BMS106 Pathobiology - Humphreys Flashcards
What percentage of all human deaths are caused by pathogens?
25%
What is a pathogen?
An organism that causes disease
May be infectious virus, bacteria, protozoa, fungi, some may include worms and prions
The average human contains 10^13 human cells and 10^14 bacterial cells
Hey that’s pretty rad! And the microbes are often beneficial to health!
What are the 3 categories of pathogen?
Obligate pathogens - can only survive in host, usually very specific to host species
Facultative pathogens - present in the environment (reservoir) waiting for host
Opportunistic pathogens - normally benign but cause disease in compromised host
Why do pathogens make us sick?
The symptoms of the disease usually help the pathogen to spread
The pathogen kills cells I order to replicate
In some cases the symptoms appears to have no advantage or are part of the host’s response
Two closely related species can be pathogenic and harmless, often differing by only a few genes called…
Virulence genes
Virulence genes are clustered on…
Pathogenicity islands
What types of viruses can carry virulence genes and incorporate them into bacterial DNA?
Bacteriophages
There are actually hundreds of strains of Vibrio cholerae, but only strains infected with a certain bacteriophage are virulent and cause cholera. What does the bacteriophage do?
Transfers the genes that encode cholera toxin to the bacteria
How does the cholera toxin cause diarrhoea?
By dehydrating the cells of the intestine. The infected bacteria can be spread to new hosts
Many pathogens have complex life cycles. For example Fungal pathogens often show dimorphism, growing as mold at low temps in soil and switching to yeast when…
Inhaled into the warm lungs. It is then engulfed by macrophages in the yeast form
How can protozoa pathogen life cycles e complex?
They often have more than one host, for example Plasmodium falciparum which causes malaria
What is an insect that transmits a disease known as?
a vector
In order to be successful pathogens must invade our protective barriers. How is flora used as a barrier to infection?
Much of our epithelia are densely populated by bacterial and fungal flora which serve as a barrier to infection
How is mucous (e.g. in lower lung, small intestine and bladder) a barrier to infection?
It is continuously swept away or flushed and is sticky to trap stuff
How do epithelia help prevent infection?
Fit together very tightly and are held together by tight junctions which act like a gasket to make sure that pathogens can’t squeeze between cells
How do pathogens that haven’t developed a special way to enter through epithelia enter the body?
Through epithelial wounds, but breaks in epithelia are quickly recognised by white blood cells.
What are the proteins that some bacteria use to anchor themselves to epithelia called?
Adhesins
They target receptors on the host cell that normally serve other functions
What kind of secretion systems are used to inject virulence effector proteins into host cells?
Type III secretion systems
How can extracellular pathogens modify host behaviour?
Using a type III secretion system.
E.g. E. coli can make the host cell create an actin pedestal to secure them by secreting Tir
How can pathogens evade the immune system?
By hiding in a phagocytic cell
E.g. Legionnaire’s disease is caused by a bacterium that normally infects amoebae, but replicates inside macrophages that have phagocytosed it if inhaled
What are the 2 mechanisms for bacterial invasion of non-phagocytic cells and give examples of bacteria which use each mechanism?
Zipper mechanism (e.g. Listeria) Trigger mechanism (e.g. Salmonella) Both mechanisms cause actin-polymerisation, the active rearrangement of the cell
What does Listeria use the protein Listeriolysin O for?
To break down the membrane of the phagosome
What do bacterial pathogens assemble in order to push themselves into neighbouring cells?
Actin tails
What does the bacterial protein ActA do?
Initiates actin polymerisation at the tail end of Listeria
How does the bacterium Yersina pestis modify the behaviour of its flea host to suit its needs?
Blocks the flea’s digestive tract causing it to starve and bite more
Antibiotics stop bacterial growth by disrupting…
Cell processes
What are the majority of antibiotics based on?
Natural products produced by fungi or bacteria, e.g. penicillin produced by the penicillium fungus
What does MDR stand for?
Multidrug-resistant (pathogens)
What are viruses?
Fragments of nucleic acid (DNA or RNA), which encode a small number of proteins, encased in a coat protein called a capsid
What is a virus’ protein coat called?
A capsid
What is a single virus particle called?
A virion
What are the proteins encoded by viral genomes for?
Replicating the genome, packaging the genome, transporting it to host cells and modifying host cells to enhance the replication of the virus
What are the 6 main stages of the DNA virus life cycle (lytic cycle)?
Entry, uncoating, transcription & translation, genome replication, assembly of progeny, exit
What does the lysogenic cycle involve?
Viruses integrate as DNA into the host genome for a period of quiescence or latency
How many classes of viruses are there. What are they classed in terms of?
6
Their genome type and how their mRNA (+ strand) is made
Like bacteria, what do viruses rely on the presence of in order to gain entry into the host cell?
Receptors present on the surface of the host cell
What are the 4 main virus entry strategies?
Fusion with the plasma membrane
Fusion with the membrane after endocytosis
Pore formation
Endosomal membrane disruption (DNA viruses insert DNA into nucleus directly)
DNA viruses can cause cancer. What percentage of all human cancer is caused by HPV?
6%
How can viruses lead to cancer?
Proteins produced by the viral genome upregulate DNA replication and proliferation by the host cell. Accidental integration of the virus into the basal epithelial cells can result in too much proliferation and is the first step in malignant tumour formation
What virus causing genes do papillomaviruses contain several of?
oncogenes - Viral genes (E6 and E7) bind to regulatory host proteins (Rb, p53) which control proliferation and inactivate them, releasing constraints on DNA replication
What is a retrovirus?
A retrovirus is a type of RNA virus that inserts a copy of its genome into the DNA of a host cell that it invades, thus changing the genome of that cell.