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Parasitology > Malaria evolutionary pressure > Flashcards

Malaria evolutionary pressure Flashcards

1
Q

How many malaria related deaths in 2015?

A

429,000

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2
Q

How many people were infected with malaria in 2015?

A

212 million

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3
Q

Malaria is not present in which subtropical/tropical areas?

A
  • Areas without local Anopheles populations
  • Deserts
  • During cooler seasonal periods
  • At high altitudes
  • In regions where malaria has been successfully eradicated
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4
Q

Where can malaria be found all year round?

A

In countries located near the equator

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5
Q

Where is malaria most prevalent?

A

Sub-saharan africa

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6
Q

Why is malaria not present in the US/ Western Europe?

A
  • Due to the prosperity of the economy

- Due to successful malaria eradication programmes

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7
Q

Why is global warming a threat?

A

Many regions in which malaria has been eradicated still contain Anopheles species which are capable of transmitting malaria; therefore, climate change may cause malaria to re-infect these areas

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8
Q

In cooler regions which Plasmodium is more common?

A

Plasmodium vivax, more tolerant to cooler temperatures

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9
Q

Why does malaria impose such a great selection pressure?

A

As it kills a large fraction of the population before reproductive age
It causes higher fatality in children than adults
This imposes a great selection pressure for any mutations which may confer resistance to malaria as these are more likely to be spread as the adults carrying them reach reproductive age

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10
Q

How many malaria associated deaths in 2015?

A

429,000

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11
Q

Where are the most haemoglobinopathies seen?

A

In areas where malaria is endemic

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12
Q

What are haemoglobinopathies?

A

Haemoglobinopathies are inherited haemoglobin disorders

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13
Q

How does malaria cause death?

A
  • Severe forms of malaria such as placental and cerebral malaria due to the PfEMP1 variants
  • Malaria causes death due to the occlusion of blood vessels which is caused by cytoadherence of RBC to endothelial cells, platelet mediated clumping and rosetting of red blood cells
  • Cytokine storm
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14
Q

Occlusion of blood vessels can lead to?

A
  • Hypoxia= not enough oxygen reaching the tissues and cells

- Anaerobic glycolysis= a build up of lactic acid

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15
Q

What is the structure of red blood cells?

A
  • Biconcave disks
  • Dumbbell shaped with the centre being flattened/depressed
  • High surface area to volume ratio
  • 8 micrometers in diameter
  • Contains haemoglobin
  • Flexible
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16
Q

What is the shape of red blood cells?

A

Biconcave disk

Dumbbell shaped due to a depressed/flattened centre

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17
Q

What is the diameter of red blood cells?

A

8 micrometers

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18
Q

Why are red blood cells flexible?

A

To facilitate their movement within tight capillaries

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19
Q

Red blood cells lack?

A
  • Nucleus
  • Organelles
  • ATP production
  • MHC
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20
Q

Red blood cells do not express what on their surfaces?

A

They do not express MHC

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21
Q

How long do red blood cells live?

A

90-120 days

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22
Q

What is the erythrocyte membrane made up of?

A

Spectrins and ankyrins maintain the biconcave shape of the red blood cell

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23
Q

What makes up the RBC cytoskeleton?

A

Spectrins and ankyrins

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24
Q

Lifespan of red blood cells?

A

90-120 days

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25
Q

When red blood cells age they?

A

Loose their shape

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26
Q

Red blood cells are removed by?

A

Macrophages in the liver and spleen

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27
Q

What is haemoglobin?

A

A protein which is a transporter of oxygen

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28
Q

Haemoglobin structure?

A

Made up of 4 polypeptides

Each polypeptide is associated with a haem group

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29
Q

Adult haemoglobin structure?

A

4 polypeptides

2 alpha and 2 beta polypeptides

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30
Q

What is haem?

A

A non-protein prosthetic group

A porphyrin ring which contains an iron ion

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31
Q

How many oxygen molecules can a single haemoglobin molecule bind to?

A

4 oxygen molecules

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32
Q

How many haem groups are associated with a single haemoglobin molecule?

A

4 haem groups

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33
Q

Haem turns what colour when bound to oxygen?

A

Red

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34
Q

Where can myoglobin be found?

A

Tissues

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35
Q

What is myoglobin?

