giardia and cell biology Flashcards
1
Q
giardia evolution
A
- parasitic protozoa
- primitive eukaryotes
- no mitochondria
- 2 transcriptionally active nuclei
- unknown why
2
Q
giardia intestinalis
A
- parasite of small intestine
- causes giardasis - diarrhoea and vomiting
- fecal oral transmission
- drinking contaminated water
- can persist asmptomatically for many years
- dormant cysts persist in environment for a long time
- spread by faeces
- ingestion of 10 cysts is enough to cause infection
3
Q
giardia lifecycle
A
- human ingests dormant cyst
- thick wall of cyst protects it
- low stomach pH triggers excystation
- differentiation into metabolically active trophozoite in small intestine (higher pH)
- attaches to cell wall of small intestine with adhesive disc and causes infection
4
Q
giardia cysts
A
- dormant environmental transmission stage
- egg-shaped
- down-regulated metabolism
- persists in cold water for months
- undergoes organelle duplication without cytokinesis
- produces 4 nuclei, medianbodies and axonemes
- each cysts produces 2 trophozoites upon excystation
5
Q
giardia trophozoites
A
- disease causing stage
- can’t survive in environment
- flat, 10-12 microns long
- pear shaped with bilateral symmetry
- 5-7 microns wide
- large sucking disc on anterior ventral side
- 4 pairs of flagella
- 2 diploid nuclei - 2 x 2n
- no mitochondria or golgi bodies
6
Q
giardasis
A
- giardia attach to small intestine in large numbers
- compete for nutrients and impair host uptake
- leads to diarrhoea and vomiting, and eventually malnutrition
7
Q
mitosomes
A
- small double membrane bound organelles
- mitochondrial relics with mitochondrial proteins
- 25-100 per cell
- giardia generate ATP in the cytosol using FeS clusters synthesised in mitosomes
8
Q
giardia and mitochondria
A
- thought to have initially had mitochondria
- lost at some point as no longer necessary
- living in host means they could jettison certain structures
- important for drug development - can’t target mitochondria
9
Q
antigenic variation of giardia
A
- clonal phenotypic variation
- single varying surface molecule expressed at a time
- parasite switches between various epitopes to evade host immune system recognition
10
Q
requirements for antigenic variation
A
- family of homologous genes encoding an immundominant, antigenically different surface molecule
- or process that generates diversity in this molecule
- mechanism which guarantees mutually-exclusive expression of one antigen at a time
- mechanism for reversibly switching expression of these moelcules in individual cells
11
Q
evidence for AV in giardia
A
- previous exposure provides immunity
- if reinfection occurs symptoms are less severe
- when grown in vitro, surface appears to change
- grow with antibodies - after time can’t bind surface
- monoclonal antibodies - show variants exist
12
Q
VSPs
A
- variant-specific surface protein
- very dense protective coat that covers giardia surface
- TM domain in plasma membrane, rest projects out
- shields invariant molecules on cell surface
- cells have very large gene family of these proteins
- antibodies against VSPs are cytotoxic if host has enough time to produce them
13
Q
VSPs structure
A
- variable N-terminal domain
- semi-conserved C-terminal domain (much less variable)
- 23-25 aa TM domain
- invariant CRGKA cytoplasmic tail
14
Q
features of VSP sequences
A
- cysteine-rich with many CXX motifs
- frequently glycosylated
- probably everged covergently with VSGs of African trypanosomes
- very similar structure
15
Q
AV during chronic infection
A
- only 1 VSP expressed at a time (mutually exclusive) and coats whole surface
- expressing more than 1 will immunise host to multiple variants
- switching every 6-13 generations
- occurs spontaneously - doesn’t require presence of an immune system
- must occur before host has enoguh time to produce sufficient numbers of antibodies
- no evidence of gene rearrangements
- unlike african trypanosome
