Quiz 4 (Lecture 17)

Question 1

What are the three evasion strategies of pathogens?

Answer 1

1. variation in surface properties (antigenic drift & shift in influenza)
2. hide inside genome (retroviruses)
3. hide inside cells (plasmodium)

Question 2

how do pathogens suppress immune function?

Answer 2

• produce proteins that disrupt immune signals
• block intracellular defenses
• slow the recruitment of immune cells
• kill immune cells

Question 3

What are the characteristics of influenza?

Answer 3

• single-stranded RNA
• segmented genome, 8 independently replicating segments
• hemagglutinin and neuraminidase proteins on surface of virion

Question 4

How is influenza classified?

Answer 4

on basis of hemagglutinin (HA) and neuraminidase (NA)
- 3 subtypes of HA and 2 subtypes of NA are human flu
- from animals HA 5, 7, 9 and NA 7 also infect humans

Question 5

What is the purpose of hemagglutinin?

Answer 5

• predominant coat of protein and initiates an infection by binding to sialic acid on the surface of a host cell
• primary protein recognized, attacked, and remember by hosts’s immune system

Question 6

What are two ways to stay alive if you are influenza A?

Answer 6

1. find a steady supply of naive hosts that have never been exposed to your version of HA
2. alter your HA so that previously exposed hosts no longer recognize it

Question 7

What two types of changes does influenza virus undergo?

Answer 7

1. antigenic drift
2. antigenic shift

Question 8

What is antigenic drift?

Answer 8

• minor changes in hemagglutinin and neuraminidase of influenza virus
• results from mutation in the RNA segments coding for HA or NA
• immune response will no longer protect fully

Question 9

What was the lineage of influenza A from 60s through 80s?

Answer 9

The flu lineages that persisted into ’80s were not a diverse assembly of strains descended from a variety of ancestors from the late ’60s

Question 10

What allowed the surviving lineage to endure while all other lineages died out?
(hypothesis and prediction)

Answer 10

h: antigenic variation, via antigenic drift, provides a selective advantage as it allows evasion of host’s immune system
p: the surviving lineage would have a higher fraction of amino acid replacements in its antigenic sites

Question 11

What is antigenic shift?

Answer 11

• major changes in hemagglutinin and neuraminidase resulting from reassortment of gene segments involving two different influenza viruses
• “new” HA or NA proteins

Question 12

What is a consequence of antigenic shift?

Answer 12

worldwide epidemics since the entire population is susceptible to the virus

Question 13

What can flu virus do that aids in immune evasion?

Answer 13

flu viruses can swap genes

Question 14

What are examples of flu viruses swapping genes?

Answer 14

• 1968 human flu acquired its H3 gene from a bird virus
• human flu sometimes infect pigs, bird strains sometimes infect pigs, and pig strains sometimes infect human

Question 15

How do flu pandemics begin?

Answer 15

when human strains and bird strains simultaneously infect a pig, swap genes with each other and perhaps with pig strains, and later move from pigs to people

Question 16

How does listeria (or lysteria) hide inside host cells?
- causes listeriosis

Answer 16

moves from macrophage to macrophage without emerging into the extracellular environment

Question 17

How does toxoplasma gondii hide inside host cells?
- causes toxoplasmosis

Answer 17

makes a vesicle inside which it is invisible to the immune system

Question 18

How does mycobacterium hide inside host cells?
- causes leprosy

Answer 18

spreads by converting nerve cells to stem cells that then invade muscles

Question 19

Why is bacterial hiding inside host cells effective?

Answer 19

• they are not exposed to adaptive immune system circulating in blood stream
• they are not eliciting an adaptive recruitment of cells that would lead to their identification and elimination

Question 20

How do plasmodium evade immune system in vertebrates?

Answer 20

hide inside cells and varies its surface molecules

Question 21

How do plasmodium evade immune system in mosquitos?

Answer 21

coats eggs to mimic mosquito cells and immunosuppresses when necessary

Question 22

Why are RBC susceptible to infections?

Answer 22

they do not carry MHC class 1 proteins, therefore there is no immune surveillance by cytotoxic T-cells

Question 23

Where are infected RBCs cleared?

Answer 23

in the spleen, where they can be recognized b/c infection increases their rigidity

Question 24

How does plasmodium prevent RBCs being cleared?

Answer 24

plasmodium inserts PfEMP1 proteins into the surface of RBCs
- this delays passage to spleen and makes them more likely to stick to capillaries in brain (causing cerebral malaria)

Question 25

How does host respond to plasmodium changing RBCs?

Answer 25

hosts target PfEMP1
- PfEMP1 elicits antibody response

Question 26

How does plasmodium evade antibody response (attack change in RBCs)?

Answer 26

• by varying PfEMP1

Question 27

What are characteristics of PfEMP 1 that allow for variants?

Answer 27

• PfEMP 1 is coded by var genes and about 60 var genes occur throughout genome
• one var gene expressed at a time

Question 28

What is antigenic switching?

Answer 28

Involves the variation of protein expression, frequently in an on-off fashion, within different parts of a bacterial population
- immune response out of phase with parasite (lags behind)

Question 29

What are the four ways to suppress the immune system?

Answer 29

1. inhibit humoral immunity by disrupting receptors
2. inhibit inflammatory responses by disrupting cell adhesion
3. Block antigen processing by inhibiting gene expression and peptide transport
4. Immunosuppress the host with interleukin mimics

Question 30

What is an example of “1. inhibit humoral immunity by disrupting receptors”?

Answer 30

-disrupt using immuno-modulatory cysteine proteases
– cleave immunoglobulin Gs; antibodies in blood and lymph

Question 31

What is an example of “2. inhibit inflammatory responses by disrupting cell adhesion”?

Answer 31

• mycobacterium tuberculosis block the fusion of phagosomes with lysosomes
• such incomplete maturation of the phagosome maintains an environment favorable to the pathogens inside it

Question 32

What is an example of “4. Immunosuppress the host with interleukin mimics”?

Answer 32

• interleukins are molecules involved in cell signaling and regulation of immune cells