Week 11 Flashcards
1
Q
current challenges of malaria
A
- resistance to drugs
- mosquitos resistance to insecticides
- environmental changes: re-introduction of vector into regions where it had been eradicated
2
Q
Disease symptoms
A
depends on:
1. species involved
2. host health and immunity
3
Q
Insect cycle of Plasmodium spp (malaria)
A
- infectious stage is gametes
- gametes combine to form zygote
- then makes ookinete then oocyst
- oocysts make lots of copies
- get released as sporozoites
4
Q
Human cycle in Plasmodium spp (malaria)
A
Two cycles in the human host
1. Exo-erythrocytic (1 time)
- happens in the liver to establish infection
2. Erythrocytic (many times)
- happens in RBCs
- responsible for pathology
5
Q
What are the 4 stages of the cycles?
A
- Invasion
- Nutrient uptake
- Asexual replication
- Liberation or release
6
Q
Invasion
A
- Different species have different tropism
- Driven by receptor availability
- P. vivax – young RBCs: Also requires Duffy Ag on RBC surface.
- P. malariae – senescent (old) RBCs.
- P. falciparum – all RBCs
7
Q
What is the first immune evasion strategy of Plasmodium spp
A
hide in cells
8
Q
Nutrient uptake in Plasmodium spp
A
- parasites eat hemoglobin
- Parasite takes in HB via cytostome
- digested in the digestive vacuole
- releases heme (toxic) and strips off the amino acids (uses it for replication)
9
Q
Heme storage
A
- toxic
- stack it and store it so it doesn’t come into contact with the rest of the body
- Some may enter mitochondrion
- Most rendered harmless and stored as hemozoin
10
Q
Hemezoin
A
- crystal form of heme
- heme stacked up
- kept in digestive vacuole
- once parasite bursts out of RBC, gets left in your bloodstream which causes high fevers
11
Q
Artemisinin
A
- synthetic derivative from sweet wormwood
- prodrug (has to be activated to become toxic)
- heme activates it by cleaving it into an active compound
- mechanism not fully known
- promiscuous (binds lots of targets in RBC)
- Process of activation also releases free radicals that may damage parasite directly
- resistance becoming an issue
12
Q
Resistance mechanisms of parasites to drugs
A
- take in less hemoglobin
- reduces toxicity of drug because less heme available to cleave it
- trade off is that you grow slower - efflux pumps (common)
- cell surface pumps that will take the drug and pump it out of the cell
13
Q
Replication
A
- asexual in human host
- process is schizogony
- parasites digest vacuolar membrane then rupture host cell to escape
- Merozoites released into blood
- Cellular contents warn the
immune system - Hemozoin is toxic, induces TNFa – fever
14
Q
Attachment
A
- By chance they contact an RBC
- must determine whether RBC is suitable (proper receptors/age)
- reorients apical complex for attachment
15
Q
Formation of the tight junction
A
- after attachment
- Release of high-affinity proteins from micronemes and rhoptries
- RON complex forms a tight/moving junction with the plasma membrane of the RBC (physical connection between parasite/host PMs)