A

An oxygen acceptor

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36
Q

Myoglobin structure?

A

Made of a single polypeptide chain which is associated with a single haem group

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37
Q

Main difference between haemoglobin and myoglobin?

A

Myoglobin is an oxygen acceptor but haemoglobin is an oxygen transporter
Myoglobin has a higher affinity for oxygen
Myoglobin is made of a single polypeptide chain but haemoglobin is made up of four

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38
Q

Myoglobin has a higher?

A

Affinity for oxygen than haemoglobin

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39
Q

Diving animals have?

A

Higher concentrations of myoglobin in their tissues which allows them to hold their breath for longer

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40
Q

What are the two states of haemoglobin?

A

Taut form

Relaxed form

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41
Q

When does haemoglobin form the taut conformation?

A
  • Low pH
  • High CO2 concentrations
  • Low partial pressure of oxygen
  • In the tissues
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42
Q

The taut form of haemoglobin leads to the?

A

Release of oxygen

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43
Q

When does haemoglobin form the relaxed conformation?

A
  • High pH
  • Low CO2 concentrations
  • High partial pressure of oxygen
  • In the lung
44
Q

The relaxed form of haemoglobin leads to the?

A

Uptake of oxygen

45
Q

Compare affinities of the taut and relaxed haemoglobin forms?

A

Taut form has low affinity for oxygen

Relaxed form has a high affinity for oxygen

46
Q

Genes for haemoglobin A chains can be found on which chromosome?

A

16

47
Q

Genes for haemoglobin B chain can be found on which chromosome?

A

11

48
Q

How many haemoglobin A chain genes are there and what are they called?

A

2

HBA1 and HBA2

49
Q

How many genes for B chain of haemoglobin?

A

A single gene

50
Q

How many genes for A chain in a cell?

A

4

51
Q

How many genes for B chain in a cell?

A

2

52
Q

What are the different types of haemoglobin?

A

HbA
HbA2
HbF

53
Q

Which form of haemoglobin is the most common in adults?

A

HbA

54
Q

Which form of haemoglobin is less common in adults?

A

HbA2

55
Q

Which form of haemoglobin is foetal haemoglobin?

A

HbF

56
Q

Foetal haemoglobin has a higher affinity for?

A

Oxygen

57
Q

HbA2 is made up of which chains?

A

Alpha 2

Delta 2

58
Q

HbA is made up of which chains?

A

Alpha 2

Beta 2

59
Q

HbF is made up of which chains?

A

Alpha 2

Gamma 2

60
Q

Which type of globin chain is required to form every type of haemoglobin?

A

Alpha globin chain

61
Q

What are the non-alpha globin chains?

A

Epsilon, gamma, delta, bea

62
Q

When is HbF most prevelant?

A

7 months up until birth

63
Q

When is foetal haemoglobin replaced by adult haemoglobin?

A

Within 6 months post-birth

64
Q

Why does foetal haemoglobin have a higher affinity for oxygen than adult haemoglobin?

A

To provide the foetus with better access to oxygen in the mother’s bloodstream

65
Q

What are inherited haemoglobin disorders known as?

A

Haemoglobinopathies

66
Q

What are the two main types of haemoglobinopathies?

A

The main types of haemoglobinopathies include:

  • Thalassaemia
  • Variant/abnormal haemoglobin
67
Q

What are the two forms of thalassaemia?

A

Alpha thalassaemia

Beta thalassaemia

68
Q

What is thalassaemia?

A

A haemoglobinopathy

It is when there is reduced production/no production of a specific globin chain

69
Q

What is beta thalassaemia?

A

This is when there is reduced or no production of the beta chain

70
Q

What is major beta thalassaemia?

A

Both genes of HBB are affected

No beta chain production

71
Q

What is the impact of beta thalassaemia?

A

Most foetal haemoglobin is replaced by adult haemoglobin within 6 months post-birth
Will lead to severe anaemia within the first year of life

72
Q

What is required to survive beta thalassaemia?

A

Blood transfusions for life

Haemopoietic stem cell transplant in childhood

73
Q

What could cure beta thalassaemia?

A

Finding a way of increased foetal haemoglobin production

74
Q

When is alpha thalassaemia the most severe?

