Protists and disease Flashcards
Protists are
All eukaryotic organisms that are neither animals, nor plants, nor fungi
What are the challenges of living within blood?
- Innate immune response
- Adaptive immune response
- Low Iron conc
- How to infect next host
All trypanosomes have a stage in
Vertebrate blood
Structure of a typanosome (kinetoplastid)
Kinetoplast (like a mitochondrion)
Nucleus
Flagellum
Trypanosomes can infect
A wide variety of vertebrates
Wide variety of vectors
Vectors transmit
The parasites to the hosts
T. Brucei causes
African Sleeping Sickness
Human Trypanosomiasis
T. brucei is transmitted by the
Tstetse fly
T. brucei does not have
A free living stage
T. brucei hosts include
Livestock animals as well as humans
T. brucei life cycle
- Tsetse fly bites and takes up trypanosome
- Trypanosome multiplies in midgut and moves to salivary duct
- Tsetse fly transmits trypanosome during feeding through saliva
T. brucei disease progression stage 1
- Chancre (skin lesion forms) - parasite enters the blood
2. Intermittent fever and headache as trypanosome multiplies
T. brucei disease progression stage 2
- Moves to the CNS
- Produce toxins that disturb sleep and behaviour
- Seizures-coma-death
T. brucei disease stages
Chancre - Fever/Headache - CNS/Sleeping/seizures/coma/death
T. brucei evades the immune system by
Antigenic variation (variant surface glycoprotein VSGs)
VSGs
Variant surface glycoproteins (on outer cell wall)
trypanosome changes expression of these genes and evades detection
Waves of fever and headache are due to
Antibody responses to the changing VSG coats
There are over 1000 VSG genes but
Only one is expressed at any one time
There are 20 VSG expression sites on telomeres (the ends of chromosomes) but
Only one is expressed at any one time
VSG gene switching is
Spontaneous
Occurs every 100 cell doublings
VSG gene switching involves
DNA arrangements or transcriptional regulation
T. cruzi causes
Chagas disease
The vector of T. cruzi is
Triatomine bug
T. cruzi affects
8M people
T. cruzi lifecycle
Feeds on infected blood
Trypanosome develops into infective form in triatomine hindgut
Infected form in faeces
Bites get itchy, infected faeces on hands
Rub eyes
Into bloodstream
T. cruzi first infects
Mucous membranes
Then enter bloodstream
T. cruzi stages of disease
Acute - fever (8-12 weeks)
Chronic - cardiac and intestinal lesions (10 years)
T. cruzi survives in the cytoplasm of
Macrophages, heart cells, epithelial cells, muscle cells and gut cells
Chronic infection occurs in
30% of infections
T. cruzi can cause
Cardiac arrhythmia and mega colon
T brucei contains
Kinetoplast
Invades CNS
Infective saliva
Always fatal
T cruzi contains
Kinetoplast
Invades heart and gut cells
Infective faeces
Sometimes fatal
Malaria is an
Apicomplexan parasite
The Apicomplexa are
Unicellular and spore forming
Hippocrates first described malaria in
500 BC
Agostino Salumbrino observed the bark of the cinchona tree (quinine) was effective against the fever in 1564
The malaria parasite was discovered in
1880
1897 Ross discovered female mosquitos transmitted malaria
Chloroquine was discovered in
1934
Malaria deaths per year
1.5 million
82% deaths in children in sub saharan africa (mainly cerebral malaria, P falsiparum
P. falsiparum life cycle
Sporozoites injected with saliva
Invade Kupffer cells (macrophages in liver)
Invade hepatocytes (divide asexually into schizonts)
Hepatocyte-schizont ruptures and releases merozoites into blood
Merozoites invades RBCs then turn into
Trophozoites OR Schizonts
Trophozoites eat RBC cytoplasm
Schizonts replicate asexually and then merozoites erupt and infect new RBCs
Some parasites enter a sexual cycle and form the infective micro or macrogametophytes
Schizonts replicate
Asexually
Nuclear division WITHOUT cytoplasmic division - merozoites
Plasmodium initially infects
Kupffer cells in liver
Schizonts form in
Hepatocytes and RBCs
Plasmodium life cycle summary
Sporozoites - Schizonts - Merozoites - Trophozites/Schizonts
Micro/Macrogametophytes
Malaria is associated with regular episodes of
Fever
When the merozoites are released into the blood
Advantages of living within a RBC
Rigid, resists shear stress
Disadvantages of living within a RBC
Nutrient poor
Short cell life
Continuously exposed to liver and spleen and so immune system
Plasmodium modifies the RBC
Form new channels for import and export of nutrients
Break down Hb into a.a.
Adhesive proteins on surface to avoid clearance by host (clumping and adherence to endothelium)
PfEMP-1
P.f. erythrocyte membrane protein 1
Makes Knobs on surface
Knobs induced by the parasite on the surface of RBC act as
Ligands
Bind to receptors on endothelium
VAR genes encode for different
PfEMP-1 molecules
There are 50 VAR genes but
Only one expressed at any one time
In plasmodium there is a distinct expression site that can only
Accommodate a single var gene promotor
VAR genes that are not being used are silenced in
Heterochromatin and promotor binding proteins
Plasmodium parasites have a
Memory
Enables them to express different VAR genes at each peak of parasthemia
Expression of one VAR gene tends to last for
Many cell cycles
About 1-2 years
