Protozoans and the diseases they cause Flashcards
a) How are protozoans categorised
b) characteristics of apicocomplexans (+ examples)
a) by how they move. Can use amoeboid movements (using cytoplasmic protusions), ciliary movent (using hair-like projections) flagellar movement (using beating flagella) or gliding motility (parasite and host membrane receptors interact, actin-myosin motor allows parasite to glide across host cell surface)
b) Have evolved from plants and retain the apicoplast (vestigal plastid organelle essential for parasite lipid metabolism and site of fatty acid synthesis). Have an apical complex (group of cytoskeletal structures and associated membrane-bound organelles). Parasites deploy secretions from micronemes, rhoptries and dense granules through the conoid structure to mediate active invasion of host cell and form a parasitophorus vacuole (PV) that protects parasite from acidification, lysosomal fusion and destruction. Microneme secretions mediate gliding motility. Rhoptry secretions function in formation of PV and against host immunity. Dense granule secretions mediate PV upkeep and immune defence.
Plasmodium, Toxoplasma, Theileria, Babesia, Cryptosporidium
Toxoplasma gondii lifecycle
Obligate intracellular parasite, normally cycling between cats and their prey (rodents, small birds).
1) Male and female gametocytes fuse in cat’s intestine (cat is definitive host) and produces oocytes, which are expelled in faeces
2) Oocytes will sporulate and become infective. Can survive and remain infective for a very long time, until they’re ingested by a rodent/bird (intermediate host)
3) Oocyte dissolves in GI tract, released parasites penetrate intestinal wall and infect macrophages
4) Inside cells, they reside in parasitophorus vacuoles and are called tachuzoites. They rapidly proliferate through asexual reproduction, lysing and reinfecting cells (destructive for tissues)
5) A Type 1 pro-inflammatory response (mediated by IL-12, IFN-γ and innate immune cells) control and eventually resolbe this phase of infection
6) Tachyzoites are cleared, but host defences stimulate some parasites to morph into bradzoites (second asexual stage of parasite development). They are slow growing and organise into tissue cysts and remain latent. They are resistant to drug treatment at this stage.
7) When a cat eats an infected animal parasites are reactivated and cycle continues
Pathology of toxoplasmosis
Humans and other animals can be infected either by ingesting something contaminated with cat faeces (ingesting oocytes), or by eating raw/undercooked meat (ingesting bradyzoite cysts). Parasite convert to tachyzoites and cause acute infection. In healthy individuals, will have mild flu-like symptoms and is not life threatening. In immunocompromised patient infection can be devestating, potentially resulting in encephalitis, choriorentinitis or death. Toxoplasma tachyzoites can also be transmitted transplacentally to a foetus. In humans can cause stillbirth, congenital blindness and CNS damage. Transplacental transmission is a big risk in sheep and can lead to spontaneous abortion, foetal mummification and severe congenital defects (so spread must be actively limited during lambing season). Wastewater runoff into coastal areas and rising sea temp means oocysts survive longer, meaning there is an increase in Toxoplasma affecting marine animals.
Plasmodium lifecycle
Indirect lifecyle (2 hosts). Transmitted through the bite of a female Anopheles mosquito and has 3 stages of development, one in mosquito (definitive host) and two in vertebrate (intermediate host): Mosquito phase (sexual reproduction occurs), liver phase (asexual replication without symptoms), blood phase (asexual replication causing disease).
Sporozoites injected into vertebrate during blood meal. Go to liver, infect hepatocytes, develop to liver schizonts over 2 weeks. Mature liver schizont contains thousands of merozoites that burts out and infect erythrocytes, starting blood phase. Each merozoite develops to a trophozoite, then into a schizont that then releases new meozootes (through asexual replication - schozogony) that reinfect new erythrocytes.
a) five Plasmodium species that cause disease (and most common)
b) effect of bird migration and climate change
a) P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi - P. falciparum causes most severe disease and is most widespread in sub-Saharan Africa
b) Plasmodium can also infect birds and replites, so migrating birds carry parasite north. Anopheles mosquito vector exists everywhere, so parasite can be transmitted to local populations. Climate change and global warming are making regions usually free from Plasmodium permissive to its transmission and survival.
