Immunology (Test Ii) : Chapter 12 : Cytokines

Front 1

What are cytokines?

Back 1

Small secreted proteins or glycoproteins. Their are about 200 known cytokines.

Front 2

How do cytokines act on target cells?

Back 2

They act on target cells by binding specific membrane receptors and altering gene expression via 2nd messengers. Usually involves tyrosine kinase cascades.

Front 3

Name 3 activities that cytokines play a role in.

Back 3

They mediate immunity, inflammation, and hematopoiesis.

Front 4

When are cytokines produced?

Back 4

They are produced de novo (only if required) in response to an immune stimulus.

Front 5

Do cytokines have a short or long half-life? What does this mean?

Back 5

They have a short half-life. They are potent. They are active in picomL.

Front 6

Do cytokines function in innate or adaptive immunity?

Back 6

Cytokines function in innate and adaptive immunity.

Front 7

'Cytokine' is a general name. List 4, more specific, names that they may be referred to as.

Back 7

1. Lymphokine (made by lymphocytes)

2. Monokine (" " monocytes)

3. Chemokine (have chemotactic activities)

4. Interleukin (made by one leukocyte and act on other leukocytes)

Front 8

List 5 characteristics of cytokines.

Back 8

1. Pleiotropy

2. Redundancy

3. Synergy

4. Antagonism

5. Cascade induction

Front 9

What does the characteristic of pleiotropy refer to?

Back 9

Cytokines are able to act on different cell types. Receptors just need to be available.

Front 10

Cytokines display the characteristic of redundancy. Explain.

Back 10

Similar functions can be stimulated by different cytokines. So if you are lacking one another could do it.

Front 11

Cytokines display the characteristic of synergy. Explain.

Back 11

Two or more cytokines can act together.

Front 12

Cytokines display the characteristic of antagonism. Explain.

Back 12

Cytokines can cause opposing activities.

Front 13

Cytokines may be involved in cascade inductions. Explain.

Back 13

One cytokine can stimulate its target cells to make other cytokine by signaling cascades.

Front 14

Describe the autocrine action of cytokines?

Back 14

When a cell makes both cytokines and receptors for those cytokines.

Front 15

Describe the paracrine action of cytokines?

Back 15

When cells produce cytokines that target nearby cells.

Front 16

Describe the endocrine action of cytokines?

Back 16

When Th produce cytokines that are transported into the blood stream and targets distance cells (like hormones).

Front 17

List the principal producers of cytokines.

Back 17

Th cells, macrophages, and dendritic cells.

Front 18

How many proteins have cytokine activity?

Back 18

More than 200 proteins have cytokine activity.

Front 19

What do most cytokines stimulate?

Back 19

Most stimulate immune cell proliferation and differentiation. (This is not the only effects that they may have, such as their role in cell death)

Front 20

Do cytokines typically act alone?

Back 20

No, they tend to act together. They rarely act alone. Target cells are exposed to a milieu containing a mix of cytokines.

Front 21

Cytokine roles are ? and ?. They are required for the ? response.

Back 21

Cytokine roles are varied and wide. They are required for the immune response.

Front 22

Cytokines promote activation, differentiation, and proliferation. They also play a role in the cell death of what cells?

Back 22

Of T cells, B cells, macrophages, dendritic cells, NK cells, and other leukocytes.

Front 23

List the 4 cytokine families.

Back 23

1. Hematopoietin

2. Interferon

3. Chemokine

4. Tumor necrosis factor

Front 24

List the five cytokine RECEPTOR families. What varies between them?

Back 24

1. Ig superfamily

2. Class I (hematopoietin)

3. Class II (Interferon)

4. TNF

5. Chemokine (very different from rest)

Front 25

List 3 Ig superfamily receptors.

Back 25

1. IL-1R (Type 1)

2. IL-1R (Type 2)

3. IL-18

Front 26

IL-1R (type 1) of the Ig superfamily receptors are expressed on what cells?

Back 26

They are expressed on many cell types.

Front 27

IL-1R (type 2) of the Ig superfamily receptors are expressed on what cells?

Back 27

They are expressed on B-cells.

Front 28

IL-18 or the Ig Superfamily Receptors is related to what? Explain. What is this an example of?

Back 28

IL-18 is related to IL-1 structurally. It has similar function and uses the same receptor family. This is an example of redundancy.

Front 29

Describe the overall general characteristics of the Ig superfamily group of receptors.

Back 29

It is a large extracellular motif held together by disulfide bonds (one of these are transmembrane).

Front 30

List 4 ligands associated with the Ig superfamily receptors?

Back 30

1. IL-1

2. M-CSF

3. C-Kit

4. IL-18

Front 31

The Class I (Hematopoietin) cytokine receptor family is comprised of dimers or trimers?

Back 31

They are composed of either one.

