Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis

Further to define the epitopes of PDC-E2, the major autoantigen in primary biliary cirrhosis (PBC), we have developed and characterized five human monoclonal antibodies. These antibodies were derived by fusing a regional hepatic lymph node from a patient with PBC with the mouse human heterohybrid cell line F3B6. Previous studies of epitope mapping of PDC-E2 have relied on whole sera and have suggested that the immunodominant epitope lies within the inner lipoyl domain of the molecule. However, selective absorption studies using whole sera and a series of overlapping recombinant peptides of PDC-E2 have suggested that the epitope may also include a large conformational component. Moreover, several laboratories have suggested that autoantibodies against the 2-oxo acids dehydrogenase autoantigens are cross-reactive. The five monoclonal antibodies generated included three IgG2a and two IgM antibodies and were studied for antigen specificity using recombinant PDC-E2, recombinant BCKD-E2, histone, dsDNA, IgG (Fc), collagen and a recombinant irrelevant liver specific control, the F alloantigen. The antibodies were also used to probe blots of human, bovine, mouse and rat mitochondria. Finally, fine specificity was studied by selective ELISA and absorption against overlapping expressing fragments of PDC-E2. All five monoclonals, but none of the other mitochondrial autoantigens were specific for PDC-E2. In fact, although affinity purified antibodies to PDC-E2 from patients with PBC cross-reacted with protein X, the human monoclonals did not, suggesting that protein X contains an epitope distinct from that found on PDC-E2. Additionally, all three IgG2 monoclonals recognized distinct epitopes within the inner lipoyl domain of PDC-E2. © 1992

Blowing on Embers: Commensal Microbiota and Our Immune System

Vertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal–immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens

Inability to prepare lecithin-stabilized oil-in-water emulsions by repeated membrane emulsification

Inability to prepare lecithin-stabilized oil-in-water emulsions by repeated membrane emulsificatio

"Masculinity and Maturity Taught by Mothers:" Familial Politics and Gender Identity Crisis in Western Literature and Film

Young male characters represent (whether through words or actions) cultural ideals about masculinity within literature and film. However, because masculinity is a culturally constructed identity, (there is a strong difference between “biological sex” and “social gender”), masculine identity must be learned or absorbed by the individual male character during the course of his development. While society and culture play a crucial role in the self-development and self-identification of masculinity, familial relationships are amongst the most influential aspects that shape the development of gender. This thesis focuses specifically on the development of son characters that are forced to develop their masculinity under the tutelage of mother characters due to the lack of a father figure. It also focuses on how mother characters are presented as an obstruction to the development of masculinity within their sons. Western Culture perpetuates an ideology that sons must break away from their mothers in order to achieve maturity and masculinity. Such action on the part of son characters is not easy; son characters are reliant upon their mothers as they are simultaneously nurturers and the means by which sons learn their masculinity in the absence of the father. However, son characters lacking an actual biological male as a father figure are inherently presented as immature and underdeveloped. This portrayal favors the perspective that the development of maturity within son characters requires the presence of a father figure; thus does Western Culture undermine the importance of mothers in the development of sons. This thesis is divided into four separate chapters the cover a variety of mediums and time periods. Chapter One focuses on the Homeric Epics, Chapter Two centers around William Shakespeare‟s Macbeth, Chapter Three explores Alfred Hitchcock‟s Psycho, and Chapter Four critically analyzes the modern popular culture film Fight Club, directed by David Fincher

On the preparation of lecithin-stabilized oil-in-water emulsions by multi-stage premix membrane emulsification

We report on the preparation and characterization of lecithin-stabilizedoil-in-wateremulsions (10 or 20 wt% corn oil, 2 wt% lecithin, pH 3, 100 or 150 kPa) by multi-stagepremixmembraneemulsification using a Shirasu porous glassmembrane (mean pore size 8 μm). Structural characteristics of the emulsions such as droplet size distribution, mean droplet diameter, and morphology were measured by using a laser light scattering and optical microscopy, respectively. As the number of passes through the membrane increased from 1 to 5, the transmembrane flux decreased from 30 to 1 m3 m−2 h−1. It demonstrates that lecithin emulsifier, even if its net charge is negative (pKa ∼ pH 1.5), tends to foul SPG membrane by blocking the membrane pores, which was attributed to the possible interaction between positive groups on the lecithin molecules with anionic silanol groups on the membrane surface

Functional and Homeostatic impact of Age-Related Changes in Lymph node Stroma

Adults over 65 years of age are more vulnerable to infectious disease and show poor responses to vaccination relative to those under 50. A complex set of age-related changes in the immune system is believed to be largely responsible for these defects. These changes, collectively termed immune senescence, encompass alterations in both the innate and adaptive immune systems, in the microenvironments where immune cells develop or reside, and in soluble factors that guide immune homeostasis and function. While age-related changes in primary lymphoid organs (bone marrow, and, in particular, the thymus, which involutes in the first third of life) have been long appreciated, changes affecting aging secondary lymphoid organs, and, in particular, aging lymph nodes (LNs) have been less well characterized. Over the last 20 years, LN stromal cells have emerged as key players in maintaining LN morphology and immune homeostasis, as well as in coordinating immune responses to pathogens. Here, we review recent progress in understanding the contributions of LN stromal cells to immune senescence. We discuss approaches to understand the mechanisms behind the decline in LN stromal cells and conclude by considering potential strategies to rejuvenate aging LN stroma to improve immune homeostasis, immune responses, and vaccine efficacy in the elderly.113Ysciescopu

A Fourier transform spectrometer for the measurement of atmospheric thermal radiation

Fourier transform spectrometer for measurement of atmospheric thermal radiatio