Background: Pityriasis rosea Gibert (PRG) has features similar to those of common infectious childhood diseases, suggesting a viral cause, but no agent has been identified to date. We describe 4 children with PRG and 2 with recurrent varicella who were studied using photochronography, virology and immunology. Methods: The 6 patients with skin rashes visited our pediatric clinic from April 2012 to May 2016. Photographs of their skin lesions were taken; blood, skin lesions, and/or nasal lavage samples were collected to detect varicella-zoster virus (VZV) DNA and antibodies; and skin tests were carried out to measure cell-mediated immunity to VZV. Results: Herald patches were confirmed in 2 of 4 PRG patients. No specimen cultures were positive for infectious VZV. However, VZV-DNA was detected in skin lesions of 3 PRG patients. During the acute phase, 5 patients had IgG antibodies to VZV, and skin-test reactions were positive in 5 patients. Conclusions: IgG antibody titers to VZV at rash onset were high, suggesting that they were already rising at the appearance of the rash and that reinfection with VZV must have occurred during the prodromal stage or several weeks before rash appearance in PRG patients whose immunity had declined below the threshold. Our study suggests a new pathogenesis of PRG that might help to address incongruities of past theories on PRG sites of viral entry and replication, incubation period and variations in the clinical course of PRG from prodrome to healing.

On the 25th of July, disheartening news of the untimely demise of our distinguished colleague and dear friend, John Bienenstock, reached the immunological community and was profoundly felt by mucosal immunologists. Undoubtedly, Dr. Bienenstock is one of the universally acknowledged founders of the discipline of mucosal immunology, together with several current colleagues and the recently deceased Drs. Per Brandtzaeg and Lars Ǻ Hanson. Recognition of the mucosal immune system as an integral, and perhaps the dominant component, of the entire immune system is based on quantitative studies of B and T cells as well as antibody-producing cells in mucosal lymphoid tissues. In the mid 1960's, John Bienenstock, burst into the immunological scene as a mucosal immunologist with a series of groundbreaking studies that convincingly demonstrated the integral interactions of individual components of the mucosal immune system and defined the latter's inductive and effector sites. This culminated a decade later (1974) in a foundational study of mucosal immunity in which Dr. Bienenstock showed that cells in bronchial lymphoid aggregations (BALT) could function in a similar manner to cells in Peyer's patch lymphoid aggregations (GALT) in their ability to repopulate other parts of the mucosal immune system. Thus, for the first time Bienenstock (and ultimately the rest of the immunologic community) could envision a Common Mucosal Immune System (so-named by Bienenstock) that was both a unique and vital part of the immune system as a whole. Even today, almost half a century later, this work is remembered (and cited) in our attempt to understand the immunopathology of the SARS-CoV-2 infection, an infection that initially invades the upper respiratory tract and lung tissue but can spread via routes defined by the migration of cells in the mucosal immune system. However, John Bienenstock's contributions to mucosal immunology didn't stop there. In the ensuing years he and the groups of investigators he led continued to provide impressive studies establishing the structure and production of polymeric secretory IgA, the definition of inductive and effector mucosal sites and their associated histological features, the presence of distinct phenotypes of cells in mucosal compartments, and the induction of immune responses ensuing after a variety of immunization routes. In addition, in recent years the broad yet deep knowledge of mucosal immunity this work encompasses allowed him to pursue difficult questions concerning the neurological regulation of the mucosal immune system and the impact of mucosal microbiota on the mucosal system. Overall, the continued excellence of the research embodied in these studies led to his well-deserved designation as one of the most brilliant and impactful scientists in the field of mucosal immunology. Those of us who were privileged to know John as a close, personal friend will remember his unforgettable charm as well as his witty, entertaining and generous cast of mind. At numerous meetings, he displayed not only an impressive knowledge of immunology but also a deep understanding of a broad spectrum of scientific and cultural conundrums. John's astute intellect generated a continuous stream of insightful questions and solutions as well. For this reason among others, he was an indispensable member of the early and relatively small group of mucosal immunologists establishing the field of study. John's conception of scientific life extended beyond the actual performance of science. This took the form of his prominent role in the organization of many national and international conferences, including those in Canada, the United States, and many European countries. Some of these meetings were sponsored by the Mucosal Immunity Society, and John was in fact an early organizer of the Society and its second President. In addition, he was the co-editor of the “Proceeding of International Meetings of Mucosal Immunologists” published in the Advances of Experimental Medicine and Biology, and more importantly, the co-editor of first two editions of Mucosal Immunology book published by Academic Press/Elsevier. All the while he was the sponsor and advisor to countless graduate students, post-doctoral fellows, and national and international visitors who worked in his laboratory. John was born in Hungary but his family immigrated to England in the late 1930's and John received his college and medical education in that country. After initial scientific training as a post-doctoral Fellow at Harvard, he began his lifelong career as a mucosal immunologist by working at the University of Buffalo under the guidance of Thomas Tomasi, the “father” of mucosal immunology. Then, having already established himself as a leader in mucosal immunology, he moved to MacMaster University where planted his feet and stayed on as one of the intellectual and administrative leaders of this major Canadian educational institution. Among the positions he held at MacMaster was Distinguished University Professor of Pathology and Molecular Medicine, Chair of Pathology and Vice president and Dean of the Faculty of Health Sciences. In addition, in a related position he has recently served as Director of the Brain and Body Institute at St. Joseph's Health Care in Hamilton, Canada. John's productive career and excellence was recognized by many awards including an Honorary Degree of Doctor of Medicine, Goteborg University, Sweden, the MacMaster Community Distinction Award, election to the Canadian Medical Hall of Fame, the Order of Canada from the Canadian government, the designation as a Distinguished University Professor at MacMaster University, and the designation as Distinction as the Fellow of the Royal Society of Canada. John is survived by his wife for over 60 years, Dr. Audrey (Dody) Sanders, herself a remarkable scholar and physician who served as the president of the Royal College of Physicians and Surgeons of Canada. In addition to his exceptional scholarly achievements, we will remember John as a kind, caring, and generous friend who brought pleasure and inspiration to all of us. We shall miss him greatly. The authors declare no competing interests.