Front 32

Which of the cytokine receptor families is the best characterized?

Back 32

Class I (hematopoietin) receptors.

Front 33

How many subunits do the Class I (hematopoietin) receptors have? List them.

Back 33

2 subunits

1. Cytokine specific subunits

2. Signaling transducing subunits

Front 34

Class I (hematopoietin) receptors have conserved ? sequences. They also have conserved ? and an ? domain.

Back 34

They have conserved Trp-Ser-X-Trp-Ser sequences. They also have conserved cysteines and an extracellular domain.

Front 35

If a Class I (hematopoietin) Receptor is a dimer one of the subunits is specific for ? and the other is for ?.

Back 35

One is specific for transmembrane moiety and the other one is signal transducing.

Front 36

List the ligands associated with Class I (hematopoietin) receptors.

Back 36

IL-2 thru IL-7

IL-9

IL-11 thru IL-13

IL-15

GM-CSF

G-CSF

LIF

Growth Hormone Prolactin

Front 37

The Class II (INF receptor family) has a conserved ? motif.

Back 37

The class II (interferon receptor family) has a conserved CCCC family.

Front 38

List the key ligands of the Class II (INF receptor family).

Back 38

1. IFN-alpha

2. IFN-beta

3. IFN-gamma

4. IL-10

Front 39

The TNF receptor family has how many extracellular domains?

Back 39

It has 4 extracellular domains. This is a large extracellular motif.

Front 40

List the ligands associated with the TNF receptor family?

Back 40

1. TNF-alpha

2. TNF-beta

3. CD27L

4. CD30L

5. CD40L

6. Nerve growth factor (NGF)

7. FAS

Front 41

The chemokine receptor family is structurally ? from the other families.

Back 41

The chemokine receptor family is structurally different from the other families.

Front 42

The chemokine receptor family has 7 ? ?.

Back 42

The chemokine receptor family has 7 transmembrane helices.

Front 43

The chemokine receptor family interacts with what protein that the other receptor families don't interact with?

Back 43

The chemokine receptor family interacts with G-protein.

Front 44

What is a general rule of thumb about 7 transmembrane helices?

Back 44

7 transmembrane helices usually indicate an association with G-proteins.

Front 45

The chemokine receptor family looks more like a ? receptor.

Back 45

The chemokine receptor family looks more like an acetylcholine receptor.

Front 46

Some of the ligands of the chemokine receptor family are under intense investigation for the tx of what? List them.

Back 46

Intense investigation for Asthma drugs.

IL-8

RANTES

MIP-1

Front 47

The best known cytokine receptor is ?.

Back 47

The best known cytokine receptor is IL-2R. (the 'R' stands for 'receptor')

Front 48

IL-2R plays a central role in what?

Back 48

IL-2R plays a central role in the proliferation of T-cells.

Front 49

IL-2R occurs in how many different forms? These different forms exhibit different what?

Back 49

IL-2R occurs in 3 forms exhibiting different affinities for IL-2.

Front 50

The IL-2R-alpha form of IL-2R is only expressed by what cells.

Back 50

The IL-2R-alpha form of IL-2R is only expressed by activated T-cells (TAC; CD25)

Front 51

List the steps of signal transduction by most class I and class II cytokine receptors.

Back 51

1. The receptor subunits dimerize upon the binding of a cytokine

2. Activation of JAK tyrosine kinases by phosphorylation

3. Activated JAKs phosphorylate tyrosine residues forming docking sites for STATs

4. STATs dimerize

5. Dimer acts on DNA and enhances gene transcripion.

Front 52

Which ligand is the exception, and does not signal via the JAK-STAT pathway? What does it utilize?

Back 52

IL-1. It utilizes IRAK in place of STAT. IL-1 receptor associated kinase.

Front 53

Cytokine antagonists are ?.

Back 53

Cytokine antagonists are proteins.

Front 54

List the two ways in which cytokine antagonist act.

Back 54

1. Direct binding to a cytokine receptor but fail to activate the cell

2. Direct binding to a cytokine receptor, inhibiting its activity.

Front 55

Cytokine inhibitors are found where?

Back 55

They are found in the bloodstream and extracellular fluid.

Front 56

Where do cytokine inhibitors originate from?

Back 56

They originate from the enzymatic cleavage of the extracellular domain of cytokine receptors.

Front 57

Which is the best characterized of the cytokine inhibitors? When is it released?

Back 57

sIL-2R is the best characterized ('s' stands for soluble). It is released during chronic T-cell activation.

Front 58

When is sIL-2R observed?

Back 58

It is observed in some autoimmune diseases, transplant rejections, and AIDs.

Front 59

Some ? can thwart cytokines.

Back 59

Some viruses can thwart cytokines.

Front 60

List 6 strategies that viruses may use to thwart cytokines.

