Term
| What is the definition of parasitism? |
|
Definition
| The state of living on or at the expense of another organism |
|
|
Term
| What is the difference between a parasitoid and a parasite? |
|
Definition
| A parasitoid always kills |
|
|
Term
|
Definition
| direct trophic interaction, which is beneficial to both organisms |
|
|
Term
|
Definition
| beneficial to commensal, neutral to host, indirect interaction |
|
|
Term
| Does Giardia lamblia have the TCA cycle? |
|
Definition
|
|
Term
| Do schistosoma species have the TCA cycle? |
|
Definition
| They have the enzymes, but do not normally completly catabolise glucose |
|
|
Term
| Do trypanosoma have the TCA cycle? |
|
Definition
| Yes, but they switch off the mitochondria as soon as they enter the bloodstream |
|
|
Term
| What happens to the genome of an organism when it becomes a parasite? |
|
Definition
| it is reduced in size and complexity |
|
|
Term
| Why is their an evolutionary ratchet in becoming a parasite? |
|
Definition
| Many specializations and gene losses are needed, and it is difficult to reaquire gene function |
|
|
Term
| What additional options do parasites have for speciation? |
|
Definition
Classic allopatric speciation where parasite and host speciate together.
Parasite speciation but not host.
Host may speciate but not parasite. |
|
|
Term
| What normally occurs with zoonotic infections? |
|
Definition
| They are hypervirulent, or not harmful at all |
|
|
Term
| What is the red queen hypothesis? |
|
Definition
| "All the running you can do to stay in the same place" - host and parasite must keep evolving to maintain fitness relative to each other |
|
|
Term
| Which parasites are multicellular? |
|
Definition
Trematodes (flukes)
Tapeworms (cestoda)
nematodes - filaria, roundworms, whipworms, hookworms |
|
|
Term
| How is Giardia transmitted? |
|
Definition
| Contaminated food and water |
|
|
Term
|
Definition
| Diarrhea and abdominal pain |
|
|
Term
| How is Leishmania transmitted? |
|
Definition
|
|
Term
| Paragonimus westermani - What is it, and what is its life cycle? |
|
Definition
A lung fluke, causes inflammation and bleeding in lungs
Life cycle - Unembryonated eggs in water
Eggs become embryonated in water
Miracidia hatch and penetrate snail
Mature into sporocysts, rediae and cercariae in snail
Carcariae invade a crustacean
Migrate into metacercariae
Humans ingest inadequately cooked crustaceans
Metacercariae encyst themselves in the duodenum
Adults in cystic cavities in lungs lay eggs, which are excreted in sputum, or swallowed and passed in stool |
|
|
Term
| What is a direct life cycle for parasites? |
|
Definition
| Only living in one host for whole life cycle. Indirect requires multiple |
|
|
Term
| What is the hypothesized evolutionary model of trematodes? |
|
Definition
1. Free-living platyhelminths (before vertebrate evolution) - egg, larval and adult stages
2. Invasion into molluscs (primary parasitic event) - primary parasitic/micropredatory event - originally scavenging bacteria growing on mantle?
