate immunities are coordinated by antigen-presenting cells; their function is not only influenced by microbial products but also by dietary constituents, including vitamin A and lipids like polyunsaturated omega-3 fatty acids. These factors can in several ways exert beneficial effects on the immunophenotype of the infant. Also breast milk provides immune-modulating factors and SIgA antibodies - reinforcing the gut barrier. Mucosal immunity is most abundantly expressed in the gut, and the intestinal mucosa of an adult contains at least 80% of the body's activated B cells - terminally differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric IgA which is exported by secretory epithelia expressing the polymeric Ig receptor (pIgR), also called membrane secretory component (SC). Immune exclusion is therefore performed mainly by SIgA. Notably, pIgR knockout mice which lack SIgs show increased uptake of food and microbial antigens and they have a hyper-reactive immune system with disposition for anaphylaxis; but this untoward development is counteracted by cognate oral tolerance induction as a homeostatic back-up mechanism.
MeSH term(s)	Adaptive Immunity ; Animals ; Environment ; Gastrointestinal Tract/immunology ; Gastrointestinal Tract/metabolism ; Gastrointestinal Tract/microbiology ; Gastrointestinal Tract/secretion ; Homeostasis/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Hypersensitivity/immunology ; Hypersensitivity/microbiology
Language	English
Publishing date	2011-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2011.07.006
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