Back 60

1. Cytokine homologs (mimicry of cytokines)

2. Soluble cytokine binding proteins (like competitive inh.s)

3. Homologs of cytokine receptors (mimicry)

4. Interference with intracellular signaling

5. Interference with cytokine secretion

6. Induction of cytokine inhibitors in the host cell

Front 61

Cytokine secretion is predominantly from these sources.

Back 61

Cytokines secretion is predominanlty from Th1 and Th2 cells.

Front 62

Describe the cytokines secreted by Th1 cells. What is the bottom line?

Back 62

1. Delayed type hypersensitivity

2. Activation of Tc cells

3. Production of opsonization promoting IgG Abs

BOTTOM LINE : Promotion of excessive inflammation and tissue injury

Front 63

Describe the cytokines secreted by Th2 cells. What is the bottom line?

Back 63

1. Stimulates eosinophil activation

2. Helps B-cells

3. Promotes production of IgM, IgE, noncomplement IgG

BOTTOM LINE: Supports allergic reactions

Front 64

List 5 cytokines secreted by Th1.

Back 64

1. IL-2

2. IFN-gamma

3. TNF-beta

4. GM-CSF

5. IL-3

Front 65

List 5 cytokines secreted by Th2.

Back 65

1. IL-4

2. IL-5

3. IL-10

4. IL-13

5. IL-3

Front 66

List 3 functions of cytokines?

Back 66

1. Macrophage activation

2. Delayed type hypersensitivity

3. Tc cell activation

Front 67

The cytokine ? influences the development of T-cell subtypes.

Back 67

The cytokine environment influences the development of T-cell subtypes.

Front 68

A Th2 response requires what cytokine?

Back 68

IL-4

Front 69

Th1 development requires which cytokines? Explain.

Back 69

IFN-gamma, IL-12, IL-18 are all required.

1. IFN-gamma up-regulates (helps produce) IL-12 production by macrophages and dendritic cells

2. IL-18 promotes proliferation and IFN-gamma production by TH1 cells and NK cells

Front 70

Exposure of IL-4 to ? ? ? causes them to become Th2 subtypes.

Back 70

Exposure of IL-4 to naive helper cells causes them to become Th2 subtype.

Front 71

T-cell subtype balance influences ? outcomes.

Back 71

T-cell subtype balance influences disease outcomes.

Front 72

What is leprosy caused by?

Back 72

Mycobacterium leprae. It can survive within phagosomes of macrophages.

Front 73

List two types of leprosy.

Back 73

1. Tuberculoid leprosy

2. Lepromatous leprosy

Front 74

Describe tuberculoid leprosy.

Back 74

1. Cytotoxic cell mediated immune response forms granulomas ("hard-balled pkgs", "knobby")

2. Some damage to skin and traps peripheral nerves (ie, in the face)

Front 75

Describe Lepromatous leprosy.

Back 75

1. Cell-mediated response is depressed and high levels of Ig result

2. Progresses into disseminated infection of bone and cartilage with extreme nerve and tissue damage (this is serious because there is no vascular flow in the bone and cartilage)

Front 76

Tuberculoid leprosy has a ? response with ? and high levels of ?,?,?.

Back 76

Tuberculoid leprosy has a Th1 response with delayed-type hypersensitivity and high levels of IL-2, INF-gamma, and TNF-beta.

Front 77

Lepromatous leprosy has a ? response with high levels of ?,?,?.

Back 77

Lepromatous leprosy has a Th2 response with high levels of IL-4, IL-5, and IL-10.

Front 78

IL-1 is pyrogenic, what does this mean?

Back 78

IL-1 is responsible for fevers. It effects temperature regulation of hypothalamus.

Front 79

What is septic shock?

Back 79

It is a cytokine related disease. Caused by certain gram (-) bacteria. Endotoxins bind TLRs on dendritic cells and macrophages and IL-1 and TNF-alpha are overproduced leading to septic shock. (Bacterial Superantigens)

Front 80

What is Kawasaki disease?

Back 80

It is a cytokine related disease. It affects children under the age of 5 (19:100,000); mostly of Japanese or Korean descent. It affects the skin, mouth, and lymph nodes. It is treatable if caught early. If it is not caught the disease attacks the cardiovascular system. Can lead to vasculitis and cardiac arrhytmias.

Front 81

What does the treatment for Kawasaki disease?

Back 81

It includes high dose aspirin and gamma globulin.

Front 82

List some signs and symptoms of Kawasaki disease.

Back 82

Redness in both eyes, swollen lips, swollen feet, rash, and peeling skin.

Front 83

What is the most successful of the cytokine based therapies?

Back 83

The most successful is TNF-alpha inhibitor. An example is Humira made by Abbott. It also just received FDA approval for Chron's disease.

Front 84

Are there a lot of cytokine based therapies?

Back 84

There are very few really effective ones.