Paristology Flashcards
Parasite
An organism that lives and feeds on or in an organism of a different species and
causes harm to its host.
eukaryotic protozoan
singel celled
malaria
leishmania
toxoplasma
metazoan (helminth) endo-parasites.
roundowrms-nematodes
flatworms-cestode,trematode
Life cycle
single host simple
multiple host complezx
A definitive host is one in which the parasite reaches sexual maturity or in which
the parasite’s sexual reproduction occurs
intermediate host is one that is required for parasite development but one in
which the parasite does not reach sexual maturity
Immune evasion and immunomodulation
Protozoans are rapidly proliferating and small
hiding inside host cells and also by cycling the
proteins that might come into contact with immune cells
Malaria infects erythrocytes which lack MHC class I so avoid cytoxic T cells
Trypanosomes live extracellularly, constantly vary their surface glycoprotein, forms a dense coat to protect from immune recognition
Helminths are large, unable to hide or mutate quickly, use immunomodulation
export a range of immunomodulatory mediators, to dampen TH1 and TH2 proinflammatory responses
Strong and sustained Th1 responses lead to pathology
Strong and sustained Th2-type responses result in worm expulsion
can be used in therapy to reduce overactive inflammation
immunopathology
Not desired by parasite, wants to coexist with host not die
Usually due to overresponsive immune response
due to age, genetics exposure to other pathogens
Protozoan
categorised based on how they move
amoeboid movement
(using cytoplasmic protrusions),
ciliary movement (using hair-like projections),
flagellar movement (using beating flagella)
gliding motility (where parasite and host membrane
receptors interact and through the use of its actin-myosin motor the parasite glides along the
host cell surface).
Apicomplexans
Plasmodium, Toxoplasma,
All obligate intracellular parasites
Use plasma membrane to create vacuole to enter cell and avoid phagocytosis
evolved from plants
retained the apicoplast, a vestigial plastid organelle
site of fatty-acid synthesis.
apical complex
cytoskeletal structures and associated membrane-bound secretory organelles
Apicomplexans infection
deploy secretions from micronemes, rhoptries and dense granules through
its conoid structure
form a parasitophorous
vacuole (PV) that protects the parasite from acidification, lysosomal fusion and destruction.
Microneme secretions mediate gliding motility by the actin-myosin motor
Rhoptry secretions function in the formation of the PV and against host immunity.
Dense granule secretions mediate PV housekeeping and also contribute to immune defence.
Toxoplasma gondii and Toxoplasmosis
Life cycle
Cats and rodents/brids
Cat definitive host
male and female gametocytes will fuse in the cat’s intestine making oocytes expelled in faeces
oocytes sporulate and become infective, survive for long time until bird/rodent injests them.
rodent intermediate host-
oocyst wall disolves in gastrointesitnal tract, release parasite which enter intestinal wall to infect macrophages and other nucleated cell
reside in a parasitophorous vacuole and are called tachyzoites
Proliferate by asexual reproduction, lyse cells then reinfect
Tachyzoites cleared by Type 1 pro inflammatory response using IFN gamma, IL-12
Some parasites develop into bradyzoites, slow growing and form latent cysts, eaten by cat
Causes rodent to lose fear of cat so more likley to be eaten
Pathology of toxoplasmosis
Humans and other animals can get infected by either ingesting something contaminated with
cat faeces (oocysts) or by eating raw/undercooked meat (bradyzoite cysts)
parasites will convert to tachyzoites and cause acute infection.
Acute infection-flu like symptomps
In an immunocompromised patient can result in encephalitis, chorioretinitis or death.
tachyzoites can be transmitted transplacentally to a foetus,
stillbirth, congenital blindness and central nervous system damage
Big risk for sheep and marine animals due to waste water run off
Plasmodium and Malaria
a female Anopheles mosquito
Mosquito-definitive host
vertebrate-intermediate
In mosquito sexually reproduces,
In liver (parasite replicate asexually without causing symptoms)
The blood phase (where parasites replicate asexually and cause disease)
Sporozoites injected into host when mosquito bites human
Infect liver hepatocytes and form liver schizonts over 2 weeks
Schizont contains thousands of merozoites
Merozoites burst out and infect erythrocytes forming a trophozoite
Trophozoite forms schizont in rbc and releases more merozoite
schizogony- asexual replication
merozoite can also form gametes in RBC and are taken up by mosquito
Malaria
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
P. falciparum causes the most severe disease and is most widespread in sub-Saharan Africa,
thereby causing the most cases.