3. Development of larvae in tissues, emerging as free-living adult - cf. parasitoid wasps
4. Adults preyed on by vertebrates - evolutionary pressure to survive passing through intestine?
5. Established in vertebrate intestine (originally fish) - second parasitic event - essentially all digenea are parasites of gut- second parasitic event - essentially all digenea are parasites of gut
6. Elaboration/diversification of basic lifecycle |
|
|
Term
| What are the four most common methods for surviving in the host? |
|
Definition
mimicry (making coats or proteins that look like host)
immuno-suppression (secretion of cytokine-like molecules)
hiding away (e.g. in tissues with little protection or inside other cells)
keeping one step ahead (e.g. by constantly switching identity of surface proteins) |
|
|
Term
| What is the cuticle for and what is it made of? |
|
Definition
| In free living nematodes - environmental resistance, in parasites it is made of glycoproteins/glycolipids and is often immunogenic |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Which parasite is asymptomatic in 90% of cases? |
|
Definition
|
|
Term
| What can ascaris lumbricoides cause? |
|
Definition
| Eosinophilia, pneumonitis, malnutrition, small bowel and biliary tract obstructions, pancreatitis, liver abscess |
|
|
Term
| What is another name for Necator Americanus? |
|
Definition
|
|
Term
| Which clade of the platyhelminths are parasitic? |
|
Definition
|
|
Term
|
Definition
| A protective layer on platyhelminths that absorbs nutrients and secretes glycocalyx |
|
|
Term
| What is the general life cycle of flukes? |
|
Definition
Eggs pass into environment via urine/feces
Eggs hatch into miracidia
Miracidia penetrate snail
Reproduce asexually, forming cercariae
Cercariase escape host then either
Penetrate human skin OR
Settle on plants and become metacercariae OR
Penetrate fish, molluscs or crustaceans and become metacercariae
If the second two options, they must then be ingested while undercooked
Develop into adults in humans |
|
|
Term
| Schistosomiasis life cycle? |
|
Definition
Eggs released in feces or urine
Hatch, releasing miracidia
Infect snail
Sporocysts produced in snail
Cercariae released free living into water
Penetrate human skin
Lose tails during penetration, becoming schistosomulae
Enter bloodstream
Migrate to live and mature into adults
Migrate to venules of bowel/rectum and mate |
|
|
Term
| How do cestodes absorb nutrients? |
|
Definition
|
|
Term
| Cestode generalised lifecycle? |
|
Definition
Eggs released into the environment in feces
Secondary Hosts consume eggs in contaminated food
Eggs hatch into larvae which penetrate intestinal wall and migrate
Larvae develops into a cysticercus in muscle
Human eats contaminated meat
Cysticercus excysts to become a scolex that attaches to the intestinal walls and matures
Adult worms form new proglottids |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is echinococcus granulosis, and what disease does it cause? |
|
Definition
| Canine tapeworm, hydatid disease |
|
|
Term
| how do helminths modulate immune response? |
|
Definition
| They release cytokines and cytokine mimics, which increase the Th2 response, causing less inflammation, but also less toxicity to the parasite. They also release host like glycans, protease inhibitors which block signalling cascades and anti-oxidants, which block cytotoxic killing |
|
|
Term
| How are schistosoma eggs expelled? |
|
Definition
| They recruit Th2 cells, which form a granuloma around them to prevent a constant inflammatory response. The granuloma is pushed across the intestinal wall, allowing it to be excreted/ urinated out |
|
|
Term
| What bystander effects can occur due to helminth immunomodulation? |
|
Definition
Reduced vaccine efficacy, increased susceptibility to infection
reduced incidences of inflammatory disease, reduced tumour resistance, reduced autoimmune diseases |
|
|
Term
|
Definition
| Non-trophic symbiotic interactions - e.g. one organism carries another |
|
|
Term
|
Definition
| Bees bite through stem to reach nectar |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| How big is caenorhabditis? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What are the major protozoan pathogens of humans? |
|
Definition
| Plasmodium, toxoplasma, leishmania, trypanosomes (african and american) , giardia, trichomonas, entamoeba |
|
|
Term
| What are the advantages and disadvantages of small parasites? |
|
Definition
| Can hide in cells, but can be difested, able to move more freely, have higher populations for a lower energy cost, and are less likely to be parasitised themselves |
|
|
Term
| What are the apicomplexa? |
|
Definition
| an exlusively parasitic group, with an apical complex that helps them specialise in invasion |
|
|
Term
| What are the 5 main species of malaria? |
|
Definition
Plasmodium falciparum (most common)
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae (dangerous)
Plasmodium knowlesi ( zoonosis from macaques) |
|
|
Term
| What is the simple plasmodium life cycle? |
|
Definition
Sporozoites injected in saliva into humans
Migrate to liver
Undergo schizogony
Merozoites released from liver and enter blood cells
