Immunization enhances the natural antibody repertoire

The role of immunization in the production of antibodies directed against immunogens is widely appreciated in laboratory animals and in humans. However, the role of immunization in the development of “natural antibodies” has not been investigated. Natural antibodies are those antibodies present without known history of infection or immunization, and react to a wide range of targets, including “cryptic” self-antigens that are exposed upon cell death. In this study, the ability of immunization to elicit the production of natural antibodies in laboratory rats was evaluated. Laboratory rats were immunized with a series of injections using peanut extracts (a common allergen), a high molecular weight protein conjugated to hapten (FITC-KLH), and a carbohydrate conjugated to hapten (DNPFicall). Significantly greater binding of antibodies from immunized animals compared to controls was observed to numerous autologous organ extracts (brain, kidney, liver, lung, prostate, and spleen) for both IgM and IgG, although the effect was more pronounced for IgM. These studies suggest that immunization may have at least one unforeseen benefit, enhancing networks of natural antibodies that may be important in such processes as wound repair and tumor surveillance. Such enhancement of natural antibody function may be particularly important in Western society, where decreased exposure to the environment may be associated with a weakened natural antibody repertoire

Increased Biodiversity in the Environment Improves the Humoral Response of Rats

Previous studies have compared the immune systems of wild and of laboratory rodents in an effort to determine how laboratory rodents differ from their naturally occurring relatives. This comparison serves as an indicator of what sorts of changes might exist between modern humans living in Western culture compared to our hunter-gatherer ancestors. However, immunological experiments on wild-caught animals are difficult and potentially confounded by increased levels of stress in the captive animals. In this study, the humoral immune responses of laboratory rats in a traditional laboratory environment and in an environment with enriched biodiversity were examined following immunization with a panel of antigens. Biodiversity enrichment included colonization of the laboratory animals with helminths and co-housing the laboratory animals with wild-caught rats. Increased biodiversity did not apparently affect the IgE response to peanut antigens following immunization with those antigens. However, animals housed in the enriched biodiversity setting demonstrated an increased mean humoral response to T-independent and T-dependent antigens and increased levels of “natural” antibodies directed at a xenogeneic protein and at an autologous tissue extract that were not used as immunogens

Production and Use of Hymenolepis diminuta Cysticercoids as Anti-Inflammatory Therapeutics

Helminthic therapy has shown considerable promise as a means of alleviating some inflammatory diseases that have proven resistant to pharmaceutical intervention. However, research in the field has been limited by a lack of availability to clinician scientists of a helminth that is relatively benign, non-communicable, affordable, and effectively treats disease. Previous socio-medical studies have found that some individuals self-treating with helminths to alleviate various diseases are using the rat tapeworm (cysticercoid developmental stage of Hymenolepis diminuta; HDC). In this study, we describe the production and use of HDCs in a manner that is based on reports from individuals self-treating with helminths, individuals producing helminths for self-treatment, and physicians monitoring patients that are self-treating. The helminth may fit the criteria needed by clinical scientists for clinical trials, and the methodology is apparently feasible for any medical center to reproduce. It is hoped that future clinical trials using this organism may shed light on the potential for helminthic therapy to alleviate inflammatory diseases. Further, it is hoped that studies with HDCs may provide a stepping stone toward population-wide restoration of the biota of the human body, potentially reversing the inflammatory consequences of biota depletion that currently affect Western society

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism

The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth

Lymphocyte phenotypes in wild-caught rats suggest potential mechanisms underlying increased immune sensitivity in post-industrial environments

The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to laboratory rats. On the other hand, differences in expression of markers involved in complement regulation, adhesion, signaling and maturation suggest increased complement regulation and decreased sensitivity in wild-caught rats compared to laboratory rats, and point toward complex differences between the maturation of T cells. The results potentially lend insight into the pathogenesis of post-industrial epidemics of allergy and autoimmune disease

Cromolyn ameliorates acute and chronic injury in a rat lung transplant model

BackgroundMast cells have been associated with obliterative bronchiolitis (OB) in human pulmonary allografts, although their role in the development of OB remains unknown.MethodsIn this study, we evaluated the role of mast cells in pulmonary allograft rejection using an orthotopic rat pulmonary allograft model that utilizes chronic aspiration of gastric fluid to reliably obtain OB. Pulmonary allograft recipients (n = 35) received chronic aspiration of gastric fluid with (n = 10) and without (n = 16) treatment with a mast cell membrane stabilizer, cromolyn sodium, or chronic aspiration with normal saline (n = 9) as a control.ResultsThe acute graft injury associated with long ischemic time in the model (6 hours total ischemic time; typical acute graft injury rate ~30%) was apparently blocked by cromolyn, because peri-operative mortality associated with the acute graft injury was not observed in any of the animals receiving cromolyn (p = 0.045). Further, the rats receiving cromolyn developed significantly fewer OB lesions than those treated with gastric fluid alone (p < 0.001), with a mean reduction of 46% of the airways affected.ConclusionsThese findings provide impetus for further studies aimed at elucidating the effects of cromolyn and the role of mast cells in pulmonary allotransplantation