Breakout Session #6

Question 1

What are three strategies employed by which pathogens change how they look so they can evade the immune system?

Answer 1

1) Gene Arrangements
2) Point Mutations
3) Genome Shuffling

Question 2

Which pathogen utilize gene rearrangements?

Answer 2

African trypanosomes

Question 3

True or False: The African Trypanosomes can undergo DNA rearrangement to change the glycoprotein expressed on the surface to evade the immune response

Answer 3

True

Question 4

During the lifecycle of trypanosome, only ___ surface glycoprotein is transcribed from the active “expression site”

Answer 4

one

Question 5

In response to ______, the trypanosome can undergo DNA rearrangement in order to bring a gene that encodes a different surface glycoprotein into the active expression site and behind an active promoter sequence

Answer 5

selective pressure

Question 6

True or False: Point mutations (due to errors via DNAP/RNAP) can be introduced into the genome during replication, leading to changes in translated protein. These changes in protein can change the epitope.

Answer 6

True

Question 7

_____: A process by which pathogens with segmented genomes are able to mix genomes with species to develop a novel species of pathogen

Answer 7

Genome shuffling

Question 8

Which virus is most closely associated with Genome Shuffling
A. E. coli
B. Trypanosomes
C. Influenza

Answer 8

C. Influenza

Question 9

The genetic shuffling causes a major change in the ____ of the virus and is called ______

Answer 9

antigenicity; antigenic shift

Question 10

Why is the immune response absent in the case of genome shuffling?

Answer 10

Body has not seen the new proteins on the surface before

Question 11

True or False: Influenza cannot undergo point mutations

Answer 11

False - they can!

Question 12

When point mutations are introduced into the genome and makes small changes to it, it is called ____

Answer 12

Antigenic Drift

Question 13

In response to antigenic drift, the immune response may be ____ due to a change in the affinity for the antigen or protective antibodies may not work any longer

Answer 13

decreased

Question 14

What are the three major outcomes of the complement pathway?

Answer 14

1) C3b acts as an opsonin
2) Increase in phagocytosis of pathogens that are bound by complement proteins
3) Formation of MAC complex by terminal pathway of complement - critical for pathogen lysis

Question 15

True or False: Pathogens have found ways to block the classical, alternative, and terminal pathways of complement in order to avoid complement-mediated destruction

Answer 15

True

Question 16

What are the three major ways that pathogens have evolved to avoid complement?

Answer 16

1) Recruitment of negative regulators/producing homologs of negative regulators
2) Inactivation of complement cascade via: enzymatic degradation
3) Modulation or direct inhibition of complement proteins by direct interaction

Question 17

Pathogens have evolved to encode homologs of negative regulators, such as ____, which dissociates C3 convertase

Answer 17

Decay Activating Factor (DAF)

Question 18

How have pathogens evolved their own enzymes that can inhibit the complement cascade?

Which pathogen almost exclusively uses this strategy?

Answer 18

By cleaving active components involved in the pathway

Bacteria

Question 19

What are two examples of targets of degradation?

Answer 19

C1a and Immunoglobulins

Question 20

Some pathogens will degrade ___ into non-functional components, so that the activation of both the ___ and ___ pathway are diminished

Answer 20

C3; classical; alternative

Question 21

How do pathogens eliminate the ability of immunoglobulins to activate C1?

Answer 21

Pathogens produce Fc receptors that bind immunoglobulins in the vicinity of the bacteria at the Fc portion, which effectively eliminates the ability of these immunoglobulins to activate C1

Question 22

There are multiple homologs that have similar activity to CD59 that inhibit the polymerization of ___ and, thus, the formation of the MAC.

What is the result of blocking the formation of MAC?

Answer 22

C9;
you will have less complement-mediated lysis of pathogen

Question 23

Pathogens have evolved to modulate the cytokine environment to promote a less-effective immune response. They primarily do this through which two mechanisms?

Answer 23

1) Production of cytokine homologs
2) Production of cytokine receptor homologs

Question 24

Which pathogen has evolved to encode cytokines that will dampen a pro-inflammatory response and promote less-effective antibody production?
A. Influenza
B. Vaccina Virus
C. Epstein-Barr Virus
D. Streptococcus Pneumoniae

Answer 24

C. Epstein-Barr Virus

Question 25

Epstein-Barr Virus encodes a homolog to the cytokine ___

Answer 25

IL-10

Question 26

What is the normal function of IL-10?

Answer 26

It acts as an anti-inflammatory cytokine that inhibits CD8+ T cells (critical in fighting EBV) and promotes the survival of its target cell (B cell)

Question 27

What is an example of a pathogen that makes a soluble form of a cytokine receptor, which then binds cytokines in this microenvironment and neutralizes their activity?
A. Influenza
B. Vaccina Virus
C. Epstein-Barr Virus
D. Streptococcus Pneumoniae

Answer 27

B. Vaccina Virus

Question 28

Vaccina Virus encodes for a soluble ____ receptor

Answer 28

IFN-gamma

Question 29

What is IFN-gamma critical for?

Answer 29

1) Activating macrophages to increase phagocytosis
2) Macrophage-mediated killing
3) Activating CD8+ T cells

Question 30

True or False: By producing a soluble IFN-gamma receptor, the Vaccina Virus neutralizes the effects of IFN gamma in an effort to minimize macrophage involvement

Answer 30

True

Question 31

True or False: Pathogens can hide from the immune system by infecting immunoprivileged sites, transforming into latency, or blocking antigen presentation

Answer 31

True

Question 32

Which organs are considered to be immunoprivileged?

Answer 32

Eyes, Brain, and Testes
- They are considered to be immunoprivileged because non-activated lymphocytes do no circulate through these organs

Question 33

___ is a pathogen strategy that aids pathogens in evading the immune response and promotes life long infections

Answer 33

Latency

Question 34

True or False: By switching from active infection to latency, the pathogen can be maintained in the host indefinitely, in many cases co-existing with the host for the rest of their life

Answer 34

True

Question 35

What is a hallmark of latent pathogens?

Answer 35

They maintain the ability to transition back to a replicative state to produce more infectious pathogens

Question 36

True or False: Pathogens have evolved to downregulate both HLA Class 1/2 expression to avoid CD8+ T cells or CD4+ T cell recognition to avoid recognition by immune system

Answer 36

True

Question 37

How does EBV stop EBV-peptides from being loaded onto HLA-1 for presentation?

Answer 37

EBNA-1 contains internal amino acids that block proteosome degradation of peptides

Question 38

How does EBV block binding of peptides to TAP 1 and 2?

Answer 38

BNFL2a

Question 39

In EBV, ____ targets HLA Class 1 for internalization and degradation

Answer 39

BILF-1

Question 40

In EBV, ___ sterically inhibits HLA II from interacting with the T cell receptor

Answer 40

gp42