Most allergens are immunologic inert proteins that typically do not induce inflammatory responses but allergen specific tolerance. However, the presence of so called danger toward signals such as proteolytic Inhibitors,Modulators,Libraries enzyme Inhibitors,Modulators,Libraries activity of allergens themselves or microbial antigens leads to DC activation. Particularly, DCs express pattern recognition receptors such as Toll like receptors for microorganism associated molecular patterns that are invariant and consistent molecular structures of bacteria and other microorgan isms. PPR activation induces MAMP dependent signal transduction and activation of transcription factor nuclear factor kB and of MAPK, followed by transcription of proinflammatory cytokines such as tumour necrosis factor a, IL 6, und IL 12 and expression of costimulatory Inhibitors,Modulators,Libraries molecules such as CD40 and CD80CD86.

Regular development of the immune system and the balance of adaptive Th1 Th2 immune responses is probably based mainly on natural exposition to microbial antigens as TLR ligands Inhibitors,Modulators,Libraries via the gastrointestinal tract, skin, and airways or on several infectious diseases during early infancy and childhood. A variety of immunomodulatory prevention concepts attempt to reconstitute the natural balance of the adaptive immune response by specific activation of PPRs by means of microbial antigens. Mycobacterial Antigens Mycobacterial antigens such as lipoproteins activate TLR 2 in complex with TLR 1 and TLR 6 or TLR 4. induce production of IL 12, TNF a, IL 10, and IL 15. and initiate development of Th1 effector cells.

35 In numerous mouse models, vaccination with live or inactivated pathogenic or apathogenic Mycobacteria prevented development of aller gen mediated sensitization and airway inflammation. 3639 Recent clinical trials showed a therapeutic effect such as subcutaneous injection of heat inactivated Mycobacteria bovis bacille Calmette Gue��rin on pre existing asthma in adults40 Inhibitors,Modulators,Libraries or intradermal application of Mycobacterium vaccae on moderate or severe atopic eczema in children. 41 Nevertheless, primary download the handbook preventive effects of Mycobacteria on atopic diseases in humans need to be further investigated. CpG motifs Unmethylated cytosine guanine dinucleotides are common components of prokaryotic bacterial or viral DNA. they are also synthetically produced. CpGs are incorporated by DCs via endocytosis. they bind and activate cytosolic TLR 9 and induce activation of NF kB, followed by secretion of type I interferons, IL 12, IFN inducing protein 10, and other cytokines and chemokines. The resulting innate Th1 immune response is short and limited to proliferating T cells. it is not able to modulate memory Th2 cells. 34 Further, CpG motifs activate the tryptophan degrading enzyme indolamine 2,3 deoxygen ase via the STAT1 pathway in CD19 DCs.