The information summarized in the various comprehensive presentations in this workshop represented a diverse spectrum of historical, evolutionary, and functional aspects of mammalian lactation and the process of breastfeeding. This workshop was dedicated to Prof. Lars A. Hanson (MD, PhD) for his outstanding contributions to the understanding of the biology of milk and the dissemination of knowledge on breastfeeding to advance current practices of breastfeeding in the contemporary human society worldwide. The dedication ceremony was followed by scientific presentations in session I of the workshop with the keynote addressed by Olav T. Oftedal. Oftedal provided an elegant perspective of the evolution of lactation in different mammalian species. Based on studies on synapsids (ancestral to mammals, which appear to have diverged from sauropsids [ancestral to crocodiles, lizards, and birds]), he proposed that lactation may have first evolved as a source of moisture and antimicrobial compounds for parchment-shelled eggs, followed by the evolution of some skin secretions, which eventually became milk. It was suggested that among basal animals (monotremes), each mammary gland develops as a triad in association with a hair follicle and sebaceous gland as a mammopilo-sebaceous unit (MPSU). In other mammalian species, such as marsupials, there is a similar triad, but the hair follicles are shed during development. In the diverse group of eutherian mammals, some show no association with the mammary hair, while others, such as the horse, develop as MPSU with mammary hair and sebaceous glands present in the mammary gland. Ogra PL, Walker WA, Lönnerdal B (eds): Milk, Mucosal Immunity and the Microbiome: Impact on the Neonate. Nestlé Nutr Inst Workshop Ser. Basel, Karger, 2020, vol 94, pp 59–64 (DOI:10.1159/000505425)

The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV-2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory mucosal surfaces, during both inductive and effector phases of the response. However, almost all studies of the immune response in COVID-19 have focused exclusively on serum antibodies and systemic cell-mediated immunity including innate responses. This article proposes that there is a significant role for mucosal immunity and for secretory as well as circulating IgA antibodies in COVID-19, and that it is important to elucidate this in order to comprehend especially the asymptomatic and mild states of the infection, which appear to account for the majority of cases. Moreover, it is possible that mucosal immunity can be exploited for beneficial diagnostic, therapeutic, or prophylactic purposes.

