Pathogenesis Models Flashcards
Describe the structure of Corynebacterium diphtheriae. What type of pathogen is this? (viral, bacterial, fungal, protozoan, Gram-negative, Gram positive, mycobacteria, enveloped, naked, etc)
Corynebacterium diphtheriae is usually associated with this disease diphtheria which is a very severe disease. Caused by gram positive bacteria.
Where does Corynebacterium diphtheriae colonize the human body?
They normally colonize the nose. They are also sometimes found on the skin and they do not make spores. They are aerobic bacteria.
Name the 2 virulence factors that Corynebacterium diphtheriae possesses. Explain how each is necessary to cause disease.
The pili/fimbriae allow them to attach to the cells in the human pharynx. Once they’ve attached there, they start secreting a toxin which causes the disease.
The toxin kills the cells and it triggers an immune response from the body that results in a structure called a pseudo membrane. This pseudo membrane grows, usually in the upper airway and the back of the throat, and when it grows large enough it can block the upper airway completely. (DTx- the toxin that’s produced by this disease.) So this toxin is the second virulence factor.
Which organs and tissues are damaged during a classical Corynebacterium diphtheriae infection?
The toxin that’s being produced by these bacteria attack the heart, they attack the brain and they attack the kidneys. It also attacks the cells of the throat.
What is fibro-fatty infiltration?
When the toxin starts killing the heart muscle cells, the dead cells get replaced with scar tissue–what we call fibro fatty infiltration. Where now instead of contractile pink muscle cells, we have white fibrous extracellular material and sometimes some extra fat cells, some adipocytes. And so that’s why they call that fibro fatty infiltration. And it’s a type of scar tissue.
Describe what the term AB exotoxin means in detail.
The AB part refers to that there are two functional components to the toxin. The B part means a portion of the toxin that binds human cells. The B portion is necessary for this toxin to bind the human cell like a human heart cell. And the A portion is the part that is a catalyst, an enzyme that will damage human cells. the A part of the toxin, is the part that stops protein synthesis and this results in the death of the cell. The cell dies.
Down here in this diagram, the double black line represents the plasma membrane of a human cell. Think heart cell, but it could be brain or kidneys. And on the surface of that cell is a protein.
The diphtheria toxin is symbolized by this (T-Domain- red, C-Domain- green, R-Domain -blue).
One part of the protein attaches to the protein in the human membrane. And so now the toxin has attached to the plasma membrane of a human cell. After a period of time induced endocytosis will occur and a piece of that membrane gets pulled inward. During that endocytosis process, there’s usually hydrogen ions pumped into the endosome and that triggers the protein, the toxin to change shape. The red region forms a little channel through the endosome membrane and then allows the green region, the catalytic domain, to move out of the endosome and into the cytosol of the cell. So basically this toxin can sense when it’s been pulled into an endosome because of the acid that gets pumped into the endosome. And that acid then triggers the toxin to put part of itself in the cytosol, and that portion cuts itself free and diffuses over to cellular molecules called EF 2. EF2 is a protein that human cells have. EF2 is vital for the process of translation, for protein synthesis.
The enzyme part of the toxin inactivates the protein EF 2. When EF2 has been attacked by the toxin, the EF2 cannot attach to the ribosome and the ribosome can’t make proteins. When EF2 has been attacked by the toxin, the EF2 cannot attach to the ribosome and the ribosome can’t make proteins. So what we see here in the bottom right is another way of looking at that. This is NAD. The target protein here would be EF2. An enzyme is going to take those two things and react them together and that’s going to produce a target protein with this junk attached to it. The target protein is now inactive.
How is diphtheria prevented?
Diphtheria is prevented by vaccine, a toxoid. It has reduced incidence of Diptheria in our population significantly since it was administered nation wide. However, vaccination doesn’t prevent asymptomatic carriage.
How do bacteriophages relate to the 2 diseases called diphtheria?
Corynebacterium diphtheriae is an example of a bacteria that only becomes dangerous if it carries a lysogenic bacteriophage. Remember a bacteriophage can sometimes infect a bacterial cell, and then the DNA from the bacteriophage inserts into the bacterial cell’s chromosome. This special type of bacteriophage called beta phage can bring a gene that teaches the bacterial cells how to make the toxin. If they make the toxin they cause disease.
What does diphtheria toxin do once it enters a target cell? What are its target cells?
As far as diphtheria toxin goes the cells that this binds to are mostly heart, kidney, and brain cells. It also attacks the cells of the throat. It’s not actually that good at attacking the cells of the throat, but they’re so much closer to the bacteria than the other cell types that they get a fairly high dosage of the toxin. The catalyst stops protein synthesis in a target cell.
How does the diphtheria vaccine work? What is the name for all vaccines that work in similar ways?
The way the toxoid in specific works, is the toxoid stimulates the production of antibodies in the human body and those antibodies bind to diphtheria toxin. This antibody binds to diphtheria toxin and it allows the body to then neutralize diphtheria toxin. A toxoid is a type of vaccine that’s useful for intercepting a toxin.
Any vaccine that has a D in it, usually means it has the diphtheria toxoid, like TDaP or just DT or DTP or TD.
How is the diphtheria vaccine different from an antitoxin? What is an antitoxin?
An antitoxin is antibodies against a toxin that are formed, and then injected. But a toxoid is different, a toxoid isn’t directly injecting the antibodies, it’s stimulating antibody production.
Compare and contrast cutaneous diphtheria with classical diphtheria.
Cutaneous diphtheria
C. diphtheriae- wound/skin lesion infection
Slow-healing ulcer
Toxin stays local, damage limited
Disease depends on route of exposure and site of infection
The disease that Corynebacterium diphtheriae causes is determined by its route of
exposure and its site of infection. If you breathe in the droplets, that’s your route of
exposure. If it infects your throat, it’s going to cause the classic diphtheria, which could
be deadly.
The diphtheria vaccine does not prevent people from carrying Corynebacterium diphtheriae. Why not?
Vaccination against this toxin does not prevent asymptomatic carriage.
Non-toxigenic Corynebacterium spp. causes less severe disease and is not vaccine-preventable, as diphtheria toxin is the antigen for all diphtheria vaccine formulations.
A true pathogen or strict pathogen must meet 2 criteria. State them.
Obligate parasite- typically causes disease when present in/on a human. It’s obligatory to cause disease. An obligate parasite is one that must be a parasite to survive. It must damage its host in order to live.
Specialist on humans- does not grow on other hosts
What does the term facultative parasite mean?
A facultative parasite is one that has a life cycle where it doesn’t necessarily damage its host; it may not even have a host. And so it can switch into becoming a parasite when it gets on or in a person, but outside of that specific set of circumstances, it doesn’t cause disease. And so that is an example of an opportunistic pathogen.
Define: commensal opportunist.
That pattern where you have micro flora and some anatomic site that gets displaced or overgrows to a new site, so a new place in the body, and causes disease; that pattern is called commensal opportunist. Staphylococcus epidermidis is a type of commensal opportunist.
Where is Staphylococcus epidermidis normally found? In other words, what is its reservoir?
On the skin. Dominant microflora of the skin. 90% of the skin microbes are staphylococcus epidermidis.
Describe the structure of Staphylococcus epidermidis. What type of pathogen is this? (viral, bacterial, fungal, protozoan, Gram-negative, Gram positive, mycobacteria, enveloped, naked, etc)
Staphylococci are Gram positive cocci that grow in these clusters. Staphylococcus means cluster of round cells and the staphylococci are all Gram positive, at least the genus Staphylococcus is all Gram positive. Coagulase negative staphylococci
