AllergyPPT-UniversityofLeicester.pptVIP

516bp 516bp PMA/Ionomycin Inhibitors - - + + + + - - b-actin IL-13 Protease Inhibitors Do Not Prevent Cytokine mRNA Expression by KU812 516bp b-actin IL-13 - - - + PMA/Ionomycin Tetanus toxoid - - - + - + -ve 516bp Time (hr) 1 1 4 4 4 Non-Proteolytic Antigens Do Not Induce Cytokine mRNA Expression by KU812 Der p1 induces IL-4 and IL-13 protein expression in Freshly isolated Basophils 516bp 516bp 516bp 516bp 516bp b-actin IL-4 IL-5 IL-13 IFN-g - Inhibitors + Inhibitors -ve +ve 0 ES 100ng/ml ES 200ng/ml ES 1000ng/ml ES 0 ES 100ng/ml ES 200ng/ml ES 1000ng/ml ES Necator Americanus Proteases Induce Type-2 Cytokine Expression by KU812 Der p1 and hookworm excretory/secretory products induce IL-4 and IL-13 protein expression in KU812 Basophils The switch to IgE Lebman Coffman 1988 J Exp Med 168, 853-862 Ca2 Ce Cg4 Cg2 Ca1 Cg1 Cg3 Cd Cm Switch regions The Sm consists of 150 repeats of [(GAGCT)n(GGGGGT)] where n is between 3 and 7. Switching is mechanistically similar to V(D)J recombination. Sg3 Sg1 Sa1 Sg2 Sg4 Se Sa2 Sm Switch regions - repetitive regions of DNA that physically recombine Upstream of C regions Cm Cd Cg3 VDJ Cg3 VDJ IgG3 produced. Switch from IgM Switch recombination to IgE A three signal process: Antigen – controls entire process Soluble help via IL-4 or IL-13 from T helper cells Cognate help via CD40 L from T helper cells Y Y Y T cell help to B cells B Antigen Th Th IL-4 and IL-13 CD40 Ligand CD40 Switch recombination to IgE A three signal process: Antigen Soluble help via IL-4 or IL-13 from T helper cells Cognate help via CD40 L from T helper cells Stat-6 P Stat-6 P Soluble help via IL-4 or IL-13 from T helper cells IL-4Ra IL-4Ra gC IL-13Ra1/2 IL-13 IL-4 IL-13 IL-4 IL-4R IL-13R JAK1 JAK3 TYK1 JAK1 TYK2 P P Stat-6 P Stat-6 P P P Stat-6 P P Stat-6 P P Stat-6 P P P Dimerised Stat-6 translocates to nucleus Switch recombination to IgE A three signal process: Antigen Soluble help via IL-4 or IL-13 from T helper cells Cognate help via CD40 L from T helper