Undergo schizogony again
Go through asexual cycle in bloodstream, or are taken up again by mosquito |
|
|
Term
| What do sporozoites target? |
|
Definition
|
|
Term
| Which hepatocyte proteoglycans are recognised by sporozoites? |
|
Definition
|
|
Term
| What is the circium sporozoite protein? |
|
Definition
An abundant protein n sporozoites
Anchored to surface by GPI
Has a Thrombospondin type 1 (TSR) region, which is a domain involved in cell adhesion
Conserved across plasmodium
Interacts with proteoglycans on liver cells
It is proteolytically cleaved in region 1 by cysteine
This occurs when the parasites contact liver cells, and triggers cell invasion |
|
|
Term
| What does the erythrocyte cycle cause and when does it cause it? |
|
Definition
| fever, when the red blood cells are lysed |
|
|
Term
| What is gametocytogenesis? |
|
Definition
| An alternative to asexual replication, it occurs in the mosquito gut, and produces the infective malaria stage, nuclear replication occurs 3 times, and 8 microgametes are formed, triggered by xanthuric acid, lower Co2 levels and temperature, and higher pH |
|
|
Term
| What is sporogony and when does it occur? |
|
Definition
In the mosquito, it is a fusion of micro and macro gametes, turns zygotes into ookinetes that transverse the mosquito gut epithelium, turn into an oocyst between epithelium and basal lamina
oocyst bursts, releasing sporozoites
sporozoites migrate through haemocoel
invade salivary glands ready for transmission to new host |
|
|
Term
| What causes cryptosporidium, how is it transmitted, and what are the symptoms? |
|
Definition
Caused by Cryptosporidium parvum and Cryptosporidium hominus.
Transmitted through contact with contaminated water
Usually causes mild diarrhea that is self resolving
Immune deficient people may develop more serious injury |
|
|
Term
| What occurs during infection by toxoplasma gondii? |
|
Definition
Ingested cyst or oocyte (cat, bird or rat)
Cyst releases sporozoites that diferentiate into tachyzoites and invade tissue
If in bird or rat, bradyzoites invade epithelial cells before differentiating back into tachyzoites, invade any cells, and multiply before lysing the cells
They then form cysts in the brain, liver and muscles
If in cat, differentiate into tachyzoites and gametocytes
Gametocytes form zygote that matures into oocyst
Oocyst released in fetus
Disease in humans caused by zoonosis
Alter behaviour of hosts to increase transmission rate by impairing motor performance and increasing risk taking
Probably wont show symptoms in humans unless immune compromised |
|
|
Term
| Which parasites are kinetoplastids? |
|
Definition
| Leishmanias and trypanosomes? |
|
|
Term
| What is another name for african trypanomiasis? |
|
Definition
|
|
Term
| How are trypansomes spread? |
|
Definition
|
|
Term
| Are trypanosomes extracellular or intracellular? |
|
Definition
|
|
Term
| What does T. brucei infect? |
|
Definition
|
|
Term
| How is T. rhodesiense different from brucei? |
|
Definition
| It effects humans as well, kills in weeks/months, zoonosis disease |
|
|
Term
| Which trypanosome specialises in human infection? |
|
Definition
|
|
Term
| What is the disease progression for trypanosome infection (symptoms)? |
|
Definition
Early stage (stage I) Parasites in tissue fluids surrounding the fly bite site, enter bloodstream. Parasites proliferate in circulation in bloodstream and tissue fluids.
Fever, severe headache, muscle pain
As disease progresses in lymph and blood, symptoms include:
anaemia due to autoagglutination of RBC
cardiovascular, endocrine and kidney disorders
Late stage (stage II) Parasites invade central nervous system (CNS). Parasites sequestered in capillaries around the brain, from where they cross the blood-brain barrier
Invasion of the CNS and resultant inflammation
Sleep disturbances, alteration of mental state
Altered gait and reflexes, neurological and motor changes, lethargy, coma and death |
|
|
Term
| What is the chagas life cycle? |
|
Definition
Blood meal taken by hematophagous bug
Trypomastigotes injected
Transform into amastigotes
Multiply by binary fission
Transform back to trypomastigotes, burst out of cell into blood stream
Taken up by bug
Turn into epimastigotes
Multiply in midgut |
|
|
Term
| What are the symptoms of chagas? |
|
Definition
Acute phase
2 – 8 weeks
Fever, hepatosplenomegaly
10% mortality
Chronic phase
Cardiomyopathy
Heart arrhythmia and blocks
Heart enlargement (cardiomegaly)
Apical aneurism
Nerve degeneration, megaesophagus, megacolon |
|
|
Term
| How is Leishmaniasis transmitted? |
|
Definition
|
|
Term
| What is the Leishmaniasis life cycle? |
|
Definition
Sandfly takes blood meal and injects promastigotes
Promastigotes phagocytised
Promastigotes transform into amastigotes inside macrophages
Multiply then lyse cells
Sand fly takes a blood meal, takes up macrophages containing amastigotes
Amastigotes transform to promastigotes stage in midgut then divide
Migrate to proboscis |
|
|
Term
| What are the symptoms of the different types of leishmaniasis? |
|
Definition
Cutaneous leishmaniasis
L. major & L. tropica: Skin ulcers at the site of bite, with varied number of amastigote forms in it. Ulcers can heal or complicate.
