Lecture 7 - Innate Immunity (Key Cells and Processes)

Question 1

What are innate lymphoid cells and natural killer cells derived from?

Answer 1

Common Lymphoid Progenitor

Question 2

How many types of ILCs are there?

Answer 2

Three

Question 3

True or False?:

ILCs and NK cells are antigen specific.

Answer 3

False

ILCs and NK cells aren’t antigen specific (but ILCs are pathogen specific).

Question 4

Where can you find ILCs?

Answer 4

ILCs tend to reside in tissues.

Question 5

Where can you find NK cells?

Answer 5

NK cells can be found in tissues or circulation.

Question 6

Why are natural killer cells called natural killer cells?

Answer 6

They are called this because they can directly kill cells.

Question 7

How are ILCs activated?

Answer 7

ILCs are activated by cytokines produced in DCs or other cells (like epithelial cells).

Question 8

What do ILCs do once activated?

Answer 8

ILCs secrete cytokines that contribute to pathogen killing.

Question 9

Pictured below is an immunofluorescent staining of mouse ilea (part of the gut). Mice were either untreated (left) or treated (right) with IL-25, a cytokine often produced during Helminth infection. What are the results and what can you conclude?

Answer 9

Results: In the IL-25 treated ilea, there is a significant presence of ILCs.

Conclusion: ILCs can migrate through the lymphatic vessels.

Question 10

How does infection increase the presence of ILC2s in the gut?

Answer 10

Infection (through IL-25) increases the expression of a key receptor on ILC2s in the gut that allows trafficking of the ILC.

Question 11

True or False?:

ILCs are solely tissue resident.

Answer 11

False

ILCs are not solely tissue resident. There is evidence of gut-lung circulation of ILC2.

Question 12

What are NK cells? What do they do?

Answer 12

NK cells are lymphoid cells with innate immune functions. They express receptors for self proteins that can be induced by infections, malignant transformations, or other stresses. Activated NK cells can kill the altered self cell (due to infection or tumour) and produce cytokines that induce adaptive responses against the altered self cell.

Question 13

What do NK cell receptors recognize?

Answer 13

MHCI or MHCI-like Molecules

Question 14

True or False?:

NK cell receptors are inhibitory.

Answer 14

False

NK cell receptors can be activating or inhibiting.

Question 15

True or False?:

NK cell receptors are germline encoded.

Answer 15

True

Question 16

Why do NK cells have inhibitory receptors?

Answer 16

NK cells have inhibitory receptors so that they do not kill normal cells. Normal cells posess MHCI, which is recognized by inhibitory receptors and inhibit the signals from activating receptors.

Question 17

What would happen in a disease context that would lead to NK cells killing self cells?

Answer 17

Altered self cells that do not trigger inhibitory NK receptors will be killed because the NK cell will be receiving only activating signals.

Question 18

How do NK cells kil target cells?

Answer 18

NK cells kill target cells by releasing granule contents that induce apoptosis.

Question 19

How can NK cells trigger apoptosis in cells with DR4 and DR5?

Answer 19

If a cell expresses DR4 and DR5, the TNF family ligand TRAIL in the NK cell can bind and activate signalling via FADD to activate caspase 8, which induces apoptosis.

Question 20

What is TNF-α? What does it do?

Answer 20

Tumour necrosis factor alpha (TNF-α) is a inflammatory cytokine secreted by macrophages. It stimulates migration of innate cells, dilated blood vessels, and increases clotting.

Question 21

How is TNF-α secreted in local infection? What does this cause?

Answer 21

In local infection, macrophages activate to secrete TNF-α in the affected tissue. This leads to an increased release of plasma proteins into tissue, increased phagocyte and lymphocyte migration into tissue, and increased platelet adhesion to blood vessel walls. This causes phagocytosis of bacteria, local occlusion, and plasma and cells to drain to local lymph nodes. In the end, this causes the removal of infection or the triggering of the adaptive immune response.

Question 22

How is TNF-α secreted in systemic infection? What does this cause?

Answer 22

In systemic infection, macrophages activated in the liver and spleen secrete TNF-α into the bloodstream. This leads to systemic edema causing decreased blood volume (that causes vessel collapse), hypoproteinemia, and neutropenia, followed by neutrophila. This causes disseminated intravascular coagulation leading to wasting and multiple organ failure (sepsis). In the end, this causes death.

Question 23

What induces the acute phase response?

Answer 23

The acute phase reponse is induced by profinlammatory cytokines (IL-1, TNF-α, and IL-6).

Question 24

What does the acute phase response consist of?

Answer 24

The acute phase response involves the increased synthesis/secretion of antimicrobial proteins (mannose-binding lectin (MBL), complement components, C-reactive protein (can opsonize bacteria and trigger classical pathway)) from the liver.

Question 25

True or False?:

Liver acute phase proteins activate other processes that help eliminate pathogens.

Answer 25

True

Question 26

What causes fever?

Answer 26

Proinflammatory cytokines IL-1, IL-6, and TNF-α signal to induce a cascade that leads to a signal to the hypothalamus to increase body temperature.

Question 27

True or False?:

There is a wide variety of proinflammatory cytokines because each infers the same effect in each tissue type it is found in. As such, a majority of proinflammatory cytokines are tissue-specific.

Answer 27

False

Inflammatory cytokines have different effects in the different tissues they act in.