PARTICLE-CELL INTERACTIONS AND THEIR IMPLICATIONS IN LUNG DEFENSE - PowerPoint PPT Presentation

PARTICLE-CELL INTERACTIONS AND THEIR IMPLICATIONS IN LUNG DEFENSE MECHANISMS Kiama S. G University of Nairobi

PARTICLE DEPOSITION AND CLEARANCE IN THE LUNG DOSE EFFECT EXPOSURE DEPOSITION CLEARANCE RETENSION  Aerodynamic filtration  Mucociliary escalator system  Tight junctions on epithelial cells  Cellular clearance e.g Macrophages (by P. Gehr)

(by P. Gehr)  Macrophages  Dendritic Cells  Epithelial Cells

Dendritic cells & Immunity (Modern Drug Discovery, May/June 1999, pp. 37) Antigen Presenting Cell B7-1/ ICAM-1 B7-2 MHC I/ LFA-3 MHC II  Naive T cells - 10 to 30 hr  Effector T cells -within an hr CD4/CD8 TCR CD2 CD28 LFA-1 T Lymphocyte

by P. Holt

Culture of Human Dendritic Cells In Vitro (Sallusto and Lanzavecchia, J. Exp. Med. (1994) 179: 1109-1118) GM- GM-CSF CSF, IL-4 IL-4 + LPS Mature Dendritic Cells Human Peripheral Immature Blood Monocytes Dendritic Cells HAM Human Alveolar Macrophages

Mo-DC6 Mo Mo-DC9 HAM

90 30 Phagocytic index in 80 Vo lum e density in 25 70 60 20 50 15 40 30 10 20 5 10 0 0 MO Mo-DC6 Mo-DC9 HAM Mo Mo-DC6 Mo-DC9 HAM

Interaction of Dendritic Cells with Salmonella Typhimurium . Bacterium TH1 Cell mediated immunity Phagosome CD4+ MHC II CD8+ MHC I TH2 Humoral mediated immunity

S. typhimurium induce maturation of DC on infection

Apoptosis of dendritic cells

Membrane ruffling of Dendritic cells

Spacious phagosome

Microvesicles? Apoptotic bodies?

APOPTOSIS AND MICROVESICLES APOPTOSIS RELEASE OF VESICLES

HARVESTING OF RESPIRATORY MACROPHAGES FROM THE CHICKEN AND THE RAT

NUMBER OF HARVESTED RESPIRATORY MACROPHAGES X 1000,000 0 1 2 3 4 5 6 7 8 RAT CHICKEN

Uptake of Particles by Macrophages

COMPARISON OF PHAGOCYTOSIS BETWEEN CHICKEN AND RAT RESPIRATORY MACROPHAGES PHAGOCYTISED PARTICLES 30 VOLUME FRACTION OF 25 20 15 10 5 0 CHICKEN RAT

AVIAN ERYTHROCYTES ARE PHAGOCYTIC

 Uptake of particles by chicken erythrocytes

Uptake of particles by chicken epithelial cells

Acknowledgements  Peter Gehr  Laurent Nicod  John Maina  Don Dreher  Barbara Rothen University of Nairobi, Kenya  Meno Kok  Calorina Obregon University of Bern,  Laurence Cochand Switzerland University of Witwatersrand, South Africa