Vl 4 Leishmania

Question 1

Historically people immunized against a Leishmanial disease. Which species was targeted, and how does the vaccination work?

Answer 1

wilfully induced infection of young women at upper leg (muslims), no follow up infections in the face (first infection leaves visible marks)
⇒ L. tropica
vaccination with living, virulent parasites induces immunity against reinfection

Question 2

Which host cells are invaded by Leishmania, and how does host cell invasion occur? Describe the course of infection after transmission by an infected Phlebotomus sandfly.

Answer 2

• neutrophils and macrophages are targeted
  ⇒ Trojan-horse-theory: neutros are the first ones at biting site, take them up, are prolonged apoptotic by parasite and taken up in disguise by macrophages
• has ONE ULTIMATE receptor for host fibronectin, mannose and complement factors ⇒ protease on surface cleaves C3 ⇒ presented to macros complement CR1 and CR2 receptors ⇒ phagocytosis

Question 3

Which immune factors contribute to: i) recovery of versus ii) chronic cutaneous lesion after inoculation with e.g. Leishmania brasiliensis?

Answer 3

• Recovery: cytokines from TH1 (e.g. IL-12, TNF and IFN-gamma) cause inflammation ⇒ strong T-cell response and IFN-gamma production
• Chronic: immune factors from TH2 (e.g. IL-4/5/13) ⇒
  no T-cell reaction, no IFN-gamma-production ⇒ macros stay infected

Question 4

How does Leishmania manipulate its Phlebotomus vector thereby increasing transmission success?

Answer 4

• chitinolysis (destruction) of the phagusvalve (located between pharynx and midgut)

⇒ constant mix up of saliva and blood, makes sucking less effective ⇒ fly has to bite more often to get proper blood meal ⇒ more chances for parasites to enter host

Question 5

Describe the life cycle of Leishmania in the vector and mammaiian host

Answer 5

1) Sandfly injects promastigotes
2) attach to phagocytes, get taken up, proliferate as amastigotes and lyse the cell to reinvade other host cells or be taken up again by another sandfly, proliferating there attached to the gut wall
3) conversion to promastigotes (extracellular in vector, intracellular in host)