Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecule to Malady > Lecture 16 + 17 - Malaria > Flashcards

Lecture 16 + 17 - Malaria Flashcards

1
Q

Age group most represented in malaria deaths

A

Children under 5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Phylum of malaria

A

Apicomplexia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Genus of malaria

A

Plasmodium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q 
Plasmodium species that infect humans
1)
2)
3)
4)
A

1) Falciparum
2) Vivax
3) Ovalae
4) Malariae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Primate - human plasmodium pathogen

A

Plasmodium knowlesi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How does plasmodium gain access to hepatocytes?

A

Kupfer cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

3 places where plasmodium live

A

Mosquito, human hepatocytes, human erythrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Example of the strength of anti-malarial selective pressure

A

Sickle-cell anaemia alleles are maintained in sub-Saharan Africa, as being heterozygous for this reduces susceptibility to malaria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Difference in P. vivax and P. falciparum infection

A

Vivax causes more severe morbidity, but is less likely to kill

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Number of malaria deaths per year

A

~650,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the gold crystals observed in malaria-infected erythrocytes?

A

Haemozin
Parasite eats haemoglobin, but haem is toxic.
Crystallises haem to haemozoin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Malaria definitive host

A

Mosquito (where sexual reproduction of gametocytes occurs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why are malarial infections comparable between Latin America and sub-Saharan Africa, but sub-Saharan Africa has much higher mortality rates?

A

P. vivax more common in Latin America.

P. falciparum more common in sub-Saharan Africa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Estimated number of malaria cases per year

A

300 - 500 million

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Amount of household spending on malaria in Africa

A

Estimated 10% of household spending (mosquito nets, medication ,etc)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q 
P. falciparum life cycle
1) a, b, c
2) a, b
3) a, b
4)
A

1) Mosquito stage (in mosquito gut)
a) Gamete
b) Zygote
c) Ookinete

MOSQUITO BITES HUMAN

2) Hepatocyte stage
a) Sporozoites infect hepatocytes
b) Merozoites form, exit hepatocytes

3) Blood stage
a) Merozoites infect erythrocytes, divide rapidly
b) Gametocytes form

4) Mosquito ingests gametocytes from human host, sexual reproduction in mosquito

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

When does malaria cause illness?

A

During merozoite stage

Hepatocyte stage is asymptomatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Number of infected erythrocytes directly after hepatocyte stage Vs number of infected erythrocytes after merozoite expansion

A

10^3 infected erythrocytes Vs 10^11 infected erythrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does merozoite release coincide with?

A

Periodic fever, cytokine storm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Basic overview of three stages of malarial infection

A

Mosquito stage - Sexual reproduction
Hepatocyte stage - Asexual reproduction
Erythrocyte stage - Asexual reproduction, major amplification stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where does the sexual stage occur, and for how long?

A

1 - 2 weeks in female Anopheles mosquito

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How long does it take for injected sporozoites to enter hepatocytes from skin?

A

~30 minutes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How long does the asexual liver stage last for?

A

~1-2 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How long after infection does disease occur?

A

~1 month

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How long does the asexual erythrocyte stage last for?

A

~2-3 days, is quite synchronous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Symptoms of malaria

A

Fever, chills, anaemia, coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Proportion of malaria deaths caused by P. falciparum

A

95%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

How does P. vivax cause relapsing malaria?

A

Hypnozoites in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What role does cytoadherence play?

A

Malaria doesn’t want infected blood cells to enter the spleen, as they would be destroyed there.

Instead, cause infected erythrocytes to adhere to vascular wall.

30
Q

What coincides most with malarial death?

A

Infected erythrocytes adhering to walls of blood vessels in brain.

Exact mechanism of death not known. Not straight ischaemia

31
Q

What adheres infected erythrocytes to the vascular wall?

A

PfEMP1

32
Q

PfEMP1 role

A

Binds to molecules on microvascular endothelium

33
Q

Surface protein in the brain microvasculature that PfEMP1 binds to

A

ICAM1

34
Q

Number of different genomic copies of PfEMP1 in a malarial genome

A

Over 60

35
Q

Name of genes encoding PfEMP1

A

var genes

36
Q

How are different var genes expressed?

A

Epigenetic silencing of all var genes except for 1.

A parasite can change var gene expression

37
Q

What correlates with different waves of parasitaemia?

A

Expression of different PfEMP1 genes

Express different ones when an effective antibody response is launched against one

38
Q

Where are most var genes located?

