Immunology of viruses

Question 1

Where are immature DC’s located? What is their function there?

Answer 1

In the peripheral tissues, where they are tasked with immune surveillance

Question 2

What are the steps between DC activation and lymphocyte activation? (3)

Answer 2

1. Immature DC captures antigen in peripheral tissue
2. DC starts maturing and migrates towards the lymph node
3. Mature DC arrives in the lymph node and activates naïve Th-cells

Question 3

Which complex functions as the intracellular signaling apparatus of the TCR?

Answer 3

CD3-complex

Question 4

What is immune enhancement?

Answer 4

A second infection by a pathogen causing more severe disease than the primary infection

Question 5

What are the mechanisms of immune enhancement? (4)

Answer 5

1. Enhancing antibodies
2. Hypersensitivity responses
3. Tissue damage
4. Inflammation

Question 6

What happens when a vaccine against a virus only induces CD4+ T-cell response, and not CD8+ T-cell response?

Answer 6

No creation of virus-specific CD8+ cells, leading to a mismatch in immune response during viral infection -> secondary CD4+ response and primary CD8+ response

Leads to hypersensitivity responses

Question 7

What kind of vaccine is the measles vaccine?

Answer 7

Live attentuated vaccine

Question 8

What are the advantages of the measles vaccine that make it ideal as a vector? (4)

Answer 8

1. Safe
2. Effective
3. Inexpensive
4. Induction of life-long humoral & cellular immunity

Question 9

What are the three layers of immunity?

Answer 9

1. Physical barriers
2. Innate immunity
3. Adaptive immunity

Question 10

What are examples of physical barriers that play a role in immunity? (2)

Answer 10

1. Skin
2. Mucous membranes

Question 11

What is the approximate duration for an innate immune response to kick in?

Answer 11

~12 hours

Question 12

Which class of animalia has an adaptive immune system?

Answer 12

Vertebrates (specifically: jawed vertebrates)

Question 13

What is the main innate signaling pathway in an antiviral response?

Answer 13

Type I IFN

Question 14

What are the type I interferons?

Answer 14

IFN-α, -β, -λ, -ω

Question 15

What type of interferon is IFN-α? Is it innate or adaptive?

Answer 15

Type I, innate

Question 16

What type of interferon is IFN-β? Is it innate or adaptive?

Answer 16

Type I, innate

Question 17

What type of interferon is IFN-γ? Is it innate or adaptive?

Answer 17

Type II, adaptive

Question 18

What type of interferon is IFN-λ? Is it innate or adaptive?

Answer 18

Type I, innate

Question 19

What type of interferon is IFN-ω? Is it innate or adaptive?

Answer 19

Type I, innate

Question 20

How does the innate immune system recognize pathogens?

Answer 20

Pattern recognition receptors (PRR’s) recognize pathogen-associated molecular patterns (PAMP’s)

Question 21

What is a PAMP?

Answer 21

Pathogen-associated molecular pattern -> a pattern that is recognized by the innate immune receptors as being pathogenic

Question 22

What kind of molecules tend to be PAMP’s?

Answer 22

Structural elements that are common to broad classes of microbes and hard to mutate

Question 23

By which receptors is viral RNA sensed?

Answer 23

RLR’s/NLR’s

Question 24

What is the signal transduction pathway of RLR’s? (2)

Answer 24

1. Via RIG-I
2. Via MDA-5

Both then lead to activation of MAVS, which activates transcription factors that lead to the production of type I IFN (IFN-β)

Question 25

What is the signal transduction pathway of TLR's sensing bacterial RNA?

Answer 25

MyD88/TRIF gets activated, which activates transcription factors that lead to the production of type I IFN (IFN-β)

Question 26

Which TLR's can recognize viral genomes or proteins? (3)

Answer 26

1. TLR3 -> recognizes double-stranded DNA 2. TLR9 -> recognizes CpG DNA 3. TLR4 -> recognizes viral proteins

Question 27

What viral PAMP does TLR3 recognize?

Answer 27

dsDNA

Question 28

What viral PAMP does TLR9 recognize?

Answer 28

CpG DNA

Question 29

What viral PAMP does TLR4 recognize?

Answer 29

Viral proteins

Question 30

Which TLR's are involved in the defence against RNA-viruses? Where are they located? (3)

Answer 30

1. TLR3 2. TLR7 3. TLR9 All located within the cell -> this is where viral PAMPS are found

Question 31

Where are RLR's located? What is their main function?

Answer 31

Cytoplasm; sensing RNA

Question 32

What happens to RIG-I when it encounters RNA?

Answer 32

Change in confirmation, allowing the CARD domain to interact with MAVS -> activates transcription factors -> antiviral response

Question 33

What is required for the activation of RIG-I?

Answer 33

Ubiquitins, which have to be bound by the CARD region by TRIM25 ligase

Question 34

To what kind of receptors do IFN's bind? What do these activate?

Answer 34

JAK-STAT receptors; activate the interferon-stimulated response element (ISRE) -> contains antiviral genes

Question 35

What are additional effects of type I IFN (in addition to activation of the ISRE)? (4)

Answer 35

1. Production of cytokines 2. Induction of apoptosis 3. Activation of the adaptive immune system 4. DC maturation

Question 36

Which cytokines are typically produced in an type I IFN response?

Answer 36

1. TNF-α 2. IL-5 3. IL-6 4. IL-12

Question 37

How do viruses counteract innate immunity?

Answer 37

Through the production of antagonistic proteins

Question 38

Why is it useful to identify viral antagonistic proteins?

Answer 38

Can contribute to vaccine and thereaputic developments