Parasitology
Malaria
Blood disease
Anaemia/cerebral malaria- most deaths are linked to anaemia
3.2 billion people at risk
2-500 million cases a year
1-2 million deaths per year- most are children under 5
Schistosomiasis
Blood fluke
Bilhartzia
Liver failure
1 billion people infected
Constantly laying fertilized eggs
Ascaris
Giant nematode
GI infection
Malnutrition
1 billion people infected
Ectoparasite – lives outside of host
Microparasites
Small
Multiply directly in host- 10^9/10^10 per host
Often cause transient infection- immune response that can clear out the parasite
Results in sterile immunity
Microparasites
, Large
Don’t multiply inside host
Cause chronic infection
Concomitant immunity
Concomitant immunity- the presence of the parasite within the host confers a degree f protection
against superinfection
Outcome is chronic infection and density dependent disease
Malaria has evolved and grown resistance to every malaria drug that has been developed
Why are parasites difficult to control?
Eukaryotic
Large and complex
Complex life cycles
Immune evasion
Eukaryotic
Parasites are eukaryotes
Have a similar structure and metabolism to the host species they infect
Chemotherapy is like cancer chemo
Need to look for unique pathways or structural differences in key molecules
Immunity also relies on identification of unique antigens- structural overlap with host proteins
makes this discrimination difficult
Failure to discriminate self and non-self may exacerbate damage by causing auto immunity
Large and complex
Parasites have thousands of different molecules
Finding a suitable target/ antigen it can be difficult
Macroparasites are physically large and cannot be removed by phagocytosis
Complex life cycles
Parasites often have complex life cycles involving ‘obligate’ passage through a mammalian host
and invertebrate vector
Within each host there are often several distinct life cycle stages, each of which are antigenically
and metabolically distinct
Phagocytosis
Binding via specific receptor subsets
Reactive NO/O metabolites
The plasma membrane derived vacuole is acidified by protein pump
Phagosome lysosome fusion occurs
Particle ingested and destroyed by acid proteases
Host immune response
Some parasites have become adapted to survival in macrophages. In doing this they perturb the
induction of the immune response
Immune evasion example 1
Giardia, malaria, trypanosoma bricei
These have evolved mechanisms of antigenic variation which prevent the host from developing
effective immunity and result in chronic invasion
immune evasion example 3
Toxoplasma gondii and trypanosoma cruzi
, Hide as dormant stages in immunoprivileged sites like muscle, eye or brain and avoid interaction
with the immune response
Adaption to parasitism
Amoeba- pond organism, moves in contact with substrate, hunter/ killer, phagocytic
Entamoeba- human pathogen
Naegleria- soil amoeba, opportunistic human parasite
Entamoeba histolytica
Human pathogen
Directly transmitted gut infection
Amoebic dysentery
Some species cause fatal liver disease
The parasite attacks the gut epithelium forcing its way through
the basement membrane, lysing cells as it progresses
Even macrophages and white blood cells trying to fight infection
are destroyed
In some cases parasite may escape from the gut and form
localised abscesses in the liver- this stage of infection can be
fatal
Entamoeba is adapted to colonise human gut tissue
Upregulated adhesion
Increased phagocytosis
Proteins associated with virulence have been identified
Naegleria
Facultative pathogen which can live for many generations without infecting host
Flagellate trophozoites are thought to enter through the nose during swimming in warm water
and thereafter the brain by locomotion
destruction of neurons causes primary amoebic meningoencephalitis
Adaptions to a parasitic lifestyle
Advantages of a parasitic lifestyle
Unlimited food
, Protection
Transportation
Challenges of a parasitic lifestyle
Immune evasion- must evolve mechanisms to get around immune system
Removal
Transmission- for it succeed it must get to other hosts
Removal blocked in Giardia by attachment
Evolved- concave surface acts as sucker to the animal host’s intestinal epithelial cells
Malaria parasite sequester in capillaries
Malaria parasites in red blood cells would be removed by the spleen
Release proteins to the surface of red blood cell, causing the parasite to adhere to the surface of
capillaries therefore not being removed by the spleen
Hookworms attach to the oesophageal muscles to intestine
Has jaw/ teeth that enables into remain attached to the intestine
Lice attach to hair
Immune evasion-trypanosomes
Have flagella enabling them to swim through the blood stream
They evolve quicker than the immune system can respond
They change their protein coat, changing a single protein, switching to different surface type so
the immune system cant recognise it
Transmission
Direct life cycle (direct transmission)
Indirect- intermediate hosts (vectors)
Direct life cycle
There is direct transmission from host to host
They can have an in-between stage where they are free living
Example of direct transmission of trichomonas
Inhabits urinogenital tract
Transmitted venereally
3.1% of American women and 13.3% of African American women
Aprox 6000 cases a year in UK
Direct transmission of entamoeba histolytica
Found in soil
Faeco-oral transmission
Cause of amoebic dysentery
Synchronising host and parasite life cycles
Sync there life style with their host
E.g. nematodirus battus- hatching delayed till warm spring when susceptible lambs start feeding
E.g. hook worm
Arreseted development in hookworms
1000 million people affected
Remain dormant in host through dry season
Migrate to intestine and mature during rainy season laying masses of eggs
Eggs in faecal mass hatch and larval development starts for new infection
Trichinella kills host
Passage by carnivorism- when the host is killed the meat is then eaten by another possible host
in order for them to passed on
Malaria
Blood disease
Anaemia/cerebral malaria- most deaths are linked to anaemia
3.2 billion people at risk
2-500 million cases a year
1-2 million deaths per year- most are children under 5
Schistosomiasis
Blood fluke
Bilhartzia
Liver failure
1 billion people infected
Constantly laying fertilized eggs
Ascaris
Giant nematode
GI infection
Malnutrition
1 billion people infected
Ectoparasite – lives outside of host
Microparasites
Small
Multiply directly in host- 10^9/10^10 per host
Often cause transient infection- immune response that can clear out the parasite
Results in sterile immunity
Microparasites
, Large
Don’t multiply inside host
Cause chronic infection
Concomitant immunity
Concomitant immunity- the presence of the parasite within the host confers a degree f protection
against superinfection
Outcome is chronic infection and density dependent disease
Malaria has evolved and grown resistance to every malaria drug that has been developed
Why are parasites difficult to control?