Mucocutaneous leishmaniasis
L. braziliensis & L. mexicana: Ulcers of the skin, mouth and nose. South and Central America up to Texas, US.
Viceral leishmaniasis or Kala-azar
L. donovani: Fever, progressing to anaemia, wasting, enlarged liver and spleen, bleeding, and breathing difficulty. Death within 6-12 months. |
|
|
Term
| What is the general idea behind antigenic variation? |
|
Definition
Acquired immunity depends on antibody antigen interaction
Changing antigens prevents this, and stands in the way of vaccination |
|
|
Term
| How does T. brucei protect itself from the immune system? |
|
Definition
T. brucei is covered in variant surface glycoprotein (VSG), a homodimer that is anchored to the surface by glycosyl pphosphatidyl inositol (GPI). VSG proteins form a highly immunogenic monolayer over the trypanosome.
This VSG coat is periodically changed to produce a change in the immunological identity
This protects from innate immunity
Sugar fills the spaces in between the VSGs |
|
|
Term
| How is the T. brucei genome organised? |
|
Definition
| T. brucei has 3 classes of chromosomes, megabases, which are 1-6 mb, diploid and contain the housekeeping genes, intermediate size, and minichromosomes, which contain the library of antigenic variation genes |
|
|
Term
| Where is the active VSG gene? |
|
Definition
| In the subtelomeric expression sites |
|
|
Term
| Where are VSGs transcripted? |
|
Definition
| The bloodstream expression site (BES): these are dedicated telomeric polycistronic transcription units. |
|
|
Term
| Which two ways can T. brucei switch its antigens, and which is more common? |
|
Definition
Transcriptional switching, activation of a different BES - access to around 20 VSG genes
Recombinative switching - change of VSG gene in the active ES - access to 3000 VSG genes
Recombinative much more frequent |
|
|
Term
| how do Giardia undergo antigenic variation? |
|
Definition
by the continuous switching of VSPs
VSPs form a thick coat over cell body, flagella, ventral disk.
200-300 VSP genes, only 1 expressed.
Switching occurs ~1:10 generations.
Switching in the absence of immune pressure.
Switching is random |
|
|
Term
| How does plasmodium undergo antigenic variation? |
|
Definition
via PfEMP1 - plasmodium falciparum erythrocyte membrane protein 1
It, along with other proteins, form knobs on the surface of infected red blood cells
PfEMP1 has a TM domain and duffy binding like domains
PfEMP1 causes RBCs to rosett, or bind together with the infected cell in the middle, to avoid the immune system
PfEMP1 is routed to the plasma membrane through the cells secretory pathway
Being on the surface puts it into contact with the immune system
It is encoded by var genes
There are approximately 60
Var switching is mediated at the level of transcription
Var introns act as silencing elements
Repeat sequences near var genes causes them to cluster together, which may increase long term recombination and diversity
Maurers clefts are created on the surface of the erythrocyte to allow PfEMP1 to be secreted
Serial expression of immunologically distinct types allows proteins that go on the erythrocyte surface such as
Everything that needs to be changed is kept in one exon, everything that needs to be conserved is in a second |
|
|
Term
| Where are Var genes found? |
|
Definition
|
|
Term
| What is the allelic exclusion model and where is it found? |
|
Definition
transcriptional permissive location in nucleus that can only be occupied by one allele
In plasmodium |
|
|
Term
| What is RIFIN encoded by? |
|
Definition
| rif (repetitive interspersed family? |
|
|
Term
| What does STEVOR stand for? |
|
Definition
| Subtelomeric Variant Open Reading Frame - function unknown |
|
|
Term
|
Definition
| Chagas disease, cysticercosis, toxocariasis, toxoplasmosis, and trichomoniasis. |
|
|
Term
| Why has prevention of trypanosomiasis been unsuccesful? |
|
Definition
| because the established methods of vector control, trapping of flies and release of sterile males, work in principle but face significant logistical and financial difficulties Also, ntigen-targeting vaccine development is prevented by the variable surface glycoprotein (VSG) coat of the bloodstream form which allows the parasite to avoid the antibody-mediated immune response. Drug treatment of trypanosomiasis is difficult because available drugs are often toxic and resistance to them is increasing. |
|
|
Term
