Parasite Survival Strategies and Persistent Infections

Question 1

What are the antiphagocytic strategies that help avoid the innate IR

Answer 1

• release of toxins
• prevention of opsonization
• prevention of contact
• inhibition of phagolysosome function
• escape in the cytoplasm
• resistance to killing

Question 2

How do pathogens avoid opsonization (tagging of the pathogen so that the phagocyte can engulf the pathogen by identifying the heavy chain)

Answer 2

• pathogens can secret proteins that bind to the heavy chain of the antigens (protein A, released by staph. aureus)
• allows the pathogen to be invisible to the immune system
• can also use a capsule to avoid the phagocyte if the phagocyte is able to bind to the cell surface of the pathogen

Question 3

Is the capsule usually able to be produced outside of the host?

Answer 3

No

Question 4

What can a pathogen do to protect itself from the IS if its already inside the vacuole?

Answer 4

• can have to organisms avoid fusion of the granules with the vacuole
• hydrogen peroxide is a common way of destroying a pathogen already inside of the vacuole, so if the pathogen can secrete catylases that break hydrogen peroxide into water and oxygen, it will be resistant to phagocytosis

Question 5

What organism interferes with ciliary action in order to avoid the innate immune system?

Answer 5

Bordetella pertussis

- makes the person more prone to a secondary infection

Question 6

How do bacteria avoid the complement pathway?

Answer 6

• first step of the complement pathway is activating the bacteria surface molecule - if this molecule is not activated, the complement system will not be activated
• MAC can be formed when C5a is inserted into the membrane- if an organism produces proteases that can degrade this protein in the membrane then the bacterial cell can avoid the complement system here
• can shed the complement proteins in another way to avoid the activation of the complex
• decoy proteins can be released into the medium which can bind to the complement protein and do not allow the complement pathway to continue
  (decoy proteins are proteins are the receptor site that is shed by the bacterial cell- the immune cell will bind on here to the free protein receptors floating around
• this inhibits formation of the complement system

Question 7

How do bacteria avoid the innate immune system by producing iron binding molecules?

Answer 7

neisseria species makes a protein that has a higher affinity for iron than transferrins do

• snatches iron molecules from neisseria
• if you take the gene in neisseria that binds iron, it stops the ability to cause an infection

Question 8

How do blocking interferons help the pathogen avoid the innate immune response?

Answer 8

• host cells respond to ds DNA/RNA from infecting microbes by producing INF
• some viruses are poor inducers of INF (hep B) or produce molecules that block action of INF in cells (HIV)

Question 9

How do bacteria avoid the adaptive immune response?

Answer 9

• much more challenging
• B cells can recognize any shape (capsule or coat surface), thereby opsonizing a microbe for phagocytosis
• intracellular microbes in macrophages
• if an organism can minimize damage of the host, then the adaptive IS does not kick in

Question 10

How are parasite peptides detected by T cells?

Answer 10

When they are intracellular, the parasite peptides ca be presented with MHC molecules on host cell surfaces -these are detected by T cells

Question 11

How are viruses at avoiding the immune defences?

Answer 11

• very good!
• no extensive tissue damage is better for the survival of the organism
• latent virus

Question 12

What are some common evasion strategies of the adaptive IR?

Answer 12

• hit and run (adaptive immune system takes a longer time to kick in- if the organism can get into the body and cause an infection before the adaptive IS can kick in )
• concealment of antigens
• antigenic variation
• immunosuppression

Question 13

How is rhinovirus so good at avoiding the immune system?

Answer 13

• good at avoiding the immune system by working via hit and run
• we do not even have antibodies for the virus because there is not enough time to make antibodies or develop memory cells
• rotavirus also does this

Question 14

How does concealment of antigens work?

Answer 14

The antigens can hide in the host cells at sites not exposed to circulating lymphocytes

• “molecular mimicry”
• covering microbial surface with host molecules
• antigens can hide in the host cells via prevention of Ag presentation on MHC molecules
• adenovirus protein and class 1 MHC prevent its passage to the cell surface

Question 15

Where will antigens be concealed from he adaptive IR?

Answer 15

• antigens will hide in sites of the body not exposed to circulating lymphocytes
• skin, lumen, various secretions
  (warts on the skin surface are blocked off from circulating lymph - antibodies cannot get in here)

Question 16

What binds and reduces the infectious potential of the pathogen, but does not kill it?

Answer 16

IgA antibodies

Question 17

What is the best location in a cell for a pathogen to hide from the adaptive IR?

Answer 17

• can hide best if it inserts itself into the host DNA

- can live in this DNA for as long as it wants to

Question 18

What is retroviral RNA?

