Natürliche und adaptive immunität des respirationstraktes - Bedeutung mikrobieller faktoren für infektabwehr und sensibilisierung - Teil II

Translated title of the contribution: Innate and adaptive immunity of the respiratory tract - The role of microbial factors for host defense and sensitization - Part II

W. König, H. Lauf, U. Arnold, I. Tammer, B. Ghebremedhin, A. Clarici, F. L. Thies, A. Drynda, A. Schmalcz, T. Kwok, R. Arnold, S. Backert, H. Werchau, B. König

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Under the "umbrella" of various inflammatory signals, the dendritic cells on interaction with exogenous compounds, e.g. bacteria, viruses, allergens, pollutants, mature and transmit the signal to the peripheral lymph node, thus interacting and tuning diverse effector T cells. The result of this is under a control of T-regulatory cells which either allows the dichotomy of TH1- or TH2-induced cellular functions with the generation of IL-2 and Interferon-γ for Th1 or IL-4, IL-5, IL-13, IL-10 for Th2. Clearly, the opposite action does not necessarily imply protection or damage but is the result of the appropriate response in host defense either allowing a humoral or cell-mediated immune response. Obviously, when outbalanced inflammatory and allergic disease processes may occur, which in rare cases are exclusively either TH2- or TH1-directed. Basically, the majority of reactions finally shows a complex mixture of TH2 and TH1 processes as is observed in allergy, asthma as well as atopic dermatitis. The respiratory tract in contrast to the gastrointestinal tract clearly shows differences with regard to the efficacy of T effector cell function. In the gastrointestinal tract, the T-regulatory system seems to be overwhelming primarily in the response as far as antigens and allergens are concerned leading to a status of tolerance. This is obligatory in order to comply with the huge commensal microbial flora which is present in the intestinal lumen. The pathogenicity within the gastrointestinal lumen is certainly a result of defined microbial pathogenicity factors or a deficiency of the commensal flora within the lumen which has protective functions. Within the respiratory tract, additional mechanisms are operative which are supported by components of the innate immune system within the surfactant system or other structures which may eliminate the influx of allergens, antigens and microorganisms. The protective cellular function is often overridden by the fact that the majority of allergens also have protease activities and there is indication that a basic general enzyme activity (chitinase) might be the clue to allergy. Protease-associated allergens induce inflammatory mediators from mast cells, thus providing histamine, leukotrienes and cytokines which tune the effector T cell function to a TH2 profile with the predominant release of IL-4 and IL-5. This then allows the induction of IgE responses and eosinophil activation, which most likely is not necessarily associated with asthma. Basically, IgE is not only regarded as the bridging molecule for the induction of mast cell mediator release. By the diversity of various receptors for IgE, an amplified inflammatory response via FcεRI and FcεRII on interaction with allergens and antigens may occur. In addition, the occurrence of IgE also modulates structural functions of the IgE receptor and initiates the generation of inflammatory mediators and the increase of e.g. cellular histamine content. The detailed studies on inflammatory mediators, such as histamine, prostaglandins and leukotrienes, clearly led to the identification of receptors for these molecules which are 7 transmembrane G-protein-coupled receptors. By their presence on various cells and their diversity, a single mediator such as histamine can either activate or downregulate the inflammatory processes by induction of e.g. IL-10 or TGF-β.

Translated title of the contributionInnate and adaptive immunity of the respiratory tract - The role of microbial factors for host defense and sensitization - Part II
Original languageGerman
Pages (from-to)605-620
Number of pages16
JournalAtemwegs- und Lungenkrankheiten
Volume30
Issue number12
Publication statusPublished - Dec 2004
Externally publishedYes

Keywords

  • Asthma
  • Atopic dermatitis
  • Chemokines
  • Cytokines
  • Defensins
  • Eosinophils
  • Epithelial cells
  • Histamine
  • Innate and adaptive immunity
  • Leukotrienes
  • Mast cells
  • TH1/TH2 dichotomy
  • Tissue remodelling
  • Toll-like receptors
  • Tr-regulatory cells

Cite this