Malaria binding of malaria parasites to host cells
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“MALARIA” Binding of Malaria Parasites to Host cells. Advanced cell biology II, class presentation Kedar Ghimire, April 5, 2006. EM of a plasmodium. Why do we need to concern about Malaria and the tiny mosquito?. Infects 200-300 million people every year! Kills 1-3 million people!!!

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“MALARIA” Binding of Malaria Parasites to Host cells

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Malaria binding of malaria parasites to host cells

“MALARIA”Binding of Malaria Parasites to Host cells

Advanced cell biology II, class presentation

Kedar Ghimire,

April 5, 2006

EM of a plasmodium


Why do we need to concern about malaria and the tiny mosquito

Why do we need to concern about Malaria and the tiny mosquito?

  • Infects 200-300 million people every year!

  • Kills 1-3 million people!!!

  • Kills one child every 30 seconds!!!!!


Brief history of malaria

Brief History of Malaria

  • Originated in Africa

  • In 1898, Ronald Ross discovered plasmodium in Anopheles mosquitoes

  • In past, common in the whole world and mostly in Rome, name derived from the Italian (male-aria)


Malarial parasite

Malarial parasite

  • Caused by four species of Plasmodium

  • Transmitted by any of 60 species of Anopheles among 400 species

  • Plasmodium Falciparum- the most dangerous species and luckily ,the intensely studied one


Life cycle of plasmodium

Life cycle of Plasmodium

  • The life cycle of Plasmodium is extraordinarily complex

Life cycle of Plasmodium Falciparum


Binding of parasite to mosquito cells

Binding of parasite to mosquito cells

  • Parasites tend to attack specific tissues of mosquito

  • Hypothesis, specific ligands- specific receptors binding

  • Specific recognition event, evidence is there to support it.

  • Sporozoites have surface protein called CS protein and TRAP.

  • The protein Saglin- a salivary-gland receptor for parasites (its ability to bind the sporozoite surface protein TRAP

  • Laminins expressed in the midgut epithelial cells thought to bind malaria parasites


Merozoite invasion of red blood cells

Merozoite invasion of red blood cells

Apical adhesion

Bannister et al., 1975, Parasitology, 71, 483-491


Binding of parasite to mammalian host cells

Binding of parasite to mammalian host cells

  • Plasmodium sporozoites successfully invades liver

  • They also express a surface protein CS and TRAP(SSP2)- sporozoite ligands, (STARP, LSA-3)

  • CS binds to hepatocyte microvilli on HSPG and CSPG


Malaria binding of malaria parasites to host cells

Change in Rbc‘s shape: knob formation

Entry into red blood cells


Possible explanation for binding of sporozoites to hepatocytes

Possible explanation for binding of sporozoites to hepatocytes

http://trc.ucdavis.edu/mjguinan/apc100/modules/Digestive/mammal/liver5/liver.html


Plasmodium and problems for immune system

Plasmodium and problems for immune system

  • Toxins released during growth, reproduction or rupture of red blood cells

  • Malaria parasites hide from immune system (Nature, 2005)

  • Plasmodium falciparum constantly changes the appearance of a protein pfEMP1 it deposits on infected RBCs

  • They mainly damage Red blood cells


Prospects for anti malarial vaccines drugs genetic methods

Prospects for Anti malarial vaccines, drugs, genetic methods????

  • Anti-malarial vaccines- not yet

  • Chloroquine, mefloquine etc- resistance and side effects

  • Genetically engineered mosquitoes

  • Organisations funding the malarial research- UNDP, WHO, The Wellcome trust, Gates foundation etc


References

THANK YOU ALL FOR YOUR KIND ATTENTION,

QUESTIONS?

References

  • Sultan AA, Molecular mechanisms of malaria sporozoite motility and invasion of host cells,1999, Int Microbiol

  • Cerami C. et al (1992), The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein, Cell, Cell press

  • Kappe S. et al (2001), Exploring the transcriptome of the malaria sporozoite stage , PNAS

  • Fidock DA, Bottius E, Brahimi K, Moelans II, Aikawa M, Konings RN, Certa U, Olafsson P, Kaidoh T, Asavanich A, et al.,1994, Mol Biochem parasitol

  • Daubersies P, Thomas AW, Millet P, Brahimi K, Langermans JA, Ollomo B, BenMohamed L, Slierendregt B, Eling W, Van Belkum A, Dubreuil G, Meis JF, Guerin-Marchand C, Cayphas S, Cohen J, Gras-Masse H, Druilhe P.et al, 2000, Nature-Medicine

  • http://www.rph.wa.gov.au/labs/haem/malaria/history.html

  • http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/J/Junctions.html

  • http://news.bbc.co.uk/2/hi/health/4419835.stm

  • Consuelo Pinzon-Ortiz. Et al, 2005, The binding of the circumsporozoite protein to cell surface proteoglycans is required for plasmodium sporozoite attachment to target cells, J. Biol. Chem

  • http://www.bio.davidson.edu/Courses/Immunology/Students/Spring2003/Lafontaine/malariawebpage.htm

  • http://en.wikipedia.org/wiki/Chloroquine

  • http://www.wellcome.ac.uk/en/malaria/TheParasite/pfantv1.html

  • http://www.anobase.org/embo_meeting/2005/abstracts/JacobsLorena.pdf


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