Pathology of Plasmodium and susceptibility to disease
Liver phase is asymptomatic. Blood stage causes malarial disease: muscle ache/pain, nausea, vomiting, fever. In sever pathology: anaemia, respiratory distress, renal failure, cerebral inflammation, death.
Overcoming disease requires a timely and balanced response. An early and robust Th1 pro-inflammatory response keeps parasite numbers in check until an antibody response can develop to clear residual parasites. Of pro-inflammatory response is too intense or mis-timed it can ellicit immunopathology and malarial disease
Many factors can influence severity of disease (previous exposure, age, genetics). Up until 6 months old, infants are protected by residual circulating maternal antibodies. After they disappear, there is a high susceptibility stage that spans early childhood and risk of severe disease. After repeated exposures, eventually there will be reduced disease severity and ultimately clinical immunity (parasite infects but patient is asymptomatic)
Immune evasion of P. falciparum
Exports parasite proteins onto outer membrane of RBCs (PfEMP1, a protein encoded by a set of 60 var genes). Var genes are located in subtelomeric regions of the parasite’s 14 chromosomes, areas that are highly susceptible to recombination. Each replication round gives rise to new PfEMP1 variants, so any parasite may have a unique set of var genes. This is difficult for immune system to keep up with, so may take many exposures to develop a wide enough antibody repertoire to effectively control parasitaemia.
PfEMP1 also binds endothelial receptors, allowing parasitised erythrocytes to sequester and avoid clearance by the spleen. Th1 response when a schizont bursts causes an upregulation of these receptors and promotes further sequestration. Parasitised erythrocytes also stick to eachother and to healthy RBCs, forming clumps (rosettes), which can lead to blockage of blood vessels in the brain and breakdown of BBB. This inderlies neurological symptoms.
Natural resistance to malarial disease
Natural resistance appeards as selection for haemoglobinopathies such as haemoglobin sickle cell anaemia allele (HbS), α and β thalassemias. Haemoglobin disorders affect critical balances in water potential and solute conc, so parasite growth is impaired, expression of PfEMP1 is lower, so severe disease less likely.
Leishmania structure and lifecycle
Parasite exists in two forms: the flagellated promastigote and the non-motile amastigote. They are characterised by the presence of a kinetoplast, a dense DNA-containing structure held within a single mitochondrion.
Have an indirect lifecycle. Does not involve sexual reproduction during any stage of its lifecycle, there are no definitive hosts, just intermediate. The cycle is characterised by the conversion of the parasite from promastigotes to amastigotes in the vertebrate host, and vice versa in the sandfly vector. Infective metacyclic promastigotes are injected into vertebrate host through a sandfly bite. Taken up by macrophages and lose flagellum (become amastigotes). They replicate asexually, lysing and reinfecting cells. If a sandfly takes up amastigotes during a blood meal, parasites develop back into procyclic promastigotes, replicate asexually again and then turn into infective metacyclic promastigotes.
Leishmania defence from immune system
Surface of parasite is covered in the carbohydrate LPG. LPG maintains the parasite in the sandfly midgut and protects it from immune attack in the vertebrate host. LPG can be detected by TLR2, but to suppress the induction pathway (eg production of IL-12), Leishmania recruits cytokine supressors that negatively regulate TLR2 induction and impairs TLR2-mediated IL-12 release. LPG also has a section that is able to change length and complexity as the parasite divides and develops, enabling it to resist complement attack and withstand oxidative bursts within the macrophage.
The nature of the LPG determines which sandflies the parasite can infect, hence certain species are restricted to certain areas of the globe. However rainforest destruction and climate change means that strains previously restricted to certain areas are now integrating into new environments and human populations. Eg. L. braziliensis has a natural host of the two-toed sloth, normally living deep in rainforests away from humans, with the parasite existing in an ecological niche. Rainforest destruction means the sloths and sand fly vector are now coming in contact with humans adn their companion animals
Leishmania pathogenesis
Leishmaniasis can present in a variety of ways, and pathology depends on the parasite species, type of cell infected, host genetics and immunological memory. Most commonly seen in humans and dogs. Cutaneous, diffuse cutaneuous and mucocutaneous disease can occur, as well as the most sever form of infection being visceral disease, causing chronic fever, reticuloendothelial hyperplasia (causing spleen enlargement) and liver enlargement (causing liver failure and death)
