Beneficial autoimmunity at body surfaces – immune surveillance and rapid type 2 immunity regulate tissue homeostasis and cancer

Epithelial cells line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation or toxins cause activation of epithelial cells with release of cytokines and chemokines as well as alterations in the expression of cell surface ligands. Such display of epithelial stress is rapidly sensed by tissue resident immunocytes, which can directly interact with self-moieties on epithelial cells and initiate both local and systemic immune responses. Epithelial cells are thus key drivers of immune surveillance at body surface tissues. However, epithelial cells have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis

Differences and Commonalities in Physical, Chemical and Mineralogical Properties of Zanzibari Geophagic Soils

The function of human geophagy has long been questioned. We sought to test hypotheses concerning its potential physiological effects through analysis of soils and patterns in geophagy behavior. Eleven samples of geophagic soils consumed by pregnant women on Pemba Island, Zanzibar, Tanzania, were characterized according to their color, texture, major element chemistry, trace element chemistry, bulk mineralogy, and clay mineralogy. An epidemiological study (N = 2367) and ethnographic interviews (N = 57) on Pemba yielded information about geophagic behaviors and socio-demographic and biological characteristics of those who consumed earth. The soils varied widely in color, ranging from light red to white through various shades of brown and yellow, and texture ranged from clay to sand. Major element chemistry of the soils also varied greatly; most were low in Fe and Ca. Trace elements, whether of biological or non-biological significance, were uniformly low when compared with normal ranges of mineral soils. The sole commonality among the samples is that all clay fractions were dominated by a kaolin mineral: kaolinite, halloysite, or a mixture of both. Geophagy behavior also varied greatly, with one major exception: a greater proportion of pregnant women (7.1%) and young children (4.5%) consumed earth than non-pregnant women (0.2%) or men (0%). The presence of kaolin mineral in all samples, its palliative and detoxifying properties, and the highest prevalence of geophagy among those most biologically vulnerable suggest that geophagy may be a protective behavior

Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development

Toward a Comprehensive Approach to the Collection and Analysis of Pica Substances, with Emphasis on Geophagic Materials

Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem.In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica.Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma-atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles.This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption

Human Organisms from an Evolutionary Perspective: Its Significance for Medicine

Defenders of evolutionary medicine claim that medical professionals and public health officials would do well to consider the role of evolutionary biology with respect to the teaching, research, and judgments pertaining to medical theory and practice. An integral part of their argument is that the human body should be understood as a bundle of evolutionary compromises. Such an appreciation, which includes a proper understanding of biological function and physiological homeostasis, would provide a crucial perspective regarding the understanding and securing of human health needs currently lacking in the medical arena

Social constructionism as cognitive science

Social constructionism is a broad position that emphasizes the importance of human social processes in psychology. These processes are generally associated with language and the ability to construct stories that conform to the emergent rules of 'language games'. This view allows one to espouse a variety of critical postures with regard to realist commitments within the social and behavioural sciences, ranging from outright relativism (language constructs all of our concepts) to a more moderate respect for the 'barrier' that linguistic descriptions can place between us and reality. This paper first outlines some possible social constructionist viewpoints and then goes on to show how each of them conforms to the basic principles of information theory. After establishing this relation the paper then argues that this leads to a deal of commonality between social constructionist positions and the baseline aims of cognitive science. Finally, the paper argues that if information theory is held in common this both suggests future research collaborations and helps to 'mop up' some of the arguments surrounding realist commitments