Leishmania Flashcards
Leishmania overview
- transmitted by sand flies
- 400,000 a year incidence rate
- 12M cases worldwide
- can be fatal, epidemiologically diverse and complex
- obligate intracellular parasites
- live in cells of macrophage lineage
Where can Leishmania be found?
In the old world (Mediterranean, central Asia, west and east Africa
New world (central America and northern south America)
How do sand flies transmit Leishmania
the parasites block the mouthparts of the fly, in order to take a proper meal the sand fly has to regurgitate its gut contents to remove the blockage
what does meta-cyclic mean
produced in intermediate host and infective for the definitive host
E.g., Leishmania
Leishmania infection mechanism
macrophage is the first line of defence, and Leishmania want to enter the cells of the reticuloendothelial system (macrophages). It is why some species of Leishmania prefer to live in macrophages not on the skin, but in liver of spleen
What does the infected stage of Leishmania look like
a flagellated promastigote
20-25µm
What are the three types of molecules present on the Leishmania surface
Family of glycoinositol phospholipids (GIPLS)
Lipophosphoglycan (LPG)
Glycosyylphosphatidylinositol anchored glycoproteins (GP63)
What does Gipls do
Imbedded in the membrane
More of them than LPG
What does LPG do
Inositol lipid anchor, repeating saccharide units, component of glycoalyx
GP63
major one is a surface protease of mol weight 63kDa
What system do we use to recognise foreign substances
The complement system
- A series of proteins activated upon recognition of something foreign
- series of serum proteins made in liver
- exist as precursors
- once activated –> active enzyme
What are the functions of the complement system
- Opsonisation - complement receptors on cells
- Cell lysis - lytic sequence
- Chemotaxis and inflammation - small fragments
Why isn’t Leishmania destroyed?
- it increases thickness, elongate LPG from non-infective to infective stages - stops MAC forming
- sheds LPG
- GP63 increases expression
basically molecules have multiple functions, to help protect the parasite from being destroyed
Why don’t macrophages engulf Leishmania?
It can adapt the vacuole to change the pH (4.2-5.2)
- LPG inhibits lysosomal enzymes and PLC
- GP63 inactivates host proteases
What happens when neutorphils try to destroy Leishmania
1st on the scene
they take it up 1st, apoptose and either release parasite, or are taken up by macrophages (TROJAN HORSE)