Eukaryotic
Large and complex
Complex life cycles
Immune evasion
Eukaryotic
Parasites are eukaryotes
Have a similar structure and metabolism to the host species they infect
Chemotherapy is like cancer chemo
Need to look for unique pathways or structural differences in key molecules
Immunity also relies on identification of unique antigens- structural overlap with host proteins
makes this discrimination difficult
Failure to discriminate self and non-self may exacerbate damage by causing auto immunity
Large and complex
Parasites have thousands of different molecules
Finding a suitable target/ antigen it can be difficult
Macroparasites are physically large and cannot be removed by phagocytosis
Complex life cycles
Parasites often have complex life cycles involving ‘obligate’ passage through a mammalian host
and invertebrate vector
Within each host there are often several distinct life cycle stages, each of which are antigenically
and metabolically distinct
Phagocytosis
Binding via specific receptor subsets
Reactive NO/O metabolites
The plasma membrane derived vacuole is acidified by protein pump
Phagosome lysosome fusion occurs
Particle ingested and destroyed by acid proteases
Host immune response
Some parasites have become adapted to survival in macrophages. In doing this they perturb the
induction of the immune response
Immune evasion example 1
Giardia, malaria, trypanosoma bricei
These have evolved mechanisms of antigenic variation which prevent the host from developing
effective immunity and result in chronic invasion
immune evasion example 3
Toxoplasma gondii and trypanosoma cruzi
, Hide as dormant stages in immunoprivileged sites like muscle, eye or brain and avoid interaction
with the immune response
Adaption to parasitism
Amoeba- pond organism, moves in contact with substrate, hunter/ killer, phagocytic
Entamoeba- human pathogen
Naegleria- soil amoeba, opportunistic human parasite
Entamoeba histolytica
Human pathogen
Directly transmitted gut infection
Amoebic dysentery
Some species cause fatal liver disease
The parasite attacks the gut epithelium forcing its way through
the basement membrane, lysing cells as it progresses
Even macrophages and white blood cells trying to fight infection
are destroyed
In some cases parasite may escape from the gut and form
localised abscesses in the liver- this stage of infection can be
fatal
Entamoeba is adapted to colonise human gut tissue
Upregulated adhesion
Increased phagocytosis
Proteins associated with virulence have been identified
Naegleria
Facultative pathogen which can live for many generations without infecting host
Flagellate trophozoites are thought to enter through the nose during swimming in warm water
and thereafter the brain by locomotion
destruction of neurons causes primary amoebic meningoencephalitis
Adaptions to a parasitic lifestyle
Advantages of a parasitic lifestyle
Unlimited food
, Protection
Transportation
Challenges of a parasitic lifestyle
Immune evasion- must evolve mechanisms to get around immune system
Removal
Transmission- for it succeed it must get to other hosts
Removal blocked in Giardia by attachment
Evolved- concave surface acts as sucker to the animal host’s intestinal epithelial cells
Malaria parasite sequester in capillaries
Malaria parasites in red blood cells would be removed by the spleen
Release proteins to the surface of red blood cell, causing the parasite to adhere to the surface of
capillaries therefore not being removed by the spleen
Hookworms attach to the oesophageal muscles to intestine
Has jaw/ teeth that enables into remain attached to the intestine
Lice attach to hair
Immune evasion-trypanosomes
Have flagella enabling them to swim through the blood stream
They evolve quicker than the immune system can respond
They change their protein coat, changing a single protein, switching to different surface type so
the immune system cant recognise it
Transmission
Direct life cycle (direct transmission)
Indirect- intermediate hosts (vectors)
Direct life cycle
There is direct transmission from host to host
They can have an in-between stage where they are free living
Example of direct transmission of trichomonas
Inhabits urinogenital tract
Transmitted venereally
3.1% of American women and 13.3% of African American women
Aprox 6000 cases a year in UK
Direct transmission of entamoeba histolytica
Found in soil
Faeco-oral transmission
Cause of amoebic dysentery
Synchronising host and parasite life cycles
Sync there life style with their host
E.g. nematodirus battus- hatching delayed till warm spring when susceptible lambs start feeding
E.g. hook worm
Arreseted development in hookworms
1000 million people affected
Remain dormant in host through dry season
Migrate to intestine and mature during rainy season laying masses of eggs
Eggs in faecal mass hatch and larval development starts for new infection
Trichinella kills host
Passage by carnivorism- when the host is killed the meat is then eaten by another possible host
in order for them to passed on