| Why do humans have an innate resistance to some trypanosomes? |
|
Definition
| Normal human serum (NHS) contains a trypanolytic factor (TLF), made of High density lipoproteins (HDLs), specifically TLF1 and TLF2. |
|
|
Term
| What is required for the lytic activity of NHS? |
|
Definition
| Endocytosis and trafficking of TLF to the low pH of the lysosome |
|
|
Term
| How does Leishmaniasis increase interaction with host immune cells? |
|
Definition
| At the bite site, vasodilaters improve blood flow to the wound, and the sand fly also transmits viruses and bacteria - this improves recruitment of neutrophils |
|
|
Term
| How does Leishmania enter cells? |
|
Definition
| It is taken up by phagocytosis, and resists the low pH and hydrolases? |
|
|
Term
| What does Leishmania effect inside the phagocytes? |
|
Definition
|
|
Term
| How do apicomplexan parasites survive inside cells? |
|
Definition
| They seem to induce the formation of a non-fusogenic vacuole, which is not acidified and is disconnected from host vesicular trafficking pathways. How this is achieved is still not fully understoodseem to induce the formation of a non-fusogenic vacuole, which is not acidified and is disconnected from host vesicular trafficking pathways. How this is achieved is still not fully understood |
|
|
Term
| How does T. cruzi stimulate uptake? |
|
Definition
via Ca2+ signalling
First they wound the cell slightly, before secreting Ca2+ through the gap
This signals lysosomes to the wound
The parasites then secrete ASM, causing ceramide generation
The cell membrane invaginates around the parasite, eventually creating a parasitophorous vacuole around the parasite
It then secretes TcTox, which creates pores, before escaping into the cytoplasm, and differentiating into amastigote |
|
|
Term
|
Definition
| Apicomplexan organelles (Apical organelles), during cell invasion they discharge membraneous and proteinacious material that contributes to the formation of a vacuole |
|
|
Term
|
Definition
| Apicomplexan secretory organelles that store adhesins. Secretion is regulated through a Ca2+ mediated pathway in response to cell-cell contact, ensuring polarised attachment, and possible limiting antibody recognition |
|
|
Term
|
Definition
an invasion motor
It requires a transmembrane link between the parasite cytoskeleton and host cell
Adhesins bind to receptors on host cell
Intracellular portions of adhesins are linked to short, dynamic actin filaments
Actin filaments and adhesin are propelled by myosin attached to an inner membrane complex
Myosin consumes ATP to move along the filament
Associated with the movement of actin filaments is a polarised dissassembly of actin filaments
Adhesins will be pulled through te plasma membrane
The entire complex is then disengaged with parasite proteases |
|
|
Term
| What happens as the glideosome pulls the parasite into the cell? |
|
Definition
|
|
Term
|
Definition
| A plasmodium feeding structure, used to digest host haemoglobin |
|
|
Term
| What is calpain and calpastatin? |
|
Definition
| Calpain is a regulatory protease that modifies cytoskeletons. Calpastatin inhibits it. |
|
|
Term
| How is calpain activated, and what does plasmodium use it for? |
|
Definition
| It is at the end of a G protein coupled receptor signalling cascade, and egress (breaking out of the cell) |
|
|
Term
|
Definition
| rosetting, uninfected red blood cells crowding around the infected one and masking it, or cytoadherence to the blood vessel wall, preventing the erythrocyte travelling to the spleen |
|
|
Term
| What is the greatest mortality group from malaria? |
|
Definition
| Cerebral malaria in children |
|
|
Term
| How does T. gondii modulate the host cell? |
|
Definition
| by translocating multiple effector proteins both across the plasma membrane of the host cell and across the PV membrane into the host cell cytosol. Several of these effectors have been identified as master regulators of the innate immune response, and the majority (known as rhoptry proteins (ROPs)) are injected into the host cell cytosol during invasion. |
|
|
Term
|
Definition
| activates signal transducer and activator of transcription (STAT) transcription factors |
|
|
Term
| What do ROP18 and ROP5 do? |
|
Definition
| They are involved in protecting the vacuole from the host innate immune system by preventing IRG recruitment to the PV surface. |
|
|
Term
| Once inside the cell, what effectirs does T. gondii secrete, and what do they do? |
