1
Q
How many malaria related deaths in 2015?
A
429,000
2
Q
How many people were infected with malaria in 2015?
A
212 million
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
4
Q
Where can malaria be found all year round?
A
In countries located near the equator
5
Q
Where is malaria most prevalent?
A
Sub-saharan africa
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
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
8
Q
In cooler regions which Plasmodium is more common?
A
Plasmodium vivax, more tolerant to cooler temperatures
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
10
Q
How many malaria associated deaths in 2015?
A
429,000
11
Q
Where are the most haemoglobinopathies seen?
A
In areas where malaria is endemic
12
Q
What are haemoglobinopathies?
A
Haemoglobinopathies are inherited haemoglobin disorders
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
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
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
16
Q
What is the shape of red blood cells?
A
Biconcave disk
Dumbbell shaped due to a depressed/flattened centre
17
Q
What is the diameter of red blood cells?
A
8 micrometers
18
Q
Why are red blood cells flexible?
A
To facilitate their movement within tight capillaries
19
Q
Red blood cells lack?
A
- Nucleus
- Organelles
- ATP production
- MHC
20
Q
Red blood cells do not express what on their surfaces?
A
They do not express MHC
21
Q
How long do red blood cells live?
A
90-120 days
22
Q
What is the erythrocyte membrane made up of?
A
Spectrins and ankyrins maintain the biconcave shape of the red blood cell
23
Q
What makes up the RBC cytoskeleton?
A
Spectrins and ankyrins
24
Q
Lifespan of red blood cells?
A
90-120 days
25
When red blood cells age they?
Loose their shape
26
Red blood cells are removed by?
Macrophages in the liver and spleen
27
What is haemoglobin?
A protein which is a transporter of oxygen
28
Haemoglobin structure?
Made up of 4 polypeptides
| Each polypeptide is associated with a haem group
29
Adult haemoglobin structure?
4 polypeptides
| 2 alpha and 2 beta polypeptides
30
What is haem?
A non-protein prosthetic group
| A porphyrin ring which contains an iron ion
31
How many oxygen molecules can a single haemoglobin molecule bind to?
4 oxygen molecules
32
How many haem groups are associated with a single haemoglobin molecule?
4 haem groups
33
Haem turns what colour when bound to oxygen?
Red
34
Where can myoglobin be found?
Tissues
35
What is myoglobin?
An oxygen acceptor
36
Myoglobin structure?
Made of a single polypeptide chain which is associated with a single haem group
37
Main difference between haemoglobin and myoglobin?
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
38
Myoglobin has a higher?
Affinity for oxygen than haemoglobin
39
Diving animals have?
Higher concentrations of myoglobin in their tissues which allows them to hold their breath for longer
40
What are the two states of haemoglobin?
Taut form
| Relaxed form
41
When does haemoglobin form the taut conformation?
- Low pH
- High CO2 concentrations
- Low partial pressure of oxygen
- In the tissues
42
The taut form of haemoglobin leads to the?
Release of oxygen
43
When does haemoglobin form the relaxed conformation?
- High pH
- Low CO2 concentrations
- High partial pressure of oxygen
- In the lung
44
The relaxed form of haemoglobin leads to the?
Uptake of oxygen
45
Compare affinities of the taut and relaxed haemoglobin forms?
Taut form has low affinity for oxygen
| Relaxed form has a high affinity for oxygen
46
Genes for haemoglobin A chains can be found on which chromosome?
16
47
Genes for haemoglobin B chain can be found on which chromosome?
11
48
How many haemoglobin A chain genes are there and what are they called?
2
| HBA1 and HBA2
49
How many genes for B chain of haemoglobin?
A single gene
50
How many genes for A chain in a cell?
4
51
How many genes for B chain in a cell?
2
52
What are the different types of haemoglobin?
HbA
HbA2
HbF
53
Which form of haemoglobin is the most common in adults?
HbA
54
Which form of haemoglobin is less common in adults?
HbA2
55
Which form of haemoglobin is foetal haemoglobin?
HbF
56
Foetal haemoglobin has a higher affinity for?
Oxygen
57
HbA2 is made up of which chains?
Alpha 2
| Delta 2
58
HbA is made up of which chains?
Alpha 2
| Beta 2
59
HbF is made up of which chains?
Alpha 2
| Gamma 2
60
Which type of globin chain is required to form every type of haemoglobin?
Alpha globin chain
61
What are the non-alpha globin chains?
Epsilon, gamma, delta, bea
62
When is HbF most prevelant?
7 months up until birth
63
When is foetal haemoglobin replaced by adult haemoglobin?
Within 6 months post-birth
64
Why does foetal haemoglobin have a higher affinity for oxygen than adult haemoglobin?
