When intracellular signalling goes wrong Flashcards
What do pathogens exploit?
Several eukaryotic signalling pathways during an infection
What have they evolved specific effectors and toxins (virulence factors) to do?
Hijack host cell machinery for their own benefit
Where is cholera secreted from?
Vibrio chloerae
What are the modes of transmission of cholera and their infectious dose?
Water - 10^9
Food - 10^3
What are symptons of cholera?
Diarrhoea Vomiting Muscle cramps Acidosis Hypovolemic shock
What happens when cholera enters the body?
Colonizes the epithelial lining of the small intestine
How many chromosomes do cholera have?
2
Is cholera gram-positive or gram-negative?
gram-negative
What cells secrete electrolytes into the colon, leadining to water secretion?
Crypt cells
What does the cholera do when entering the golgi apparatus?
The alpha 1 subunit disassociates from the beta and enters into the cytosol where it affects the production of adenyl cylclase increasing cAMP
How is the A1 subunit activated?
human ADP-ribosylation factors which is the addition of one or more ADP-ribose moieties to a protein
What is the active A1 subunit bound to?
NAD
co-activator human ADP-robosylation factor- R6
When cholera isnt present, how does Gas reassociate with GBy subunits?
GTP is hydrolyzed by Gas
What happens when cholera is present to the arginine residue in Gas leading to it not being able to hydrolyze GTP?
Its irreversibly modified by the addition of an ADP-ribosyl group from NAD+
(This increases intracellular cAMP levels)
What is pertussis also known as and what is it secreted by?
Whoopiing cough
Bordetella pertussis
Is pertussis gram negative?
Yes
What part of the pertussis toxin subunit recognises and binds to the carbohydrate containing receptors?
B pentamer
What does active GTP-bound Ga do in pertussis toxin?
Inhibits adenyl cyclase (AC) activity, decreasing cAMP levels
What does pertussis toxin do when ADP-ribolysation of the Gai-subunit occurs?
What does this lead to in the respiratory tract?
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
What di mutations in proto-oncogenes and tumour supressor genes frequently lead to?
Cellular transformation and cancer development
What is an oncogene?
A gene that has the potential to cause cancer
What is a photo-oncogene?
A normal gene that can become an oncogene due to mutations or increased expression
What is a tumour supresor gene?
A gene that reduces the probability that a cell in a multicellular organism will turn into a tumour cell
What do non-acute retroviruses not carry?
Oncogenes and they induce tumours more slowly
What does the Src port-oncoprotein subunit contain?
SH3
SH2
Kinase
What does the SH3 domain do in Src activation?
Interact with other proteins and mediate assembly of specific protein complexes, typically via binding to proline-rich peptides in their respective binding partner
What is Noonan and tiger syndrome linked to?
MAPkinase signalling pathway
What is active and inactive Ras bound to?
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
How does Ras become activated in MAPKK signalling pathway?
Sos – a signalling protein that activates Ras by promoting nucleotide exchange (hence Sos is a guanine exchange factor or GEF)
How is this activated tyrosine phosphate molecules then faciliated to allow protein-protein interactions?
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
What types of cells from STAT and JAK mutations can lead to cancer or PID?
PID- Primary Immunodeficiency
Somatic cells- Cancer
Germ cells- PID
What is sever combines immunodeficiency (SCID)?
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
Where are the mutations that are the cause of X-linked SICD?
The common y (gamma) chain or yc gene are the cause of X-linked SCID
Why does SCID only really affect males?
Found on the X chromosome
What is the affect on T-cells and B-cells in the absence of the gamma c receptor subunit?
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)
What is Job’s syndrome caused by?
Specific genetic mutations that both under/over stimulate immune system
Leads to harmful bacterial and fungal infections
Mutations in what gene are a major genetic cause in Job’s syndrome? And where are these muations located?
STAT-3
In SH2 domain and DNA binding domain