Answer 18

retroviral RNA is RNA that carries reverse transcriptase

• this turns RNA into DNA, and allows the DNA to become inserted into the host DNA
• as long as the viral products are not expressed, the virus can remain here indefinitely

Question 19

What is molecular mimicry?

Answer 19

• when a microbial antigen looks like a host cell
• ex. strectococcal M protein that has an antigen that is similar to an antigen in our own heart
• these antigens can cross react with the antigens in our own heart
• multiple strep infections can cause heart damage

Question 20

How can the bacteria avoid the adaptive immune response by covering itself in host molecules?

Answer 20

• strep aureus is an example
• produces protein A that has a binding site for FC proteins in the body
• phagocytosis is driven by the identification of the Fc region of the antibody
• • if they phagocytes cannot identify the Fc region, then phagocytosis does NOT occur
• the microbe or the infected cell have Fc receptors on their surface, allowing the antibodies to attach to the antigen in an upside down fashion

Question 21

How does antigenic variation allow the pathogens to evade the immune system?

Answer 21

• changing cell surface antigens allow the cells to escape the immune system
• the change in antigens may take place in the originally infected individual, enabling the microbe to undergo renewed growth, or it may take place as the microbe passes through the host population and allows it to reinfect a given individual (influenza)

Question 22

What ate the three antigenic variation mechanisms of evading the adaptive immune response?

Answer 22

• mutation
• recombination
• gene switching

Question 23

What is a common organism that undergoes mutation as a way of evading the adaptive immune system?

Answer 23

influenza virus
rhinovirus
enteroviruses

Question 24

What genes on an influenza virus mutate?

Answer 24

hemagglutinin and neuraminidase

- Ag change makes the virus unrecognizable by B and T memory cells, even from previous influenza infections

Question 25

What is mutation of the antigens also known as?

Answer 25

Antigenic drift

Question 26

What is the difference between mutation and recombination?

Answer 26

recombination results in a bigger change in the virus
(antigenic SHIFT results in a change in a whole new virus, while antigenic DRIFT is only a small change that results in mutations)
- a whole new virus only occurs from recombination, not mutation

Question 27

Describe genetic shift (aka recombination?)

Answer 27

• sudden, dramatic change in the surface antigen- can occur when genetic material between two different viruses recombine after infecting the same host (human and avian viruses)
• this gives rise to a completely new virus now experiences int he present population
• can be the start of a pandemic

Question 28

Describe gene switching?

Answer 28

eg. African typanosome
- there are genes for 1000 different surface molecules on the pathogen - can switch one gene out for the next so that the immune system is always playing catch up
- essentially, as soon as a different antigen is being expressed (all on the same pathogen), the immune systems starting all over again and treating each antigen like its coming from a different pathogen

Question 29

How does Neisseria gonorrhoea gene switch?

Answer 29

• expresses pilli on outer membrane proteins, allowing the bacteria to attach to the urethral epithelial cells
• once established, the pill proteins may switch “off” so they’re not sticky for phagocytes
• as it moves through a population, the genetic rearrangement of the pill genes allows for people to be reinfected by gonorrhoea multiple times

Question 30

What viruses infect T cells?

Answer 30

HIV, measles

Question 31

What viruses infect B cells?

Answer 31

EBV

Question 32

What virus infects both macrophages and dendritic cells?

Answer 32

HIV

Question 33

How can pathogens interfere with the immune response as a means of evading the adaptive IS?

Answer 33

• adenovirus reduces MHC-! expression

- N. gonorrhoea and S. pneumonia produces IgA protease

Question 34

What is the importance of latent viruses and what organisms do they occur in?

Answer 34

• latent viruses can be reactivated, are associated with chronic infections (HIV -> AIDS), are associated with cancer (HBV -> liver cancer), and persist in the community

Question 35

What are some examples of latent viruses?

Answer 35

chicken pox (comes back as shingles)
cold sores- HSV-1 just lays latent in the body and causes infections when the time is right

Question 36

What is a way that bacteria can avoid the effects of antibiotics?

Answer 36

• can avoid the action of antibiotics by shutting down its metabolism and need for oxygen
• this can happen in an individual with a recurrent lung infection, for example
• they are treated by an antibiotic with no sign of bacteria after (a small portion of the bacteria had shut down their metabolism and were not breathing, so the antibiotic could not come in and kill them)
• antibiotics target the reactions that are vital for life (sense breathing bacteria, for example)

Question 37

What is the reactivation process in an individual that has a latent infection?

Answer 37

2 stages (stage A and B)
Stage A: stimulus
- HSV: sunlight, fever, hormonal shifts
Stage B: spread and replication
- travel via the sensory axon to skin and mucosal surface
- infections the epithelial tissues and form virus-rosh vesicles (cold sores)
- can also be arrested by the immune system before the lesion forms: still get an itchy, tingly sensation without a cold sore