The mucosal surfaces and the skin are the primary sites of interactions between the mammalian host and the external environment. These sites are exposed continuously to the diverse components of the environment, including subcellular, unicellular and multicellular organisms, dietary agents and food products; and numerous other soluble or cellular air or water borne products. The development of innate and adaptive immunity in the mucosal surfaces and the skin are the principal mechanism of mammalian defense evolved to date, in order to maintain effective homeostatic balance between the host and the external environment. The innate immune functions are mediated by a number of host specific Pathogen Recognition Receptors (PRR), designed to recognize unique Pathogen Associated Molecular Patterns (PAMP), essential to the molecular structure of the microorganism. The major components of specific adaptive immunity in the mucosal surfaces include the organized antigen-reactive lymphoid follicles in different inductive mucosal sites and the effector sites of the lamina propria and sub-epithelial regions, which contain lymphoid and plasma cells, derived by the homing of antigen sensitized cells from the inductive sites. The acquisition of environmental microbiome by the neonate in its mucosal surfaces and the skin, which begins before or immediately after birth, has been shown to play a critical and complex role in the development of mucosal immunity. This report provides an overview of the mammalian microbiome and highlights its role in the evolution and functional development of immunologic defenses in the mucosal surface under normal physiologic conditions and during infectious and non-infectious inflammatory pathologic states associated with altered microbiota.

Objective The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Conclusion Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. Implications for Practice The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.

ObjectiveThe objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media.Data SourcesPubMed database of the National Library of Medicine.Review MethodsThree subpanels with co‐chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel.ConclusionExcellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory‐based basic studies, cell‐based assays, work in animal models, and clinical studies.Implications for PracticeThe advances of the past 4 years formed the basis of a series of short‐term and long‐term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.

Objective. The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Conclusion. Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratorybased basic studies, cell-based assays, work in animal models, and clinical studies. Implications for Practice. The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.

Objective. The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Conclusion. Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. Implications for Practice. The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.

Paired samples ofmilk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1(3, IL-6, IL-12, tumor necrosis factor a (FNF-a), and interferon- "1 (IFN-'y) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by re- verse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five sam- pies of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1�3, IL-6, and TNF-a. No IL-12 or IFN-y activity was de- tected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-a activity in about 10% of the serum samples tested. However, no IL-1�3, IL-12, or IFN-y activity was demonstrated in any of the se- rum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1�3, TNF-a, and IL-6, and IFN-y mRNA in six ofeight subjects, although no IFN- '1 was detected in any ofthe 20 samples ofmilk tested. RSV exposure resulted in a 2- to 100-fold increase in the expression of IL-ifS, IL-6, and TNF-a mRNA as well as cytokine protein. Although RSV infection enhanced the expression of IFN-y mRNA, no detect- able IFN-'y was produced by the milk macrophages. These observations suggest that the milk macrophages are actively engaged in the physiological production of IL-1�, IL-6, TNF-a, and WN-y in the mammary gland and continue to possess the capacity to increase production ofthese cytokines in response to RSV and possibly other viral infections. J. Leukoc. Biol. 61: 630-636; 1997.

The proceedings of the symposium, sponsored primarily by the National Institute of Child Health and Human Development, critically evaluate the current state of knowledge concerning the protective role of immune agents found in milk, provide up-to-date information on milk factors with respect to thei

Since the resolution of the World Assembly in 1988 to eradicate polio globally, substantial progress toward this target has been achieved, but the final goal remains elusive. India and other tropical developing countries present a unique challenge because of the much lower oral poliovirus vaccine (OPV) immunogenicity compared to industrialized countries, both in terms of humoral and mucosal immunity. To overcome this challenge, further research is needed to elucidate the causes for the suboptimal OPV immunogenicity, better defining the optimal vaccine schedules and delivery strategies, developing and evaluating adjuvants to boost OPV immunogenicity, and improving the methods for directly measuring mucosal immunity.

