Chapter 3 part 2

Question 1

Where do viruses infect and replicate?

Answer 1

WITHIN HUMAN CELLS

Question 2

Replication of viruses requires…

Answer 2

the synthesis of viral nucleic acids

Question 3

How do structure(s) within human cells detect viruses?

Answer 3

there are sensor mechanisms in the cytoplasm of human cells which can detect viral nucleic acids.
These sensors initiate production of TYPE 1 INTERFERONS (IFN)

Question 4

What are the effects of interferons?

Answer 4

interferons interfere with viral infection, signal to neighboring cells, activate immune cells (mainly NK cells), and increase susceptibility to lymphocyte (NK) attack

Question 5

Do all cells have interferon receptors? What does this allow for?

Answer 5

YES
This creates a warning system for all surrounding cells of the infected cell to prepare

Question 6

What is the name of the receptors that bind viral RNA in the cytoplasm of the human cell?

Answer 6

RLR-RIG-1 receptors

Question 7

Are receptors for viral detection internal to the cell or membrane bound?

Answer 7

both!
RLR-RIG-1 like receptors are inside of the cytoplasm

Type 1 interferon receptors are on the surface of the cell

Question 8

Explain the function of RLR-RIG-1 like receptors

Answer 8

These receptors bind viral RNA in the cytoplasm and interact with MAVS (proteins expressed on the surface of the mitochondria. Mitochondrial Antiviral Signaling Proteins)

Then, signaling is initiated that results in the transcription of IFN-B

Question 9

Name everything that is required in order for the transcription of IFN-B to take place

Answer 9

RLR-activated IRF3

Question 10

IFN-B is a….

Answer 10

type 1 interferon (along with IFN-A)

Question 11

When interferons are produced and secreted, where do they go?

Answer 11

They act on IFN receptors of the secreting cell (autocrine) AND on neighboring cells (paracrine)

Question 12

When an interferon is secreted out of the cell and binds to an interferon receptor on the cell which secreted it, what is the effect that results?

Answer 12

The number of IFN’S secreted is increased

Question 13

Explain the process that leads to the production and secretion of Type 1 interferons (A and B)

Answer 13

When a virus replicates in the cytoplasm, it produces an uncapped RNA with a 5’-triphosphate.

RLR binds to this viral RNA which induces association of this complex with MAVS (mitochondrial antiviral signaling protein) and DIMERIZATION

dimerization initiates signaling pathways. TRAF6 binds engages on one site with MAVS that leads to the activation of IRF3

IRF3 causes the synthesis and secretion of type 1 interferons

(meanwhile underneath, NFKB is becoming activated. NFKB causes synthesis of inflammatory cytokines while IRF3 causes synthesis of type 1 interferons)

Question 14

Which is secreted 1st - IFN-a or IFN-B

Answer 14

IFN-B

Question 15

Name 3 effects of the interferon response

Answer 15

-Induces resistance to viral replication in all cells

-increase expression of ligands for NK cell receptors

-Activate NK cells to kill virus-infected cells

Question 16

Name the transcription factor that is inside of the cell that gets activated when a interferon binds to a receptor on the cell which secreted it?

Answer 16

IRF7

Question 17

Are NK cells big or small?

Answer 17

large lymphocytes

Question 18

Describe the surveillance and response of NK cells to infection

Answer 18

NK cells provide constant surveillance and a rapid response to infectio

Question 19

Where do NK cells go in response to interferons?

Answer 19

NK cells migrate into tissue in response to interferons

Question 20

WHAT ARE THE 2 DISTINCT FUNCTIONS OF NK CELLS

Answer 20

1. Kill virus infected cells
2. Activate macrophages to increase the state of inflammation

Question 21

If the function of the NK cell is to kill virus-infected cells, what is the term for it?

Answer 21

a cytotoxic NK cell

Question 22

What engulfs the cells that the NK cells are killing?

Answer 22

macrophages — that’s partly why some NK cells are messengers which activate macrophages

Question 23

Do NK cells circulate

Answer 23

YES! they have a large circulating population, similar to lymphocytes

Question 24

Name 3 ways in which cytotoxic NK cell activity is regulated and WHY these forces must exist

Answer 24

1. NK cells require cell to cell contact to kill
2. Requires cooperative binding (immunological synapse) – several signals are required before it happens
3. Inhibitory receptors must be overcome by activating receptors

Question 25

What prevents NK cells from interacting with human cells?

