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11-2-09 Immune Responses II: Immunology of allergic disease and asthma 1.

Hygiene hypothesis The hygiene hypothesis states that children exposed to other children or animals early in life are exposed to more microbes, and their immune systems de elop more tolerance for the agents causing asthma, allergies, and s!in disorders" The human immune system can be described as ha ing t#o types of biological defenses" $hen one type of defensi e system lacks practice in defending against bacteria or iruses %as a conse&uence of a sanitary lifestyle', the other system overreacts to harmless substances li!e pollen" The hygiene hypothesis #as de eloped based on obser ations of urban s rural, farming s nonfarming, and early exposure to parasites, allergens, and iruses" (ome en ironmental factors that promote allergic disorders include: )eing in a #esterni*ed country (mall family si*e +ffluent, urban homes Intestinal microflora that,s stable -igh antibiotic use .o# or absent helminth burden /ood sanitation0 lo# orofecal burden 2. Allergic asthma etiology and prevalence +sthma is an immunological disease dri en by Th2 helper T cells" It is a complex trait that in ol es )1T- heritable and environmental factors" 2eople ha e a genetic predisposition to asthma and, upon encountering an allergen, is induced to endure an inappropriate immune response in ol ing Th2 cytokines" The Th2 response generates air#ay inflammation %bronchoconstiction' that is a culmination of effects from Th2 cells, mast cells, and eosinophils" The reduced air#ays cause #hee*ing, coughing, and chest tightness, the characteristic symptoms of asthma" +sthma is a disease of ci ili*ation and has risen steadily since the 1930s and is more pre alent in $estern nations" There is no cure, and treatments focus on alle iating symptoms" 3. Cells that participate in allergic disease and asthma, their role and what they produce: B cells ) cells perform three functions after encountering antigen: 1' it presents the antigen to helper T cells ia 4-5 5lass II molecules and 2' it proliferates and undergoes antibody class s#itching to secrete IgE and 6' differentiates into plasma cells and memory cells" Ig7 goes on to acti ate mast cells %see belo#'

T cells

Th2 cells secrete a host of cyto!ines #ith the follo#ing effects: I.-6gro#th of progenitor hematopoeitic cells /4-5(8myelopoiesis %formation of myeloid lineage cells' IL-4) cell acti ation and gro#th, Ig7 class s#itching, induction of 4-5 5lass II, macrophage inhibition IL-5eosinophil gro#th IL-6) cell gro#th IL-10inhibit macrophage acti ation, inhibit Th1 cells T !-betainhibits macrophage acti ation IL-1"directly affect lung smooth muscle %air#ay obstruction'

!T cells 9:T cells express cell surface mar!ers similar to 9: and con entional T cells, recogni*ing #g$%&1' %they recogni*e glycolipid antigens presented by 4-5 class I-li!e protein 5;1d' and produce abundant cyto!ines upon acti ation" "osinophils 7osinphils secrete granule proteins that are cationic to(ins that 'isr)pt membranes" 9ormally, they function in combating helminthic parasites and bacteria" In allergy, granule proteins are toxic to cells from numerous organs, including bronchiole epithelium, !eratinocytes, pneumocytes, and gut epithelium" 7xamples of granule proteins include ma<or basic protein %4)21', eosinophil-deri ed neurotoxin %7;9', eosionphil cationic protein %752', eosinophil peroxidase, and 4)2 homolog %4)22'

#ast Cells 4ast cells contain granules full of histamine and heparin and are located close to body surfaces such as the s!in, #alls of the intestines, and air#ays" In allergy, IgE bin's to !c*+I receptors #ith high affinity %only 10= occupancy of receptors is re&uired for 'egran)lation'" ;egranulation releases a host of inflammatory molecules: ,istaminesmooth muscle contraction, increased ascular permeability, irritation -ininssmooth muscle contraction, inflammation, irritation .roteasesdamage tissues and acti ate complement Le)kotrienesslo# prolonged smooth muscle contraction .rostaglan'inseither contract or relax smooth muscle Basophils .i!e last cells, basophils store histamine and can degranulate upon stimulation"