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Hygiene hypothesis and allergic pathologies. “another problem with having money” Introduction- What is the Hygiene Hypothesis • Definition 1: The hygiene hypothesis, suggests an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies, asthma and recent evidence suggests also autoimmune disorders. • Definition 2:The hygiene hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms (e.g., gut flora or probiotics), and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system Introduction- What is an allergy • A common example is allergic rhinittis caused by the body reaction to harmless pollen as a forgein and dangerous subtance . • This leads to a immune response which leads to antibodies being produced against pollen. • This leads to typical symptoms of inflammation :rubor tumor calor dolor. Introduction- What is an autoimmune disorder. • A common example is multiple sclerosis caused by the body reaction to its own nerve bodies which are detected are forgein. • This leads to a immune response which leads to destruction of the bodies own nerve strutures. • Other examples frequently encountered include : SLE, Rheumatic fever, Hasimotos throiditis. IMMUNOREGULATORY SUBSETS OF T CELLS - mature T cells (TH0) differentiate into functionally distinct subsets after antigen stimulation presentation of microbial. Ag (LPS, CpG, lipoteichoic a.) presentation of environmental. Ag nonmicrobial origin TH0 (allergens) dendritic c., macrophage, B-cells, intensive, long term IL-12 TH1 TH1 TH1 cytotoxic reactivity immunopathological reaction IVth type weak, short term IL-4 INHIBITION TH2 TH2 TH2 antibodies production, isotypic switching immunopathological reaction Ist type Pathogensis • Allergic diseases are caused by harmless antigens such as Pollen in allergic rhinittis (hayfever) via Th2 • Many bacteria and viruses elicit a Th1-mediated immune response, which down-regulates Th2 responses. • Insufficient stimulation of the Th1 arm, leads to an overactive Th2 arm, stimulating the antibody-mediated immunity of the immune systems, which leads to allergic reactions within the body. • The major proposed alternative mechanistic explanation of the rise in autoimmune dieseases is that the developing immune system must receive stimuli (from infectious agents, symbiotic bacteria, or parasites) in order to adequately develop regulatory T cells. Expansion of theory. • It can be put simple layman terms that the immune system needs training i.e exposure to forgein bodies to work properly , due to modern practises of elminating all bacteria where possible (e.g pasteuration of milk) has meant that in devolped countries both allergic and autoimmune dieseases have increased signifcantly. • H. pylori has been with humanity since before we left Africa. In days of old, when humans routinely encountered H. pylori early in childhood, the bug taught their immune cells tolerance and protected against asthma. Now, since we grow up in cleaner environments, we encounter it later. Not only does its early absence predispose to asthma, its late introduction induces ulcers. • It is proven that H pylori protects against heartburn, esophageal cancer, asthma, and eczema.* Outcomes Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms. Supporting Evidence “The Hygiene Hypothesis originated with earlier experiments with animals, mainly mice and rats born and raised in "germ-free" or sterile environments. When experimentally exposed to low doses of an infectious agent that would not harm normally raised rodents, these germ-free adolescent and young adult animals became infected quickly and often died” Medicine.net Charles P. Davis, MD, PhD Supporting Evidence “Sardinians are an isolated, inbred group, and they have experienced a twin epidemic of multiple sclerosis and type I diabetes, both autoimmune diseases, in the past sixty years—ever since they got rid of malaria. For the past few thousand years, those Sardinians that were genetically resistant to the malaria parasite survived; those that were not did not. The relentless presence of malaria in their environment shaped their genomes.” Velasquez-Manoff- An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases Bilbography • Commentary. The coming-of-age of the hygiene hypothesis Fernando D Martinez http://link.springer.com/article/10.1186/rr48 • http://en.wikipedia.org/wiki/Hygiene_hypothesis • http://www.medicinenet.com/script/main/art.asp?articlekey=155757 • Velasquez-Manoff- An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases • http://www.helpmychronicpain.com/Portals/67234/images/Screen%2 0shot%202011-10-23%20at%2012.09.05%20PM-resized-600.png • http://seekingalpha.com/article/329752-coronado-biosciencesphase-ii-trials-provide-multiple-shots-on-goal • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782226/