|
Definition
| Dense-granule (GRA) proteins, into the host cell cytosol. GRA15 was shown to initiate NF-κB signalling (FIG. 1c) in macrophages infected with less virulent T. gondii type II strains but not in macrophages infected with virulent type I strains. GRA15 functions downstream of the two adaptor molecules MYD88 and TRIF, which are essential for TLR signalling. This counteracts early infection, as GRA15-deficient T. gondii type II parasites grow fast. GRA24 was identified and shown to traffic from the PV to the host cell nucleus, where it activates genes belonging to the MAPK pathway. GRA24 can interact with the host MAPK p38α (also known as MAPK14) in the cytosol, promoting prolonged autophosphorylation and nuclear translocation of this MAPK. This leads to the activation of the transcription factors EGR1 and FOS, followed by the secretion of key proinflammatory molecules, including IL-12 and the chemokine monocyte chemotactic protein 1 (MCP1; also known as CCL2), which are known to be involved in the control of T. gondii infection |
|
|
Term
| What is Trichomonas vaginalis? |
|
Definition
Sexually transmitted; survives cryopreservation!
Infects urethra, vagina, prostate
Extracellular parasite; feeds on bacteria and cell debris
NO CYST; binary fission
Causes intense inflammation, abortions and infertility
Blocked using physical protection |
|
|
Term
| How can dracunculiasis be prevented? |
|
Definition
|
|
Term
| How can transmission of schistosomiasis be blocked? |
|
Definition
Physical barriers - personal protection
Prevalence control - large-scale treatment of at-risk population groups
Sanitation - access to safe water
Intermediate host control - snail control |
|
|
Term
| How can vector transmission be blocked? |
|
Definition
| Bed nets, traps, biological controls, pesticides, dominant lethal technique, Transmission blocking vaccines |
|
|
Term
| What are the advantages and disadvantages of bed nets? |
|
Definition
cheap prevention method against malaria (Anopheles spp. have nocturnal biting behaviour)
net alone prevents contact only - insecticide-treated nets kill mosquito too (2x as effective as untreated nets)
also curtains, window screens, tents, etc.
Nets aren’t perfect - Glossina and sand flies feed during the day - washing causes loss of insecticidal materia |
|
|
Term
|
Definition
| DDT is inhaled and attacks the insect nervous system: - it targets neuron sodium channels (action potential generation) - open channels disrupt membrane potential of peripheral nervous system - paralysis -> death |
|
|
Term
| What are issues with using DDT? |
|
Definition
| Insect resistance arises from: - channel gene mutations - up-regulation of cytochrome P450 (accelerates DDT metabolism) DDT also persistent: high potential to bioaccumulate |
|
|
Term
| What is the sterile insect technique? |
|
Definition
| A method of controlling vector numbers, large numbers of sterile male vectors released in the wild, sterile males out-compete fertile males, females lay sterile eggs, population decreases. The males are sterilised with gamma rays as pupae, and must be manually seperated from females before release. It also damages mosquitos -the sterile males cannot compete with wild ones |
|
|
Term
| Which vector control technique becomes more effective with decreasing density of the population? |
|
Definition
| sterile insect technique? |
|
|
Term
| What is dominant lethal technique? |
|
Definition
There is a female specific flightless phenotype, with high expression in females and low expression in males
The promoter for this gene is replaced with a tetracyclin-repressible activator (tTAV)
There is still some expression in males, so the ATG of the tTAV is moved upstream of the intron, causing a frameshift mutation in males
This results in females with paralysed wings
Males are still produced and viable - can be released and mate, but females can still be produced in the lab by addition of tetracyclin to feed |
|
|
Term
| How do transmission blocking vaccines work? |
|
Definition
Pfs25 and Pfs28: closely-related, abundant surface membrane proteins. present on zygotes, ookinetes and early oocysts of Plasmodium species - GPI-anchored proteins
Epidermal growth factor (EGF)-like motifs - not glycosylated. role in invasion: cell recognition, binding, and midgut traversal Pfs25/Pfs28 are redundant: double knockout reduces capacity of ookinetes to traverse the midgut and transform into oocysts.