A

Sub-telomeric regions of chromosomes

39
Q

Why do different P. falciparum parasites have a greater variety of var genes than expected?
1)
2)
3)

A

1) Chromosomes cluster at at nuclear periphery of parasite
2) Recombination between heterologous chromosomes that are clumped together, aligned
3) Results in great variation of var genes and expressed PfEMP1s

40
Q

Number of proteins that P. falciparum exports into erythrocyte cytoplasm

A

Hundreds

41
Q

KAHRP function

A

Knob formation.

Knob allows parasite to hang onto microvascular endothelium under flow pressure

42
Q

Evidence for KAHRP function

A

With KAHRP, infected RBC surface is rough, cell sticks to microvascular endothelium

Without KAHRP, infected RBC surface is smooth, doesn’t stay attached to vascular wall

43
Q

Motif allowing P. falciparum to export proteins into RBC cytoplasm

A

PEXEL motif

44
Q

Amount of P. falciparum proteome estimated to be exported out of parasite

A

~5%

45
Q

PEXEL motif role

A

Allow proteins to cross parasitophorous vacuole membrane

46
Q

Two important sites in P. falciparum protein export

A

1) Endoplasmic reticulum

2) Parasitophorous vacuole membrane

47
Q

What is PEXEL?

A

A protease cleavage site

Cleaved by Plasmepsin IV

48
Q

What does plasmepsin IV cleave?

A

PEXEL motif, in the endoplasmic reticulum

49
Q

Where is PEXEL cleaved by plasmepsin IV?

A

RxLxE/Q/D –> RxL | xE/Q/D

In the ER

50
Q

Where is plasmepsin IV present?

A

In the ER of P. falciparum

51
Q

PTEX

A

A putative translocon of PEXEL proteins

52
Q 
Criteria for PTEX
1)
2)
3)
4)
A

1) Plasmodium-specific, in the correct location
2) Essential to blood-stages
3) Energy source, a protein-unfolding mechanism
4) Binds transiting cargo PEXEL proteins

53
Q

PTEX structure
1)
2)
3)

A

1) 5 proteins
2) HSP101 is an energy source, unfolds proteins so that they can fit through pore
3) EXP2 is a pore protein

54
Q

PTEX location

A

Parasitiphorous vacuole membrane in RBC

55
Q

How long does it take for a merozoite to enter an erythrocyte?

A

~30 seconds

56
Q

Possible anti-malarial drug targets
1)
2)

A

1) Plasmepsin IV

2) PTEX

57
Q

Types of anti-malarial vaccine
1)
2)
3)

A

1) Pre-erythrocytic
2) Transmission-blocking
3) Blood-stage (anti-merozoite)

58
Q

Example of possible pre-erythrocytic vaccine

A

RTS, S

In stage III clinical trials

59
Q

Difficulty for anti-merozoite antibodies

A

Only have about 1.5 minutes when merozoites are susceptible to action.

~1.5 minutes between when merozoites exit former host cell, enter erythrocyte

60
Q

Primary interaction target of possible vaccine

A

Binding to cell

61
Q 
Secondary interaction target of possible vaccines
1)
2)
3)
4)
5)
A

1) Actin/myosin motor
2) Surface protein shedding
3) Secondary ligand shedding
4) Resealing
5) Recovery from echinocytosis

62
Q 
Problems with making an anti-malaria vaccine
1)
2)
3)
4)
A

1) Empirical vaccine techniques aren’t working
2) Very little functional knowledge of individual antigens
3) Many antigens are identified, but which to target?
4) Vaccine must cover three major invasion pathways

63
Q

Target of P. vivax on erythrocytes

A

Duffy protein

64
Q

Adaptation of West Africans against P. vivax

A

Don’t express Duffy protein on erythrocyte membrane

As a result, no P. vivax in West Africa

65
Q

Families of surface proteins that bind erythrocytes in P. falciparum

A

1) EBA (erythrocyte-binding antigen) (5 members)

2) PfRh (5 members)

66
Q

What does the W2mef strain of P. falciparum use to bind erythrocytes?

A

Can use EBA175 to bind sialic acid on GlyA

67
Q

What does W2mef strain do when RBCs have been depleted of sialic acid by neuraminidase?

A

Expresses a silaic acid-independent invasion phenotype using a different surface ligand (Rh4)

68
Q

Important targets of inhibitory antibodies

A

EBA, Rh proteins

69
Q

Why does P. falciparum use several invasion pathways?
1)
2)

A

1) Accommodate RBC polymorphism

2) Immune avoidance

70
Q

Major invasion pathways now identified

A

Three major invasion pathways

Molecule to Malady (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions