Leishmania

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Presentation Transcript

Fun with Flagellated Friends: 

Fun with Flagellated Friends Leishmania – Life cycle and social impact

Vector – The Female Sandfly: 

Vector – The Female Sandfly

Reservoir Hosts: 

Reservoir Hosts Foxes, Jackals, Rodents, Wolves, Chickens, Horses And most importantly-- DOGS

Two Life-cycle stages: 

Two Life-cycle stages Promastigote -elongated, with flagella (10-20 µm long) -occur extracellularly in the insect midgut -motile Amastigote -round (3-7 µm diameter) -occurs intracellularly, during mammalian stage -nonmotile

The Blood Meal (fly becomes vector): 

The Blood Meal (fly becomes vector) Female sandfly bites a host (usually a nonhuman animal), intakes amastigotes through proboscis. Amastigotes reproduce via binary fission and transform in the sandfly’s midgut into promastigotes. How do promastigotes get from the gut back to the proboscis?

Development Inside the Sandfly: 

Development Inside the Sandfly Repeated division blocks the fly gut, resulting in travel forward into the pharynx and blockage of the sucking apparatus Or Chitinolytic enzymes damage the fly cardiac valve, allowing for reverse flow into proboscis

Human Infection (AKA where did I put my insect repellent?): 

Human Infection (AKA where did I put my insect repellent?)

Macrophage Lysis: 

Macrophage Lysis

Macrophage defenses: 

Macrophage defenses Oxidative burst peroxide (H2O2), superoxide anion (O2-) Acidification Enzyme Digestion

Intracellular Survival: 

Intracellular Survival

Leishmania defense mechanisms: 

Leishmania defense mechanisms Produces enzymes to neutralize the oxidative burst of the macrophage. Proton pump to keep the intracellular pH close to neutral. Surface glycoproteins that degrade lysosomal enzymes.

Inactivation of oxidative burst products via enzyme action: 

Inactivation of oxidative burst products via enzyme action Superoxide dismutase O2- + O2- + 2H+  O2 + H2O2 Catalase or trypanothione peroxidase H2O2 + H2O2  O2 + 2H2O

Surface glycoproteins: 

Surface glycoproteins LPG – inhibits oxidative burst; mediates attachment of promastigotes to gut wall. gp63 – degrades lysosomal enzymes

Cutaneous Leishmaniasis: 

Cutaneous Leishmaniasis

Mucocutaneous Leishmaniasis: 

Mucocutaneous Leishmaniasis

Visceral Leishmaniasis: 

Visceral Leishmaniasis

Global Status: 

Global Status