Conserved mechanism of midgut traversal
Essentially, no adaptive immune response in insects. Use recombinant Pfs25 to vaccinate humans (no therapeutic use to individual vaccinated as no Pfs25 on parasite surface)
Antibodies to Pfs25 in a vaccinated individual -> taken up by the mosquito during a bloodmeal. When parasites differentiate in gut, antibodies bind Pfs25/Pfs28 on ookinetes. Surface capping prevents binding functions involved in parasite migration/differentiation. -> protects mosquito from infection, preventing transmission to next host
Algae is used to produce recombinant Pfs25 |
|
|
Term
|
Definition
| They are expressed on the surface of infected red blood cells (iRBCs), bind to RBCs—preferentially of blood group A—to form large rosettes and mediate microvascular binding of iRBCs |
|
|
Term
|
Definition
life-years weighted by quality of life
• 1 QALY = one year in perfect health.
• if an health is below maximum, QALYs are accrued at <1 per year.
• dead = 0 QALYs per year |
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Term
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Definition
| Incidence of ill health in a population |
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Term
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Definition
Disability-adjusted life years – DALY
DALY = YLL + YLD Years of Lost Life (due to premature mortality) Years Lost to Disability (due to injury or illness)
• Number of year lost to ill-health, disability or early death (cf. QALYs)
• Combines information about mortality and morbidity in a single number (cf. QALYs).
• Sum of the number of years lost to premature death and the number of productive years lost to disability.
• One DALY is equivalent to one lost year of healthy life.
• Calculation based on the assumption that everyone has a right to same global life expectancy. |
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Term
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Definition
• They are not highly visible because they do not kill large numbers of rich people;
• They do not cause explosive outbreaks that attract public and media attention;
• They do not travel internationally (vector restriction) so don’t affect wealthy nations;
• They affect the poorest communities => no financial incentive for R&D of new diagnostic tools, drugs and vaccines for diseases with a market that cannot pay;
• Endemic countries have limited resources to invest in health;
• The stigma associated with debilitating and deforming diseases makes the afflicted reluctant to seek care. |
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Term
| What is another name for T. brucei in cattle, and how many domestic animals does it kill? |
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Definition
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Term
| Why are haemoglobinopathies so common, given the severity of the phenotype? |
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Definition
| They can provide increased resistance against malaria and similar diseases |
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Term
| What causes alpha thalassemia? |
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Definition
| Deletions of α globin gene(s) •Symptoms can begin in foetus •Complicated inheritance (4x α genes) |
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Term
| What causes beta thalassemia? |
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Definition
| •Nonsense, splice and frameshift mutations in β globin gene •Symptoms begin in infancy/childhood •Simple autosomal recessive inheritance; genotype-phenotype correlation |
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Term
| What is Glucose 6 phosphate dehydrogenase (G6PD)? |
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Definition
| first enzyme of pentose phosphate pathway - supplies reducing energy (NADPH) to cells - mitochondria are major source of NADPH in most cells - erythrocytes do not contain mitochondria => PPP is only source of NADPH - helps protect erythrocytes against oxidative damage |
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Term
| How does a g6PD deficiency help resistance to parasites? |
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Definition
| Makes cells more prone to oxidative damage |
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Term
| How is the duffy blood group relevant to plasmodium vivax? |
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Definition
Duffy antigen/chemokine receptor (DARC) [a.k.a. Duffy; FY glycoprotein] - receptor that binds cytokines released during inflammation - present on surface of erythrocyte
DARC is also the receptor for Plasmodium vivax merozoite
Erythrocytes lacking duffy/DARC/FY glycoprotein are resistant to P. vivax invasion |
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Term
| Which HDLs have trypanolytic qualities? |
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Definition
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Term
| What is ApoL1, and what is it neccesary for? |
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Definition
ApoL1 is primate specific blood protein with pore-forming properties
