When intracellular signalling goes wrong

Question 1

What do pathogens exploit?

Answer 1

Several eukaryotic signalling pathways during an infection

Question 2

What have they evolved specific effectors and toxins (virulence factors) to do?

Answer 2

Hijack host cell machinery for their own benefit

Question 3

Where is cholera secreted from?

Answer 3

Vibrio chloerae

Question 4

What are the modes of transmission of cholera and their infectious dose?

Answer 4

Water - 10^9

Food - 10^3

Question 5

What are symptons of cholera?

Answer 5

Diarrhoea
Vomiting
Muscle cramps
Acidosis
Hypovolemic shock

Question 6

What happens when cholera enters the body?

Answer 6

Colonizes the epithelial lining of the small intestine

Question 7

How many chromosomes do cholera have?

Answer 7

2

Question 8

Is cholera gram-positive or gram-negative?

Answer 8

gram-negative

Question 9

What cells secrete electrolytes into the colon, leadining to water secretion?

Answer 9

Crypt cells

Question 10

What does the cholera do when entering the golgi apparatus?

Answer 10

The alpha 1 subunit disassociates from the beta and enters into the cytosol where it affects the production of adenyl cylclase increasing cAMP

Question 11

How is the A1 subunit activated?

Answer 11

human ADP-ribosylation factors which is the addition of one or more ADP-ribose moieties to a protein

Question 12

What is the active A1 subunit bound to?

Answer 12

NAD

co-activator human ADP-robosylation factor- R6

Question 13

When cholera isnt present, how does Gas reassociate with GBy subunits?

Answer 13

GTP is hydrolyzed by Gas

Question 14

What happens when cholera is present to the arginine residue in Gas leading to it not being able to hydrolyze GTP?

Answer 14

Its irreversibly modified by the addition of an ADP-ribosyl group from NAD+
(This increases intracellular cAMP levels)

Question 15

What is pertussis also known as and what is it secreted by?

Answer 15

Whoopiing cough

Bordetella pertussis

Question 16

Is pertussis gram negative?

Answer 16

Yes

Question 17

What part of the pertussis toxin subunit recognises and binds to the carbohydrate containing receptors?

Answer 17

B pentamer

Question 18

What does active GTP-bound Ga do in pertussis toxin?

Answer 18

Inhibits adenyl cyclase (AC) activity, decreasing cAMP levels

Question 19

What does pertussis toxin do when ADP-ribolysation of the Gai-subunit occurs?

What does this lead to in the respiratory tract?

Answer 19

Locks the Gai subunit into an inactive state (GDP-bound form) which means it is unable to inhibit adenyl cyclase

Mucus build-up, coughing
Antihistamine immunity

Question 20

What di mutations in proto-oncogenes and tumour supressor genes frequently lead to?

Answer 20

Cellular transformation and cancer development

Question 21

What is an oncogene?

Answer 21

A gene that has the potential to cause cancer

Question 22

What is a photo-oncogene?

Answer 22

A normal gene that can become an oncogene due to mutations or increased expression

Question 23

What is a tumour supresor gene?

Answer 23

A gene that reduces the probability that a cell in a multicellular organism will turn into a tumour cell

Question 24

What do non-acute retroviruses not carry?

Answer 24

Oncogenes and they induce tumours more slowly

Question 25

What does the Src port-oncoprotein subunit contain?

Answer 25

SH3
SH2
Kinase

Question 26

What does the SH3 domain do in Src activation?

Answer 26

Interact with other proteins and mediate assembly of specific protein complexes, typically via binding to proline-rich peptides in their respective binding partner

Question 27

What is Noonan and tiger syndrome linked to?

Answer 27

MAPkinase signalling pathway

Question 28

What is active and inactive Ras bound to?

Answer 28

Active Ras is bound to GTP; inactive Ras is bound to GDP

Like, Ga subunits of heterotrimeric G protein complexes, active Ras can slowly hydrolyse GTP, inactivating itself

Question 29

How does Ras become activated in MAPKK signalling pathway?

Answer 29

Sos – a signalling protein that activates Ras by promoting nucleotide exchange (hence Sos is a guanine exchange factor or GEF)

Question 30

How is this activated tyrosine phosphate molecules then faciliated to allow protein-protein interactions?

Answer 30

Grb2
Is an adaptor protein that binds to tyrosine phosphorylated residues to other signalling proteins
Grb2 contains an SH2 domain as well as other domains that facilitate protein:protein interactions

Question 31

What types of cells from STAT and JAK mutations can lead to cancer or PID?

PID- Primary Immunodeficiency

Answer 31

Somatic cells- Cancer

Germ cells- PID

Question 32

What is sever combines immunodeficiency (SCID)?

Answer 32

Disease in whihc the combination of non-functional T cells and defective antibody production results in multiple symptons that leads to the failure to thrive

Question 33

Where are the mutations that are the cause of X-linked SICD?

Answer 33

The common y (gamma) chain or yc gene are the cause of X-linked SCID

Question 34

Why does SCID only really affect males?

Answer 34

Found on the X chromosome

Question 35

What is the affect on T-cells and B-cells in the absence of the gamma c receptor subunit?

Answer 35

Unable to respond to a variety of cytokines which bind to receptors that use this shared component, including IL-2

(as well as IL-4, IL-7, IL-9, IL-15 and IL-21)

Question 36

What is Job’s syndrome caused by?

Answer 36

Specific genetic mutations that both under/over stimulate immune system
Leads to harmful bacterial and fungal infections

Question 37

Mutations in what gene are a major genetic cause in Job’s syndrome? And where are these muations located?

Answer 37

STAT-3

In SH2 domain and DNA binding domain