Failures of Host Defence Mechanisms

Question 1

Antigenic variation for extracellular pathogens

Answer 1

• Serotypes (bacteria):
  different versions of the same pathogen, that will share distinctive surface structures. So the surface of the pathogen can exhibit different antigens/epitopes.
• Antigenic drift (viruses):
  The viruses can mutate, and the mutations can fall in the hematogglutinin or in the extracellular epitopes. And the point mutations can alter the structure of those epitopes. And the produced antibodies are not able to neutralise them.
• Antigenic shift:
  Here there are going to be mutations, but this time there will be segments instead of point mutations, that become different from the original strain. That happens when we have an exchange between the viral strain just in different hosts. These are the ones that cause the pandemics/epidemics, for example the aries can exchange with the swine infection, and get to the humans.
• Gene rearrangements:
  An example is trypanosoma, which can cause sleeping sickness. These pathogens will have multiple versions of a protein located in the external surface. There will be only one expression site. By gene conversion, they can get the different versions to the expression site. Trypanosoma has 1000 versions of that of that protein. So the immune system will have to generate the antibodies 1000x to eliminate the pathogen. This disease can only be eliminated through medications because it will eventually affect the brain.

Question 2

Latency (viruses)

Answer 2

The virus can persist and revert.
F ex: the herpes virus will show tropism for the neurons, and they will use the nerves to jump into the neuron and get to the cell body of those neurons inside the ganglia. They will stay there latent all the time, and different environmental conditions will cause this virus to reactivate, and moving again using the nerve, it will get to the area to cause an infection in the skin. It is going to be a recurrent infection.
Another example of this will be the chickenpox, which can migrate to the sensory nerve, and stay latent in the spinal cord. It can come back another time of the life but only once, and cause shingle disease.

Question 3

Resistance

Answer 3

The immune system here is going to work, but the bacteria is still going to be resistant to it.
The bacteria will have a system that will neutralize the reactive N intermediates in the macrophages, and those will not be able to kill them completely, and there will be traces of bacteria left in the organism.

Question 4

Escape

Answer 4

F ex:
Listeria is able to attach to cells, internalize into a vacuole, where the immune system will not have access to them. At some point Listeria will get out of the vacuole, and use actin from the host as a propeller to move. Then they will move projections of the membrane of the host cells, and get to another cell. So they will move throughout the intracellular space, and that’s how they will escape the immune system recognition.

Question 5

Masking

Answer 5

F ex:
The bacteria that cause syphillis is able to coat its surface with host proteins, so the immune system will not be able to recognize the infection as foreign. But they will not kill the host because they are very difficult to create in high rates in the body.
Or another bacteria that causes lime disease. This spirochid is going to be transported to the host body from a vector, such as ticks. This will cause a rash, that can be seen directly on the skin, and it needs quick treatment, because the spirochid can move to other tissues and infect them, such as the joints and then the brain. The way it masks is by recruiting regulatory factors that will regulate the complement system immune response, but also their movement through other tissues will make it difficult to get a high immune response.

Question 6

Immunosuppression

Answer 6

The lethal toxin produced from the pathogen is able to target the innate and adaptive immunities, by preventing the activation of the macrophages and maturation of the dendritic cells.
There is also going to be a rapid growth which will be free from the immune attack.