Lecture 5: Biological agents as causes of disease Flashcards
__ of all humans deaths are caused by pathogens
1/3
pathogens are
infectious viruses, bacteria, protozoans or fungi
Many scientist would include worms and prions on this list
The average human contains __ human cells and __ microbial cells
10^13
10^14
These flora are usually distinct from pathogens
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 spread the pathogen (eg diarrhoea) or because the pathogen kills cells in order to replicate. In some cases the symptoms appear to have no advantage or are part of the host’s response.
Bacteria :
cause cholera, food poisoning, syphilis and gonorrhea
Eucaryotes:
cause malaria, thrush and athlete’s foot
Viruses:
cause AIDS, small pox and the common cold
Two closely related species can be pathogenic and harmless:
the species often differ by only a few genes called virulence genes.
Fungal pathogens often show
EXAMPLES
DIMORPHISM.
-Histoplasma capsulate:
The soil form grows as a mould, but in a warm body it switches to the yeast morphology.
Candida albicans is consumed by macrophages.
After the macrophages engulf the yeast-like the fungus responds by rapidly growing a “germ tube”.
This projection eventually pierces the macrophage from the inside, killing the attacking macrophage.
Protozoa parasites often have
more than one host
MALARIA:
Plasmodium falciparum
Gametes (haploid cells) are made in human blood - These fuse to form zygotes in the gut of the Anopheles mosquito
Biting insects are a great way to
get into a host - called vectors.
Viruses that cause dengue and yellow fever can also replicate in insect cells
much of our epithelia are densely populated by
bacterial and fungal flora which serves as a barrier to infection
epithelial cells are fit together very tightly and held together by
tight junctions, these asc like a gasket to make sue that pathogens can’t squeeze between cells
Often epithelia secret…
mucous that is continuously flushed from the lower lung, small intestine and bladder.
breaks in the epithelia are quickly recognised by
WBC
Some bacteria have P pili and use sticky proteins called _____ to anchor them to the epithelia.
ADHESINS
Adhesins have “receptors” (protein targets) on the host cell that normally serve other function (eg we can’t just get rid of the receptors to block infection).
Why breach the cell membrane?
To inject toxins or to replicate inside of the cell
Toxins are often used to kill host cells for two reasons:
- killing host cells provides nutrients
- killing white blood cells helps pathogens evade the immune system.
Many bacteria have Type ___
lll (3) secretion systems that act like syringes
E.Coli assembles a ___ to overcomes barriers
an actin pedestal to hold them in place.
Tie alone is sufficient to cause this massive rearrangement of the host cell’s morphology. (forms pinch round it almost)
bacteria___ to enter cells
bacteria hide in cells.
- Pathogens can evade the immune system by hiding in a cell.
- Legionnaire’s disease is caused by a bacterium that normally infects amoebae, Legionella pneumophila.
If inhaled, the bacteria is phagocytosed by macrophages. However, unlike most bacteria, L. pneumophila replicates inside the macrophage.
Bacteria also invade nonphagocytic cells by two methods:
Zipper mechanisms
-like velcro
Trigger mechanism:
-active rearrangement of the cell membrane
Listeria entering the cell
- L. monocytogenes secretes hemolysin, a protein that breaks down the membrane of the phagosome.
- Once in the cytoplasm, the effects of hemolysin are stopped by the PEST amino acid sequence which targets the protein for destruction (PEST = proline/glutamic acid/serine/threonine).
- L. Monocytogenes then begins to replicate within the host cell.
Listeria entering the next cell
L. monocytogenes then assemble actin tails that push them into the neighbouring cell.
ActA is a bacterial protein that is localized to the tail end and nucleates actin polymerization at this end of the cell.
Antibiotics stop bacterial growth by
disrupting cellular processes
antibiotics: cell membrane
polymyxins
antibiotics: cell wall synthesis
- Vancomycin
- penicillins
- cephalosporins
antibiotics: folic acid biosynthesis
- trimethoprim
- sulfonamides
antibiotics:
DNA gyrase
quinolones
antibiotics: RNA polymerase
rifampin
Antibiotic: Protein synthesis, 30S inhibitors
- tetracycline
- streptomycin
antibiotic: protein synthesis, 50S inhibitor
- erythromycin
- chloramphenicol
antibiotics: Addition of different side chains at the R and x positions have led to
new generations of cephalosporins that have improved activities. Most drugs are continually being tinkered with in this fashion.
pathogens modify the behaviour of the host to suit their needs:
- Yersinia pestis blocks the flea’s digestive tract causing it to starve - and bite more.
- lyssavirus sp. cause rabies - biting spreads the disease.
- Toxoplasma gondii can only complete its life cycle in cats - but it gets from cat to cat travelling by rat. Infected rats loose their fear of cats and are even attracted to cat smells!
- Cordyceps sinensis infects ants and then causes them to climb up branches and clamp on then die. The hosts body then serves as a source of nutrients while the fungus grows. Finally, the fruiting body of the fungus emerges from the insect and spreads more spores.
