8 - Cytokines and Soluble Immune Mediators

Question 1

What are cytokines?

Answer 1

Principal mediators of communication between cells of the immune system.

Cytokines are proteins produced and secreted by different cell types.

Question 2

Cytokines and their receptors are products of _____ encoded genes.

Answer 2

Germ-line.

Question 3

What happens when a Toll-like receptor interacts with a bacterial or viral molecule?

Answer 3

The TLR signals the activation of TF NFKB pathway and transcription of additional pro-inflammatory genes.

Question 4

What cytokines are downstream of the pathogen encounter and NFKB activation?

Answer 4

Secretion of:
TNF-alpha
IL-1
IL-6

Question 5

What causes a neutrophil influx after the pathogen encounter and NFKB activation?

Answer 5

G-CSF and GM-CSF: induce proliferation in the bone marrow

IL-8: chemotactic, calls in circulating PMNs

Chemokines

Question 6

What is the function of chemokines?

Answer 6

Function in a cell-contact independent manner.

They form a gradient to which PMNs are attracted.

Question 7

What do chemokines CC, CXC, and CX3C do?

Answer 7

Secreted by macrophages, epithelial, and endothelial cells to promote the migration of PMNs and other lineages into the site of infection.

Question 8

Inconcert with TNF-alpha and IL-1, chemokines promote four stages of leukocyte extravastation. What are these stages?

Answer 8

1. Rolling
2. Integrin activation by chemokines
3. Stable adhesion
4. Migration through endothelium into ECM of tissue

Question 9

Is T cell activation cell-contact dependent or independent?

Answer 9

Cell-cell contact dependent.

Question 10

What is the function of IL-2 in T cell activation?

Answer 10

It’s a cytokine that provides autocrine, cell-contact independent pro-proliferative feedback to the Th cell producing it.

Question 11

What are the defining cytokines that cause Treg cell differentiation?

Answer 11

TGF-beta and IL-10

Question 12

What is the defining cytokine that cause Th1 cell differentiation? What does this cell type protect against?

Answer 12

IFN-gamma

Intracellular pathogens.

Question 13

What are the defining cytokines that cause Th2 cell differentiation? What does this cell protect against?

Answer 13

IL-4, IL-5, and IL-13

Parasites (helminths)

Question 14

What are the defining cytokines that cause Th17 cell differentiation? What does this cell type protect against?

Answer 14

IL-17 and IL-22

Extracellular pathogens

Question 15

What are the APC derived signals that influence the differentiation of Th cells? What is the role of each?

Answer 15

IL-12: promotes Th expression of IFN-gamma (Th1)

TGF-beta: produced by many cell types, including APCs. Promotes development of Treg cells.

IL-10: promotes Treg pathway.

Question 16

What occurs if there are no APC cytokines by Th cells?

Answer 16

It will default to a Th2 cell.

Question 17

What are the Th derived signals involved in Th cell differentiation?

Answer 17

IFN-gamma: provides autocrine signal to promote Th1 gene expression. Suppresses expression of IL-4.

TGF-beta and IL-10: autocrine signal to promote further Treg development

IL-4 and IL-5: promotes autocrime skewing towards TH2

Question 18

Th1 cells are optimal for activating ______ to kill _____ pathogens.

Answer 18

Th1 cells are optimal for activating macrophages to kill intracellular bacterial pathogens.

Question 19

Th2 cells evolved primarily to eliminate ______ pathogens. Many people have Th2 cells that are directed at _____?

Answer 19

Eukaryotic pathogens (helminths).

Many people have Th2 cells that are directed at innocuous materials such as pollen and gluten, causing allergy.

Question 20

How are B cells activated?

Answer 20

Through antigen-induced clustering of membrane Ig receptors.

Triggers signals that are transduced by signaling molecules.

Question 21

How do helper T cells activate B cells?

Answer 21

They express CD40L and secrete cytokines that activate B cells causing proliferation and differentiation.

Question 22

What are the four isotypes that B cells make and the function of each?

Answer 22

IgM: complement activation

IgG: Fc receptor dependent phagocyte responses; complement, activation

IgE: immunity against helminths; mast cell degranulation

IgA: mucosal immunity

Question 23

What is the function of FcyRI (CD64) receptors? Where are they found?

Answer 23

Bind to antibodies and activate phagocytosis.

On macrophages, neutrophils, and eosinophils.

Question 24

What is the function of FcyRIIA (CD32) receptors? Where are they found?

Answer 24

Bind antibodies and activate phagocytosis. Also play a role in cell activation.

On macrophages, neutrophils, eosinophils, and platelets.

Question 25

What is the function of FcyRIIB (CD32) receptors? Where are they found?

Answer 25

Bind antibodies and function in feedback inhibition of B cells and attenuation of inflammation. On B lymphocytes, DCs, mast cells, neutrophils, and macrophages.

Question 26

What is the function of FcyRIIIA (CD16) receptors? Where are they found?

Answer 26

Bind antibodies and function in antibody-dependent cellular cytotoxicity (ADCC). Found in NK cells.

Question 27

What is the function of FcERI receptors? Where are they found?

Answer 27

Bind antibodies and function in activation (degranulation) of mast cells and basophils. Mast cells, basophils, and eosinophils.

Question 28

In general, what happens when a microbe binds to an Fc receptor?

Answer 28

The microbe is phagocytosed and killed.

Question 29

Granulocyte degranulation is regulated by _____.

Answer 29

FCERI. IgE binds to its cognate antigen while the Fc portion of the antigen binds to the FCERI receptor.

Question 30

What three soluble signals are found in granulocyte granules? What is the function of each?

Answer 30

1. Histamine: vasoactive amine stored in mast cells and causes increased vascular permeability and contraction of bronchial and smooth muscles 2. Prostaglandin D2: activate GPCRs on smooth muscle and act as vasodilator and bronchoconstrictor, promotes PMN chemotaxis 3. Leukotriene C4: cause prolonged broncho-constriction

Question 31

What is the complement cascade pathway triggered by?

Answer 31

Binding of complement proteins to the Fc portion of the antibody on the microbial surface. Is FcR-independent.

Question 32

What is antibody directed (B cell) phagocytosis dependent on?

Answer 32

FcYRI-recognition of IgG

Question 33

What is antibody-directed cytotoxicity dependent on?

Answer 33

FcYRIIIA recognition of IgG

Question 34

Where is interferon-gamma found? What is its action?

Answer 34

NK cells and T lymphocytes Activation of macrophages and stimulates some antibody responses

Question 35

Where is Type I IFNs (alpha and beta) found? What is their action?

Answer 35

IFN-alpha is in DC cells and macrophages. IFN-beta is in fibroblasts. In all cells they cause an anti-viral state and increase class I MHC expression. Also activate NK cells.

Question 36

Where is IL-15 found? What is it's action?

Answer 36

Found in macrophages. NK cell proliferation and T cell proliferation

Question 37

Where is IL-18 found? What is its action?

Answer 37

Macrophages Causes IFN-gamma production in NK cells and T cells.