医学免疫学课件：I型超敏反应的变应原免疫治疗机制

1、Allergen Immunotherapy and Type I Hypersensitivity: Molecular and Cellular MechanismsContent1. Introduction1.1 Type I hypersensitivity1.2 Immune tolerance1.3 Allergen immunotherapy2. Mechanisms2.1 Innate immunity2.2 Adaptive immunity3. Evaluation of immunotherapy1. Introduction1.1 Type I Hypersensit

2、ivityRole of IL-10Initially as a Th2 cytokineAnti-inflammatory and anti-immune functionMast cell activation by IgETh2 cytokine productionInduction of Th1 and TregRutz, S. and W. Ouyang, Regulation of interleukin-10 and interleukin-22 expression in T helper cells. Curr Opin Immunol, 2011. 23(5): p. 6

3、05-12.1.2 Immune toleranceChinthrajah, R.S., et al., Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol, 2016. 137(4): p. 984-97. TreatmentAnti-histamine therapy and corticosteroid therapyAllergen avoidanceAllergen immunotherapy1.3 ImmunotherapyMatsuoka, T.,

4、 M.H. Shamji and S.R. Durham, Allergen immunotherapy and tolerance. Allergol Int, 2013. 62(4): p. 403-13.Ways to perform immunotherapySubcutaneous immunotherapySublingual immunotherapyDendritic cells in the mucous membraneOral immunotherapy: food allergyEpicutaneous immunotherapyHigh-dose pollen pat

5、ch with heat-labile Escherichia coli toxin2. Mechanisms2.1 Innate immunity: basophils and p38 MAPKWitting Christensen SK, Kortekaas Krohn I, Thuraiaiyah J, Skjold T, Schmid JM, Hoffmann HJH. Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK. Allergy 2014; 69:

6、13431349.Role of p38 MAPKCuadrado, A. and A.R. Nebreda, Mechanisms and functions of p38 MAPK signalling. Biochem J, 2010. 429(3): p. 403-17.2.1 Innate immunity: dendritic cellsDendritic cellsAntigen stimulationDC1Th1DC2Th2DCregTreg2.1 Innate immunity: dendritic cellsGueguen, C., et al., Changes in m

7、arkers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol, 2016. 137(2): p. 545-58.2.1 Innate immunity: dendritic cellsGueguen, C., et al., Changes in markers asso

8、ciated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol, 2016. 137(2): p. 545-58.2.1 Innate immunity: dendritic cellsGueguen, C., et al., Changes in markers associated with

9、 dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol, 2016. 137(2): p. 545-58.2.1 Innate immunity: innate lymphoid cellsNo Rag-dependent recombinant antigen receptorsNo myeloid or

10、dendritic cell markersLymphoid morphologySpits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cellsa proposal for uniform nomenclature. Nat Rev Immunol 2013; 13:145-9.Role of ILC2Lao-Araya M, Steveling E, Scadding GW, Durham SR, Shamji MH. Seasonal increases in per

11、ipheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol 2014;134:1193.2.2 Adaptive immunity: blockingLupinek, C., E. Wollmann and R. Valenta, Monitoring Allergen Immunotherapy Effects by Microarray. Curr Treat Options Allergy, 2016. 3: p.

12、 189-203.2.2 Adaptive immunity: role of FcRII Daron M, Latour S, Malbec O, Espinosa E, Pina P, Pasmans S et al. Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest 1995;95:577585.2.2 Adaptive immunity: internalization of IgEUerms

13、i C, Zabel F, Manolova V, Bauer M, Beerli RR, Senti G, Kndig TM, Saudan P, Bachmann MF. IgG-mediated down-regulation of IgE bound to mast cells: a potential novel mechanism of allergen-specific desensitization. Allergy 2014; 69: 338347.2.2 Adaptive immunity: cytokinesSmaldini PL, Delgado MLO, Fossat

14、i CA, Docena GH. Orally-induced intestinal CD41 CD251 FoxP31 Treg controlled undesired responses towards oral antigens and effectively dampened food allergic reactions. PLoS One 2015;10:e0141116.2.2 Adaptive immunity: TregSmaldini PL, Delgado MLO, Fossati CA, Docena GH. Orally-induced intestinal CD4

15、1 CD251 FoxP31 Treg controlled undesired responses towards oral antigens and effectively dampened food allergic reactions. PLoS One 2015;10:e0141116.2.2 Adaptive immunity: TregSyed A, Garcia MA, Lyu SC, Bucayu R, Kohli A, Ishida S, et al. Peanut oral immunotherapy results in increased antigen-induce

16、d regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol 2014;133:500-10.3. Evaluation of immunotherapyPossible evaluation methodsDetection of blocking antibodiesClinical score of the symptomsDetection of cytokinesMicroarrayLupinek, C., E. Wollmann a

17、nd R. Valenta, Monitoring Allergen Immunotherapy Effects by Microarray. Curr Treat Options Allergy, 2016. 3: p. 189-203.ConclusionsReferences1 Chinthrajah, R.S., et al., Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol, 2016. 137(4): p. 984-97.2Cuadrado, A

18、. and A.R. Nebreda, Mechanisms and functions of p38 MAPK signalling. Biochem J, 2010. 429(3): p. 403-17.3 Daron M, Latour S, Malbec O, Espinosa E, Pina P, Pasmans S et al. Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest 1995;

19、95:577585. 4 Gueguen, C., et al., Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol, 2016. 137(2): p. 545-58.5 Lao-Araya M, Steveling E, Scaddi

20、ng GW, Durham SR, Shamji MH. Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol 2014;134:1193.6 Lupinek, C., E. Wollmann and R. Valenta, Monitoring Allergen Immunotherapy Effects by Microarray. Curr Treat Opt

21、ions Allergy, 2016. 3: p. 189-203.References7 Matsuoka, T., M.H. Shamji and S.R. Durham, Allergen immunotherapy and tolerance. Allergol Int, 2013. 62(4): p. 403-13.8 Rutz, S. and W. Ouyang, Regulation of interleukin-10 and interleukin-22 expression in T helper cells. Curr Opin Immunol, 2011. 23(5):

22、p. 605-12.9 Smaldini PL, Delgado MLO, Fossati CA, Docena GH. Orally-induced intestinal CD41 CD251 FoxP31 Treg controlled undesired responses towards oral antigens and effectively dampened food allergic reactions. PLoS One 2015;10:e0141116.10 Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, et al. Innate lymphoid cellsa proposal for uniform nomenclature. Nat Rev