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

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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

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PARTICLE-CELL INTERACTIONS AND THEIR IMPLICATIONS IN LUNG DEFENSE MECHANISMS

Kiama S. G University of Nairobi

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PARTICLE DEPOSITION AND CLEARANCE IN THE LUNG

EXPOSURE DOSE EFFECT RETENSION DEPOSITION

CLEARANCE

 Aerodynamic filtration  Mucociliary escalator system  Tight junctions on epithelial cells  Cellular clearance e.g Macrophages

(by P. Gehr)

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Macrophages Dendritic Cells Epithelial Cells

(by P. Gehr)

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Dendritic cells & Immunity

LFA-1 CD4/CD8 TCR CD2 CD28 ICAM-1 MHC I/ MHC II LFA-3 B7-1/ B7-2 Naive T cells - 10 to 30 hr  Effector T cells -within an hr

T Lymphocyte

Antigen Presenting Cell

(Modern Drug Discovery, May/June 1999, pp. 37)

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by P. Holt

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Culture of Human Dendritic Cells In Vitro

(Sallusto and Lanzavecchia, J. Exp. Med. (1994) 179: 1109-1118)

Immature Dendritic Cells Mature Dendritic Cells GM-CSF IL-4 GM- CSF, IL-4 + LPS Human Peripheral Blood Monocytes

HAM

Human Alveolar Macrophages

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Mo Mo-DC6 HAM Mo-DC9

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5 10 15 20 25 30

MO Mo-DC6 Mo-DC9 HAM Vo lum e density in

10 20 30 40 50 60 70 80 90

Mo Mo-DC6 Mo-DC9 HAM Phagocytic index in

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Interaction of Dendritic Cells with Salmonella Typhimurium.

CD4+ TH2

MHC I MHC II

TH1

Bacterium

Phagosome CD8+

Cell mediated immunity Humoral mediated immunity

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S. typhimurium induce maturation of DC
n infection

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Apoptosis of dendritic cells

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Membrane ruffling of Dendritic cells

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Spacious phagosome

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Microvesicles? Apoptotic bodies?

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APOPTOSIS AND MICROVESICLES

APOPTOSIS RELEASE OF VESICLES

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HARVESTING OF RESPIRATORY MACROPHAGES FROM THE CHICKEN AND THE RAT

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

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Uptake of Particles by Macrophages

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COMPARISON OF PHAGOCYTOSIS BETWEEN CHICKEN AND RAT RESPIRATORY MACROPHAGES

5 10 15 20 25 30 CHICKEN RAT VOLUME FRACTION OF PHAGOCYTISED PARTICLES

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AVIAN ERYTHROCYTES ARE PHAGOCYTIC

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Uptake of particles

by chicken erythrocytes

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Uptake of particles by chicken epithelial cells

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Acknowledgements

 Peter Gehr  Laurent Nicod  John Maina  Don Dreher  Barbara Rothen  Meno Kok  Calorina Obregon  Laurence Cochand

University of Nairobi, Kenya University of Bern, Switzerland University of Witwatersrand, South Africa