ApoL1 is necessary for trypanolytic activity of NHS - Depletion of ApoL1 from normal human serum removes trypanolytic effect - Depletion of other component (haptoglobin-related protein, Hpr) has no effect - Addition of ApoL1 to calf serum (FCS) => trypanolysis |
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Term
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Definition
| Haptoglobin/haemoglobin receptor - necessary for uptake of haem |
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Term
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Definition
A TbHpHbR gene required for lysis by NHS, normally involved in uptake of haem, responsible for uptake and endocytosis of TLF particles TLF particles carry ApoL1
Low pH in lysosome promotes ApoL1 pore formation, leading to influx of Cl-, swelling of the lysosome and cell death |
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Term
| How does T. b. rhodesiense gain resistance to lysis by NHS? |
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Definition
Antigenic variation, not VSG. Gain of resistance to TLF always linked to switch to modified expression site (R-ES) R-ES contains unusual gene: SRA (Serum Resistance Associated)
SRA neutralises ApoL1 activity by interaction with the C-terminal helix of toxin
How the complex is discarded afterwards is unknown. |
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Term
| Why could helminths help treat multiple sclerosis? |
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Definition
| It is exacerbated by inflammation of the CNS, helminths reduce the inflammatory response |
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Term
| Why do we need new drugs for parasites? |
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Definition
the current ones - were designed for other uses
Have high cost
Poor efficacy
High toxicity
Drug resistance
Unsafe for pregnant women/children
Require trained personel |
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Term
| What are the drug discovery phases? |
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Definition
Phase 1 - test drug with around 20-80 people to evaluate safety, safe dosage and side effects
Phase 2 - test drug on 100-300 people to establish efficacy, usually against a placebo
Phase 3 - test on 1000-3000 to confirm effectiveness and compare to existing treatments
Phase 4 - Post marketing studies collect aditional information |
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Term
| What are the advantages and disadvantages to a target based approach to drug discovery? |
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Definition
| Target known, rapid, structure and mechanism based approaches are possible, and can apply strict entry criteria, but does not addresss druggability issues (e.g. permeability, selectivity), Does not identify pro-drugs or drugs acting via lethal synthesis, and may make resistance more likely |
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Term
| What are the entry criteria for drug discovery? |
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Definition
Target validation
Druggability - known inhibitors and active site known to be druggable
Assay feasibility - Supply assured
Potential ttoxicity
Potential resistance
Structural information |
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Term
| What are the four main methods of acquiring resistance to a drug? |
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Definition
Drug inactivation via modification of the drug
Altered metabolic pathway
Altered target site
Altered uptake of drug |
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Term
| What was the most powerful malaria drug? |
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Definition
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Term
| How does chloroquine work? |
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Definition
Plasmodium digests Hb in food vacuole creating non-toxic haemozoin precipitate
CQ diffuses and is transported to food vacuole Inside vacuole, acidic pH charges CQ, trapping it (no longer able to diffuse across membrane)
CQ in vacuole interferes with haemozoin production - Causing build up of toxic by-product instead |
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Term
| What confers chloroquine resistance? |
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Definition
A single mutation confers CQ resistance
Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) - 10 TM domain transporter-like protein, found in food vacuole membrane PfCRT is highly polymorphic protein
All CQ-resistance parasites share single mutation (Lys-76 to Thr)
Mutant PfCRT prevents CQ build up in food vacuole K76T mutation appears to confer ability of PfCRT to transport charged CQ
Creates flux of CQ out of vacuole
Hence preventing accumulation |
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Term
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Definition
| An antimalarial drug which falciparum is gaining resistance too - we dont know how it works or the resistance works |
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