Answer 25

we have proteins on our cell surface. However, when the NK cell recognizes enough things to signal infection, these protein obstacles are overcome

Question 26

Explain what happens when a Type 1 interferon binds to a receptor on an NK cell

Answer 26

When a type 1 interferon binds to a receptor on an NK cell, it drives the proliferation of NK cells and the differentiation of NK cells into cytotoxic effector cells. These cytotoxic effector cells kill virus-infected cells by inducing them to undergo apoptosis. The macrophage then engulfs these dead cells

Question 27

What can you say about the connection between a cytotoxic NK cell and a viral infected cell

Answer 27

the cytotoxic NK cell recognizes enough morphological changes on the cell to overcome the proteins on the surface that block it from binding, to form a stable IMMUNOLOGICAL SYNAPSE between the 2 cells

Question 28

Cytotoxic NK cells migrate and differentiate in response to…

Answer 28

IFNa and IFNb (type 1 interferons)

Question 29

What can you say about an NK-cell synapse

Answer 29

there are MANY RECEPTOR INTERACTIONS that contribute to this immunological synapse

Question 30

Explain how an NK cell “lets go” of a cell if it is found to be healthy

Answer 30

NK cells constantly make transient contact with tissue cells. If the cell is healthy, the NK cell dissociates and continues making transient contact, “looking” for an infected cell.

If the cell is found to be infected, the adhesion between the NK cell and the infected cell is strengthened and the toxic contents are delivered to the infected cell

Question 31

NK cells express ____ receptors

Answer 31

TLR’s (TOLL-like receptors)

Question 32

Which toll like receptors can recognize single stranded viral RNA?

Answer 32

TLR7 and TLR8 homodimers

Question 33

Which toll like receptor can recognize double stranded viral RNA?

Answer 33

TLR3 homodimer

Question 34

Explain the location of toll like receptors in relation to NK cells

Answer 34

toll like receptors of NK cells are actually WITHIN the NK cell (could also be on outer membrane. if on outer membrane of the NK cell, it is recognizing BACTERIA, NOT A VIRUS), membrane bound to the endosome. The recognition portion is INSIDE of the endosome while the signaling portion sticks out into the cytoplasm.
These TLR’S recognize and bind to viral nucleic acids, resulting in IFN (interferon) production within NK cells

Question 35

Explain how TLR7 within an endosome inside of an NK cell works to produce an interferon

Answer 35

TLR7 in the endosome binds to single stranded RNA and signals via MyD88 to induce interferon gene expression (IFN-a and IFN-B)

Question 36

Explain how TLR3 within an endosome works to produce interferons

Answer 36

TLR3 within the endosome binds double stranded RNA which signals TRIF to induce interferon gene expression (IRF3 is involved as well) (IFN-B)

Question 37

What do EFFECTOR NK cells do?

Answer 37

effector NK cells produce IFN-Y (type 2) to activate macrophages which increases phagocytosis and cytokine production

Question 38

effector NK cells differentiate in response to what?

Answer 38

IL-12 (derived from macrophages)

Question 39

What does a macrophage release when it comes into contact with a virus?

Answer 39

when in contact with a virus, a macrophage secretes CXCL8 and IL-12

the NK cell and the macrophage then form a synapse where IL-12 and IL-15 activate this NK cell.

The NK cells then proliferate and differentiate into EFFECTOR NK CELLS, secreting IFN-Y

IFN-Y binds BACK TO THE RECEPTOR ON THE MACROPHAGE and induces them to increase phagocytosis and production of inflammatory cytokines

Question 40

Where in the body are dendritic cells located?

Answer 40

dendritic cells are resident in ALL BODY TISSUES

Question 41

Can dendritic cells phagocytize?

Answer 41

yes

Question 42

What do dendritic cells do if they detect a pathogen?

Answer 42

If a dendritic cell detects a pathogen, its cell surface changes shape, and it secretes cytokines to activate NK cells

Question 43

Explain the relationship between NK cells and dendritic cells

Answer 43

Dendritic cells change shape if they detect a pathogen. NK cells can detect these changes and form a strong synapse with the infected dendritic cell.
From their, the NK cell will either kill the dendritic cell or induce dendritic cell differentiation (to induce the adaptive response if the innate is not handling it)

Question 44

When NK cells are abundant and they outnumber dendritic cells, what happnes?

Answer 44

the NK cells kill the dendritic cell. It’s not needed. there are plenty of NK cells so the adaptive response doesn’t need to be induced

Question 45

What happens if NK cells are scarce and are outnumbered by dendritic cells?

Answer 45

The NK cells will drive the dendritic cells to mature into the form that initiates the adaptive response