To provide the foetus with better access to oxygen in the mother's bloodstream
65
What are inherited haemoglobin disorders known as?
Haemoglobinopathies
66
What are the two main types of haemoglobinopathies?
The main types of haemoglobinopathies include:
- Thalassaemia
- Variant/abnormal haemoglobin
67
What are the two forms of thalassaemia?
Alpha thalassaemia
| Beta thalassaemia
68
What is thalassaemia?
A haemoglobinopathy
| It is when there is reduced production/no production of a specific globin chain
69
What is beta thalassaemia?
This is when there is reduced or no production of the beta chain
70
What is major beta thalassaemia?
Both genes of HBB are affected
| No beta chain production
71
What is the impact of beta thalassaemia?
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
What is required to survive beta thalassaemia?
Blood transfusions for life
| Haemopoietic stem cell transplant in childhood
73
What could cure beta thalassaemia?
Finding a way of increased foetal haemoglobin production
74
When is alpha thalassaemia the most severe?
When impacting more than two/all of the alpha haemoglobin chain encoding genes
75
If all four genes of the alpha chain are impacted?
The foetus is highly unlikely to survive gestation
76
What are thalassaemia disorders?
Reduced or no production of normal alpha/beta haemoglobin chains
77
Most common abnormal/variant haemoglobin haemoglobinopathy?
Sickle cell disease
78
What causes sickle cell disease?
A point mutation in the beta haemoglobin gene of chromosome 11
79
The point mutation leads to which amino acid substitution?
Glutamate --> Valine
80
Valine is?
A hydrophobic amino acid
81
When do the sickle cells form?
Triggered by the taut conformation of haemoglobin which occurs at low pH, high CO2, at low partial pressures of oxygen in the tissues
82
How does the taut form of haemoglobin cause sickle cells?
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
What can sickle cell lead to?
Blood vessel occlusion
| Lower oxygen availability
84
How is sickle cell a self sustained process?
Sickle cells cause blood vessel occlusion which leads to even lower oxygen availability causing more red blood cells to become sickle shaped
85
What is the variant of haemoglobin which leads to sickle cell called?
HbS
86
Fibre formation is only formed why which haemoglobin conformation?
Taut form of haemoglobin
87
Characteristics of sickle cells?
Sickle shaped
Can lead to blood vessel occlusion
Lifespan of 20 days
88
Sickle cells have a life span of?
20 days
89
Which genotype protects you from malaria with regards to sickle cell?
Homozygous for sickle cell mutation
| Heterozygous for the sickle cell mutation
90
What is the issue with being homozygous for sickle cell?
Fitness cost
| Die of sickle cell
91
As the heterozygote has an advantage and is being selected for this can be known as?
Heterozygote advantage
| Overdominance
92
How does sickle cell protect from malaria?
- 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
What is the duffy antigen?
This is a chemokine receptor located on the surface of red blood cells
94
Duffy antigen is involved in?
Chemokine bufferring
95
The duffy antigen is a receptor for?
Plasmodium vivax and Plasmodium knowlesi
96
Duffy phenotypes?
Fy a+ b+
Fy a+ b-
Fy a- b+
Fy a- b-
97
Which genotype is most prevalent in Africa?
Duffy silent allele
| Fy a-b-
98
Which allele protects from Plasmodium vivax/knowlesi infection?
Duffy antigen silent allele
| Fy a-b-
99
Where else can duffy antigen be expressed?
Endothelial cells
| In other tissues: Brain, kidney, spleen, heart, lung
100
Duffy antigen is encoded by a gene known as?
DARC
101
Individuals homozygous recessive for the Fy silent allele are protected from?
P.vivax and P.knowlesi
102
Individuals homozygous recessive for the Fy silent allele do not express what on their red blood cells?
Duffy antigen
103
Individuals homozygous recessive for the Fy silent allele do however express duffy antigen on?
Other tissues where it is normally expressed: brain, lung, liver, kidney, spleen, endothelial cells
104
How is Duffy antigen expression repressed on red blood cells alone?
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
As Duffy negative individuals still express Duffy antigen on other cell types?
They have a normal phenotype
| There is no negative fitness cost
Parasitology
flashcards
Decks in class (17)
# Cards
-
Apicomplexan Parasites49
-
Kinetoplastid Protozoans40
-
Lecture 1 short recap16
-
Giardia AV59
-
Plasmodium AV43
-
Leishmania42
-
T.cruzi30
-
Tools to investigate parasite biology24
-
Innate Immunity59
-
Adaptive Immunity38
-
Anti-parasitic vaccines50
-
Transmission Routes88
-
Transmissible Cancer64
-
Malaria evolutionary pressure105
-
T.bruci AV49
-
Vector Biology And Genetics59
-
Insecticide resistance and management35