The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

The development, structural diversification, and functional maturation of mammalian immunologic repertoire at mucosal surfaces and the systemic lymphoid tissue is a remarkably dynamic and continuous process, which begins in early fetal life and eventually culminates in variable degree of senescence or cellular death with advancing age. This brief overview will highlight the status of our current understanding of the ontogeny of mucosal immunologic response. The role of mucosal microflora and other environmental macromolecules in the regulation of mucosal immunity relative to the process of ageing will also be reviewed.

The major mechanisms of mucosal defense in the neonate consist of a variety of nonspecific barriers, and innate and specific adaptive immune responses. The functions of innate immunity in the mucosal surfaces are mediated by host-specific microbial–pathogen recognition receptors, designed to recognize unique microbial-associated molecular patterns integral to the structure of most microorganisms. Other mechanisms include many antimicrobial peptides, macrophages, dendritic cells, complement components and host-derived cellular and soluble products. The important elements of neonatal mucosal adaptive immunity include the inductive sites, such as the Peyer's patches and other lymphoid structures in the respiratory and gastrointestinal tracts, the nasopharyngeal and sublingual tissues, the subepithelial and intraepithelial sites in most external mucosal surfaces, including the genital tract and the mammary glands. These sites contain lymphoid cells derived by the homing of antigen-activated cells from the inductive sites. Activated B cells, mostly IgA (up to 80%) are detected in the mucosal tissues shortly after birth. However, IgA-producing plasma cells are generally detected in the mucosa approximately 7–10 days of age. With progressive environmental antigenic stimulation, the number of circulating IgA cells increase significantly by 1 month of age. The postnatal development of mucosal immunity is critically influenced by the acquisition and nature of mucosal microflora, and the temporal nature and qualitative and quantitative aspects of dietary antigens and other environmental agents introduced in the neonatal period. Mucosal immune responses are generally protective against disease-producing organisms and environmental macromolecules. The mucosal immune responses may also be pathologic and foster the induction of immunologically mediated disease states and autoimmunity. The development of secretory IgA and other antimicrobial mucosal responses as well as the induction of tolerance in the neonatal period and early infancy are essential for the maintenance of mucosal homeostasis in early childhood and prevention of disease later in life.

The primary focus of the entire immune system on protecting the mucosal surfaces – consisting mainly of the oro-gastrointestinal, respiratory, and genital tracts – is now beyond dispute and widely recognized. The evidence is clearly seen in the distribution of lymphoid cells throughout the body, the majority of these cells being found in the intestinal tract and other mucosal surfaces which are exposed to the external environment and subject to colonization by a huge variety of microorganisms (Pabst et al., 2008). In addition, IgA is by far the most abundantly produced immunoglobulin (Ig) isotype in the human body, accounting for approximately two-thirds of all Ig production. Altogether, synthesis of IgA amounts to some 5-10 g/day, of which the majority is secretory IgA (S-IgA; Russell, 2007). Thus the immune system deploys its resources according to where the threats to health mainly arise, and most infections directly afflict or invade through the oral cavity, and the gastrointestinal, respiratory, and genital tracts. However, the mucosal immune system faces a dilemma, because most of the foreign antigenic material present especially in the gastrointestinal tract consists of food as well as a huge number of microorganisms comprising the commensal microbiota amounting to an estimated 1014 cells of probably thousands of different species. Thus, it must distinguish not only between self and non-self, but also between the mass of harmless food antigens, commensals many of which are beneficial, and potentially dangerous pathogens. Considerable strides have been made in recent years in comprehending the mechanisms responsible for responsiveness or conversely non-responsiveness