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96 Cards in this Set
- Front
- Back
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What are Protists?
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Unicellular eukaryotes
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Describe Apicomplexa
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5000 species
Mostly intracellular obligates Includes: Toxoplasma, Plasmodium and Cryptosporum |
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How many species are in the Toxoplasma genus?
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1 species
-->T. gondii |
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How is Toxoplasma gondii transmitted?
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Food and water borne
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What are the domain, kingdom, superphylum, phylum, class, order, family and genus of T. gondii?
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Domain: Eukaryota
Kingdom: Chromalveolata Superphylum: Alveolata Phylum: Apicomplexa\ Class: Coccidia Order: Eucoccidiorida Family: Sarcocystidae Genus: Toxoplasma |
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Where was T. gondii first described?
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In gundi (African rodent)
Also found in rabbits in Brazil at the same time |
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What is the standard basis for diagnostic test for T. gondii?
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Sabin and Feldman Serological dye test
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What is the definitive host for T. gondii?
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Feline species
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Describe Coccidia protozoan parasites?
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Eukaryote
Unicellular Intracellular hylum Apcomplexa Food and water borne pathogens Development of oocysts that are shed with the definitive host feces and contaminate the environment |
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What are some of the coccidian genuses?
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Toxoplas gondio
Eimeria sp. Sarcocystis sp Neospora sp Cryptosporidium |
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Describe the life cycle of T. gondii
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Sexual cycle in the cat
Oocysts/sporozoites released from the cat in its feces Contaminate other animals/ppl Tachyzoites enter cells where they replicate Can get activated Asexual cycle in humans/animals Inthe sexual cycle, tachyzoites can become bradyzoites which encyst |
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How does T. gondii usually cause contamination?
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Via the oral route
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What are the ways T. gondii can contaminate?
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1) Ingestion orf raw/partly cooked meat containing tissue cysts (bradyzoites)
2) Ingestion of oocyst-contaminated cat feces through hand-to-mouth contact 3) Drinking water contaminated with oocysts (sporozoites) 4) Transplacental infection in utero (tachyzoites) 5) Transplantation of an infected organ (bradyzoiets in tissue cysts) or blood transfusion (tachyzoites-rare) |
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What happens following ingestion of sporozoites (in oocysts) or bradyzoites (in tissue cysts)?
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The sporo/bradyzoites are freed from the cyst wall by digestive enzymes and invade the intestinal epitehlium
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What happens during the sexual cycle?
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Starts after feeding on an infected prey
Onccurs only in the intestinal epithelium of Felids Sporo/bradyzoites differentiate into gametes that produce oocysts Leads to oocyst shedding |
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Describe the asexual cycle
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Can take place in any warm-bloded vertebrate, inluding cats
Sporo/bradyzoites differentiate into the virulent tachyzoite state |
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How is infection disseminated?
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Disseminated by tachyzoites throughout the body of the host
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What happens after 1 week of infection?
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Immune response eliminates most tachyzoites
But some have reached immune privileged areas and differentiate into encysted bradyzoites, which are drug resistant and remain for the lifetime of the host |
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What are the best precursors to the sexual cycle in cats?
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Tissue cysts
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What kind of a pathogen is T. gondii?
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Major zoonotic pathogen
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Why is it a good zoonotic pathogen?
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Huge reservoir of intermediate hosts
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What is T. gondii's prevalence in humans?
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30% of human population is seroppositive
Up to 60% in Quebec, Nunavut, western Europe |
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What fdoes T. gondii prevalence in humans depend on?
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Mostly on nutritional habits (undercooked meat)
Also on contact with cats |
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What is the prevalence in animals?
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10% in pork
40% in sheep/lambs 20-63% in goats |
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Is toxoplasma usually benign or malignant?
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Benign
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When in Toxoplasma not benign?
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1) Immunocom[promised patients
2) If primary infection with T. gondii happens during pregnancy |
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What happens if a woman who is pregnant gets infected with T. gondii for the 1st time?
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Tachyzoites can cross the placenta
Can lead to miscarriage or intrauterine death |
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What happens if the woman is infected during the 1st trimester?
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incidence of transplacental infection is low, but disese in neonate is most severe
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What happens if a woman gets infected in her 3rd trimester?
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Incidence f transplacental infection is high, but infant is usually asymptomatic at birth
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What are the most vulnerable groups to toxoplasmosis?
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1) AIDS patients: symptomatic phase when CD4+ T cell count <200 cells/uL due to tissue cyst reactivation --> Toxoplasmic enephalitis (TE)
2) Allograft oran recipients: immunosuppressive therapy is necessary to tolerate the allograft, but high risks of tissue cyst reactivation 3) Pateins on prolonged corticosteroid therapy --> anti-inflam drug that suppresses inflam disorder 4) Fetus (incompetent immunological mechanisms): transplacental transmission of tachyzoites |
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Where does the asexual cycle of T. gondii take place?
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Intermediate hosts : humans, cattle, rodents, pigs, sheep, cats etc (warm-blooded vertebrates)
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What is the definitive host of T. gondii?
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Cats and other Felids through carnivorism/predation
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What are the developmental stages of T. gondii?
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Tachyzoites
Bradyzoites in tissue cysts Macro- and microgametes Sporozoiets in ocysts |
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Describe the tachyzoite stage.
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Acute/invasive/proliferative stage
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Where van T. gondii replicate as tachyzoites?
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Replicates intracellularly
Can replicate in ANY Nucleated cell |
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How long is the tachyzoite cyce?
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8 hrs
Can spread all over the body in a week |
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How does T. gondii invade a cell?
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Parasite glides along the surface until it finds a host cell
Then it glides in Uses its Apicomplexa to actively enter the cell (not just by phagocytosis) |
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What subcellular strutures does T. gondii have?
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Complete set of canonical euk organelles: nucleus, golgi etc
Plus 2 other organelles: mitochondrion, APICOPLAST |
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What kind of organelles are the mitochondrion, apicoplast?
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Endosymbiotic organelles
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What makes up the apical complex?
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Cytoskeletal elements
Secretory organelles (micronemes, rhoptries) |
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Where did the apicoplast come from?
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Algae
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What is the apicomplex important for?
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Choroid --> Internal part of the apicoplast, required for invasion
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What are the secreted organelles of the apicoplast?
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Rhoptries: club shaped organelles
Micronemes:secreted into PV Dense granules: Secrete ptn into vacuole during invasion These are required to help form the PV and to stay in it |
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How many mbs does toxoplasma have?
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3
-->Makes a fairly rigid structure |
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Describe how the parasite invades the host
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Mobile jct exists between the parasite and the host
when the parasite recognizes the host because of surface Ag, the parasite secretes Microneme and then Rhoptrie to help it get into the PV Then dense granules are secreted into the host cell |
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How does Toxoplasma replicate?
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Endodyogeny
2 daughtersw are assembled within the mother cell |
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At what stage is Toxoplasma in a bradyzoite form?
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Dormant/chronic stage
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Describe bradyzoites
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Morphologically similar to tachyzoites, but fctnally and physiologically distinct (have a different set of Surface Ag)
Granules of amylopectine (reserve carbohydrate) |
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Where do bradyzoites reside?
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In tissue cysts, which are derived from PV + cyst wall
10-200 um |
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Where is the dormant stage of this parasite found?
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Muscles (infective stage)
Brain Persists for the life time of the host |
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What is central to the pathogenesis of T gondii?
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Bradyzoite to tachyzoite interconversion
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What are bradyzoites resistant to?
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Low pH
Host digestive proteases (in the stomach) |
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Are tachyzoites resistant to low pH and host digestive proteases?
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No, hey are susceptible
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When to bradyzoites reactivate to tachyzoites?
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In immunosuppressed patients
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what is the form of toxoplasma in the sexual stage?
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Sporozoite/oocyst
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Describe the oocyst
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Oval
13 um in size Resistant stage Viable in moist soil -- 18 months |
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How are oocysts made?
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Product of the sexual cycle (micro and macrogametes)
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How are oocysts passed out of the cat?
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Passed out in the feces 10-14 days after infection
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In what animal does the sexual cycle take place?
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Cats
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How many sporozites does each sporulated oocyst contain?
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8 (~5 days)
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Who can this parasite infect?
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Humans and other herbivores
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Why are coccidian oocysts a problem?
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They are the spore stage of certain protists
Oocyst wall is essential to survival Wall makes oocysts very resistant to dessication and chemical disinfection Oocysts can survive for lengthy periods outside a host |
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What can oocysts esist/.
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Physical agents: UV, dessication, freezing
Chemical agents: Ozone, bleach, iodine, ethanol, formalin, salts |
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How long can oocysts persist in soil?
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18 months
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How long can it persis in water?
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54 months
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Describe the oocyst right after it is excreted
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Unsporulated
Non-infectious Contains a single, undifferentiated cytoplasmic mass Zygote stage of the parasite surrounded by a protective wall |
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When does sporulation occur?
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At appropriate T and humidity
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What happens in sporulation?
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Occurs by meiotic division
Cytoplasm divides ubti a cgaracterustuc number of submasses (secondary sporoblasts) These develop a resistant wall and are termeed sporocysts Infectious stages (sporozoites) are formed within the sporocysts (this is how the sporozoites are protected by the the oocyst/sporocyst |
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How many sporozoites are in each sporocyst?
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4
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In what animals is the oocyst of T. gondii infectious?
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Basically all warm-blooded vertebrate
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When do oocysts become infectious?
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1-2 days after being shed by cats, after sporulation
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How many cats shed oocysts at any one given time?
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~2%
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Can oocyst shedding occur, even after repeated exposure to the parasite?
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No
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Can you get a direct infection from handling cats?
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Very rare
But oocysts can be found on the fur of cats, usually not in infectious form |
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What is one way T. gondii oocysts can be transmitted?
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Water-borne transmission
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How does the host control this parasite infection?
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Humoral and CMI response
Th1 response is required for host reesistance |
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What are the effector cells during the acute and chronic phases of toxoplasmosis?
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CD8+ T cells are major effectors
CD4+ T cell are required for regulation of the IR |
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what are the 1st line of defense?
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Macs
NK cells |
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Which cytokine is required for the induction of an efficient Th1 response?
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IL-12
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Which cells produce IL-12?
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DCs mainly
Also Macs, and neutrophils |
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What is the major effector cytokine? And what does it do?
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IFN-y
Activates hematopoietic and non-hematopoietic effector cells restricts intracellular parasite growth Can kill intracellular parasites |
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What are some secondary effectors that are important in controlling this parasite?
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Reactive O2 and N2 species (IFN-y dependent)
Tryptophan starvation (IFN-y dependent) p47 GTPases (IFN-y dependent) TNF-a, IL-6, IL-1: work in synergy |
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How can acute infection be assessed clinically?
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By serology, looking at IgG and IgM
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When do IgG Ab start to appear vs the parasite?
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1-2 weeks after infection
Reaches its peak after 6-8 weeks Gradually declines after 1-2 years |
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Does the Ab titer relate to the severity of the illness?
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No
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What is a commonly used test to detect T. gondii in the blood?
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ELISA
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What test can be used for intra-uterine and cerebral disease?
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PCR (detection og parasite DNA in fluids an exudates)
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How can one prevent toxoplasmosis?
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Avoid eating undercooked meat
Wash fruits and vegetables thoroughly Avoid soil contact Avoid drinking untreated water Empty the litterbox daily |
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What are treatments for acute toxoplasmosis?
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Pyrimethamine
Sulfadiazine Clindamycin Spiramycin |
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What does pyrimethamine do?
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Interfers with folic acid synthesis
Inhibits the enz DHFR antimalarial medication |
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What does sulfadiazine do?
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Sulfonamide antibiotic (Folic acid synthesis) used in combo with pyrimethamine
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What is clindamycin?
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Lincosamide antibiotic amide
Used mostly for ppl with HIV/AIDS Interferes with ptn synthesis |
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What is spiramycin?
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Macrolid antibiotic used for pregnant women
Interferes with ptn synthesis |
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What is used for chronic toxoplasmosis?
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Nothing yet, but in mouse model:
Atovaquone, clindamycin |
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Why is toxoplasma so successful?
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-Intracellular parasite: protected from manmy immune effector mechanisms
-Can infect any nucleated cell -chronic infection in any immune privileged areas -Intracellular niche resistant to fusion with the host cell lysosomes, which degrafe phagocytetosed organisms -Manipulated host cvell processes and host immune effectors (downregulates Ag presentation, upreg'l anti-inflam, use host cells to disseminate cross BBB) |
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Are hosts often killed?
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No
Balanced host-parasite interaction Required for parasite survival, persistence and transmission |
