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Integrated Biology Module II Difficult
Concepts Exam Study Guide.
Cell invasion is a common phenomenon in the life cycle of Plasmodium. List the number of
times Plasmodium invades cells, and add a brief comment on what cell type is being invaded
(e.g. merozoite invades human red blood cell). Do not repeat (e.g. listing 10 times that a
merozoite invades a red blood cell). Consider both the human and mosquito hosts. -
answer✔1.sporozoite into liver cells in humans
2.merozoite into red blood cells in humans
3. ookinete through mosquito gut wall cells
4.sporozoite through mosquito salivary gland cells
An argument can be made that the ookinete does not actually invade (as in live in host cell). This
is correct (we mentioned it in class), but there is certainly movement into the cell.
In the lecture presentation on the origin of Plasmodium falciparumI started mentioning the
results of a study by Perkins & Schall that showed that the closest relative of P. falciparum was
P. reichenowi. We now believe that the closest relative of P. falciparum lived on a gorilla. Was
the result of Perkins & Schall incorrect? - answer✔no
In short, the relationships implied by Perkins & Schall or Rich et al. are totally consistent with
the relationships proposed by Liu et al. The one difference is more data, which allows a
presumably better/more detailed hypothesis. Perkins et al is incomplete, but not wrong.
Imagine a new discovery in malaria research. Some research group figures out a way to block
infected red blood cells from binding with ICAM-1 in the brain. However, the procedure does
not affect binding with receptor proteins in capillaries in other parts of the body. Armed with the
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knowledge you acquired during this module, what is the best/most appropriate response to this
news? - answer✔This may lower the number of cases of severe malaria
Basic data: We know from lecture that ICAM -1 is the specific receptor in the capillaries of the
brain. Receptors in other parts of the body are different. Second, complicated malaria very often
involves the brain (cerebral malaria). Taking these two together, this research group may have
found a way to limit the amount of cerebral / complicated malaria, by preventing sequestration in
brain capillaries. We cannot exclude symptoms because of sequestration in other parts of the
body, and this might be serious, but their solution may prevent cerebral malaria.
In what country was Modiano et. al. study done? - answer✔Burkina Faso
What is the expectation for initial spread of a new allele that provides strong protection against
malaria as a heterozygote (like HbS). There are only very minor negative side effects in the
heterozygote. Pick the best answer given the information provided - answer✔It will spread fast
Given the information provided this is the best answer. 2) could be correct but it assumes things I
never told you (for this question)
In Table 2 of Modiano et. al., when testing for the effect of genotype in comparisons between
healthy subjects and malarial patients the authors come up with an odds ratio of 0.71 and P value
of 0.0008 for individuals with AC. What is their conclusion? - answer✔AC confers some
protection against malaria
The authors of Modiano et. al wanted to know what effect, if any, HbC has on the probability to
get malaria, non-complicated or severe. What is the null hypothesis for the analysis these authors
did in their paper and we did in "lecture"? - answer✔HbC has no effect on the probability of
getting non-complicated malaria
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The Bloland paper sets up a framework of items to be considered when developing appropriate
drug treatments for malaria (and other diseases) that limit development of resistance Which of
the following are recommended?
1. Improved diagnostics to limit unnecessary use of drugs 2.Procedures to improve patient
compliance, such as directly observed therapy
3.Use of combination therapies
4.All of the above - answer✔4. All of the above
Which of the following candidate combinations for combination therapy would be expected to
retain effectiveness the longest? Why? - answer✔Tetracycline + mefloquine
The key was to find a combination that has different modes of action. 1) are both artemisinin
derivatives, 2) both 4-amino-quinolines; 4) both dihydrofolate reductase inhibitors. But
Tetracycline (antibiotic) and mefloquine (quinoline-methanol) are quite different. Whether this
combination should actually be used is a different matter, but they definitely modes of action.
In the Bloland paper, Conrad & Rosenthal note that a potential disaster could happen if extensive
resistance to artemisinin combination drugs would appear in Africa. However, they note that
such resistance is not evident right now. In fact they propose using the current "good times" to
expand use of a few specific artemisinin combinations for preventative therapy (e.g. IPT). Think
of the positives and negatives of such a strategy. Next write a few sentences on your response.
This might be a strong view in favor or against (please explain why) or one or more questions
that you feel should be answered before making a decision (list questions and why). I am looking
for considered opinions, not specific answers. - answer✔
A major consideration in drug development is that the drug to be developed does not do major
damage to the host. In that context, drugs targeting the apicoplast are very attractive in terms of
treating malaria patients. Explain why this would be? - answer✔Apicoplast is a reduced
chloroplast and thus basically bacterial in origin ==> antigens that are unlikely to be present in
host mammals. Apicoplast can be attacked using antibiotics which are not likely to target
mammalian tissues
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What response will occur to a merozoite in a RBC by the immune system.
A humeral system, a cell mediated system, both, or neither? - answer✔neither
What response will occur to a merozoite in the blood stream by the immune system.
A humeral system, a cell mediated system, both, or neither? - answer✔humeral system
What response will occur to a sporozoite in liver cell by the immune system.
A humeral system, a cell mediated system, both, or neither? - answer✔cell mediated system
What response will occur to a gametocyte in a RBC by the immune system.
A humeral system, a cell mediated system, both, or neither? - answer✔neither
In the videos Dr. Klompen made a big deal out of the importance of memory cells. He also
mentioned that Plasmodium in medium to high infections appears to be able to reduce the
proportion of activated lymphocytes that change into memory cells. In other words, more cells
develop into e.g. plasma cells. What is the main effect of this on our ability to resist malaria? -
answer✔It hurts us long term by preventing build top of natural immunity too Plasmodium.
The entire concept of immunity is based on the formation of memory cells. Break that up, and
natural immunity disappears
What is the main added value of phase 3 trials over phase 1 and 2 trials: - answer✔Use far more
individuals, so they may detect rare side effects, and document efficacy in a larger diversity of
individuals
This is taken directly from the MVI pamphlet. As an aside, when developing Covid vaccines,
phases 1 and 2 went superfast, phase 3 trials take many people and take some time. The Pfizer
vaccine appears to have finished abbreviated phase 3 trials