A

When impacting more than two/all of the alpha haemoglobin chain encoding genes

75
Q

If all four genes of the alpha chain are impacted?

A

The foetus is highly unlikely to survive gestation

76
Q

What are thalassaemia disorders?

A

Reduced or no production of normal alpha/beta haemoglobin chains

77
Q

Most common abnormal/variant haemoglobin haemoglobinopathy?

A

Sickle cell disease

78
Q

What causes sickle cell disease?

A

A point mutation in the beta haemoglobin gene of chromosome 11

79
Q

The point mutation leads to which amino acid substitution?

A

Glutamate –> Valine

80
Q

Valine is?

A

A hydrophobic amino acid

81
Q

When do the sickle cells form?

A

Triggered by the taut conformation of haemoglobin which occurs at low pH, high CO2, at low partial pressures of oxygen in the tissues

82
Q

How does the taut form of haemoglobin cause sickle cells?

A

The taut form exposes a hydrophobic surface region. Causes haemoglobins to aggregate instead of interacting with the cellular environment. This causes fibres to form and the sickle celled shape

83
Q

What can sickle cell lead to?

A

Blood vessel occlusion

Lower oxygen availability

84
Q

How is sickle cell a self sustained process?

A

Sickle cells cause blood vessel occlusion which leads to even lower oxygen availability causing more red blood cells to become sickle shaped

85
Q

What is the variant of haemoglobin which leads to sickle cell called?

A

HbS

86
Q

Fibre formation is only formed why which haemoglobin conformation?

A

Taut form of haemoglobin

87
Q

Characteristics of sickle cells?

A

Sickle shaped
Can lead to blood vessel occlusion
Lifespan of 20 days

88
Q

Sickle cells have a life span of?

A

20 days

89
Q

Which genotype protects you from malaria with regards to sickle cell?

A

Homozygous for sickle cell mutation

Heterozygous for the sickle cell mutation

90
Q

What is the issue with being homozygous for sickle cell?

A

Fitness cost

Die of sickle cell

91
Q

As the heterozygote has an advantage and is being selected for this can be known as?

A

Heterozygote advantage

Overdominance

92
Q

How does sickle cell protect from malaria?

A
  • Sickle shape of the red blood cell is less likely to adhere to endothelial cells due to PfEMP1
  • Red blood cell intracellular environment is altered
  • Lower levels of parasite growth
  • Red blood cells have a lifespan of 20 days, the parasite takes 2-3 days to develop in a RBC, more likely that the parasitised RBC will be removed by macrophages
  • Parasite mutation decreases
93
Q

What is the duffy antigen?

A

This is a chemokine receptor located on the surface of red blood cells

94
Q

Duffy antigen is involved in?

A

Chemokine bufferring

95
Q

The duffy antigen is a receptor for?

A

Plasmodium vivax and Plasmodium knowlesi

96
Q

Duffy phenotypes?

A

Fy a+ b+
Fy a+ b-
Fy a- b+
Fy a- b-

97
Q

Which genotype is most prevalent in Africa?

A

Duffy silent allele

Fy a-b-

98
Q

Which allele protects from Plasmodium vivax/knowlesi infection?

A

Duffy antigen silent allele

Fy a-b-

99
Q

Where else can duffy antigen be expressed?

A

Endothelial cells

In other tissues: Brain, kidney, spleen, heart, lung

100
Q

Duffy antigen is encoded by a gene known as?

A

DARC

101
Q

Individuals homozygous recessive for the Fy silent allele are protected from?

A

P.vivax and P.knowlesi

102
Q

Individuals homozygous recessive for the Fy silent allele do not express what on their red blood cells?

A

Duffy antigen

103
Q

Individuals homozygous recessive for the Fy silent allele do however express duffy antigen on?

A

Other tissues where it is normally expressed: brain, lung, liver, kidney, spleen, endothelial cells

104
Q

How is Duffy antigen expression repressed on red blood cells alone?

A

Due to a mutation in the promoter for the DARC gene

The GATA transcription factor cannot bind which prevents Duffy antigen expression on red blood cells

105
Q

As Duffy negative individuals still express Duffy antigen on other cell types?

A

They have a normal phenotype

There is no negative fitness cost

Parasitology (17 decks)

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