Can infect migratory birds and reptiles
CLimate change making plasmodium more permissive as mosquito spreads
Malaria pathology
liver phase is asymptomatic
blood stage is what causes malarial disease: muscle
ache/pain, nausea & vomiting, high fever
severe disease pathology includes anaemia, respiratory distress, renal failure, cerebral inflammation and death
An early and robust Th1 pro-inflammatory response
keeps parasite numbers in check until an antibody response capable of clearing residual parasites can develop. If the pro-inflammatory response is too intense or mis-timed it can
elicit immunopathology and malarial disease
Merozoites eat the globin chains of hemoglobin to get amino acids for reproduction
Haem parts are toxic and need to be polymerised into hemozoin
Malaria in mosquito
Mosquito takes up gametes in RBC
Micro and macrogametes fuse in midgut to form zygote
Form ookinete which moves to salivary gland and forms oocyst
Oocyst bursts releasing sporozoites into salivary glands
The infect humans, infect liver hepatocyte then erythrocyte then gamete and back to mosquito
Malaria relapse
Only vivax and ovale can cause relapse
Form liver hypnozoites
Have an extracyclic stage as when blood transferred from infected no relapse
Malaria symptomps
Fever, nausea
Mosquito can identify humans by heat, fever identifies infected human so can take up malaria gametes
Cyclic fever
Fever helps sync up when schizonts burst by slwoing down trophozoite maturation
This means if a schizont bursts, causes fever, other trophozoites slow down until the new ones catch up and eventually they synchronise
By synchronising fever occurs when most gametes released
Malaria immune evasion
Falciparum
Makes PfEMP1 and exports to surface of RBC
P. falciparum erythrocyte membrane protein 1 is a nodule like protein which can stick to each other and healthy RBC so clump together forming rosettes and bind endothelial receptors so sequester
This is done to avoid passing through the spleen and being cleared,
Due to sequestration at the brain and kidney harmful as can cause kidney failure, coma by trigerring inflammation at brain blocking blood vessels and breaking down blood brain barrier
Each round of replication makes new PfEMP1 so hard for immune system to keep up
Malria resistance
haemoglobinopathies like sickle cell or thalessimia
Sickle cell- low oxygen tension decreases malaria growth
Less PfEMP1 made, easier to clear RBC,
alpha thalessimia
Protection against anemia
Reduced rosettes and sequestration
Beta thalessimia
Easier to remove RBC
REduced groeht
Less rosettes and sequestration
Vivax uses duffyn antigen to recognise RBC
In west Africa Duffy-ve, immune
Malaria Treatment
Artemisinin- antimalria drug
Artemisinin combination therapies
Quinine-similar to chloroquine which malaria is resistant to
Kills parasite, meybe by acting on hemozoin
Vector control
Gene drive, mutate mosquitoes so infertile
Insectisides-resistance
REmove breeding ground like stagnant water
Biological controls-fish which eat larva
Bed nets-anapheles mosquitoes only bite at night
Give lots of people ivermectin which is toxic to malaria even if they dont have it
Testing
Rapid flow test
looks for plasmodium lactate dehydrogenase-all plasmodium
HRP-7 only falciprum
Parasite can evade tests, stopped expressing HRP-7
Leishmania
e flagellated promastigote and the non-motile
amastigote
All have kinetoplast, a dense DNA containing structure held within a single mitochondrion.
Infective metacyclic promastigotes are injected into vertebrate by sandfly bite
taken up by macrophages and lose their flagellum, forimg amastigote
replicate asexually, lysing and reinfecting cells
If a sandfly bites take up amastigotes they form procylic promastigotes ,then replicate asexually into metacyclic infectious promastiigote
No evidence of sexual reproduction
Leishmania LPG
Leishmania surface covered with Lipophosphoglycan LPG,
LPG binds a midgut galectin to anchor it to the sandlfy
LPG helps resist complement attack and ROS bursts
The type of LPG affects which sandfly is infected
P. papatasi can bind L. major–specific LPG only
Leishmania Pathology
Fever, skin sore
swelling of slpeen and lymph nodes
natural mammalian host for L. braziliensis is the two-toed sloth
Due to rainforest destruction as humans move in they also get infected
Can cause sever disease
Trematodes (flukes)
Schistosoma spp.
Schistosoma cercariae
Schistosoma cercariae
cercariae with taile
contacts people in the water, penetrates skin as head of larva has enzymes to melt skin
larval cercariae loses tail becoming schistosomulae and moves to portal blood to enter liver and mature
Adult male and female pair up with female inside canal of male
Mature worm migrate to venous plexus of bladder or mesenteric venule of rectum
Live for 5-10 years
Eggs shed in faeces or urine
Eggs hatch into miracidia which infect snails and form sporocysts
Release cercariae
Schistosomiaiasis
Pathology
Intestinal disease- hepato-splenomegaly
fibrosis and calcification of the liver
bladder fibrosis, calcification and cancer
Pathology due to eggs
Some eggs reflux instead of being shed into the liver/bladder, form granuloma,
High worm and egg burden cause many granuloma, initial TH1 response, TH2 response 9 weeks later causes fibrosis and calcification
Swimmers itch, itch when cercariae pass into skin
Schistosomiaiasis
Control
Elimate snails, biological control
HArd to kill all of them
Stop swimming, hard
Treat with Praziquantel
Even if no symptomps
Put boots on cows to stop infections in paddy fields
Hard to make vaccine
Poison water
