W6.1

Question 1

What are Cytokines

Answer 1

small soluble proteins that regulate

the immune system’s innate and the adaptive responses to infection. (communication molecules)

Question 2

Cytokines respond to

Things that stimulate cytokines to act

Answer 2

induced in response to specific stimuli, such as bacterial lipopolysaccharides, flagellin, and other bacterial products, or signaling through the T cell or B cell receptors.

Question 3

Function of Cytokines

Answer 3

the communication molecules of the
immune system
- Individual cytokines often act in concert with others.
-The resulting network of cytokine expression
regulates leukocyte activity.
- The effects of cytokines in vivo include regulation of growth, differentiation, and gene expression by many different cell types, including leukocytes.

Question 4

Cytokine production

Answer 4

occurs through the ligation of
cell adhesion molecules or through the recognition of
foreign antigens/molecular patterns by host
lymphocytes.

Question 5

Cytokine stimulation

How cytokines affect the cells around them

Answer 5

Cytokines exert their effects through autocrine stimulation (i.e., affecting the same cell that secreted it) paracrine stimulation (i.e., affecting a target cell in close proximity), and occasionally by systemic or endocrine activities.

Question 6

Major Cytokine families

Answer 6

tumor necrosis factors (TNF), interferons (IFN), chemokines,
transforming growth factors (TGF), and
colony-stimulating factors (CSF).

Question 7

Colony stimulating factors

Answer 7

include IL-3, erythropoietin (EPO) and granulocyte (G-CSF), macrophage (M-CSF), and granulocyte-macrophage
(GM-CSF) colony-stimulating factors.

Question 8

Response to inflammatory cytokines

Answer 8

the different
colony-stimulating factors act on bone marrow cells and
promote specific colony formation for the various cell
lineages.

Question 9

Interleukins

Answer 9

unrelated cytokines that must
satisfy three criteria to be classified as interleukins:
they must have had their genes cloned, they must
be inducible in leukocytes, and their biological
activities in inflammatory processes must be
cataloged.
# IL-1 to IL-36

Question 10

Properties of cytokines

Answer 10

Many different cytokines may share properties—that
is, they activate some of the same pathways and
genes.
Pleiotropism, redundancy, synergy, antagonism

Question 11

Pleiotropism

Answer 11

Some cytokines do different things to different cell
type
One cytokine->multiple functions

Question 12

Redundancy

Answer 12

Many cytokines share receptors, some may have
overlapping effects, and some may alter the activity
of many of the same genes
Multiple cytokines->same function

Question 13

Synergy

Answer 13

Some cytokines, when working together, induce
amplified/different effects than individual cytokines
-Multiple cytokines working together

Question 14

antagonism

Answer 14

Some cytokines counteract the effects of other
cytokines
-One cytokine opposes the function of another

Question 15

Cytokines of the innate immune system

Answer 15

Type I Interferons (IFN α and IFNβ) 
Tumor necrosis factor α (TNFα) 
Interleukin 1β (IL-1β) 
Interleukin 10 (IL-10) 
Transforming growth Factor β (TGF β)
Chemokines (there are several, IL-8, Fractalkine, RANTES, SDF-1α)

Question 16

How interferons were named

Answer 16

because they interfere with viral replication.

Question 17

Type 1 interferons general characteristics

Answer 17

• the type I interferons consisting of IFN-α and IFN-β that function primarily in this manner.
  -These interferons are produced virally infected cells and by dendritic cells and induce production of proteins and pathways that can directly interfere with viral replication
  and cell division.

Question 18

Type 1 IFN are activates

Answer 18

- natural killer cells and enhances the expression of MHC class I proteins
(why does it make sense for NK cells to respond to IFN…and for IFN to increase MHCI?)
-The type I interferons are also active against certain malignancies and other inflammatory processes.

Question 19

How cytokines affect the innate immune response

Answer 19

• The main function of the innate immune response is to recruit effector cells to the area.
• Cytokines involved in triggering this response are tumor necrosis factor-α, interleukin-1,
  chemokines, and interferon α and β.

Question 20

TNF

Answer 20

were first isolated from tumor cells and were so named because they induced lysis in these cells.

Question 21

TNF-a

Answer 21

• is the most prominent member of the TNF superfamily, which consists of at least 19 different peptides that have diverse biological functions.
• TNF-α secreted by activated monocytes and
  macrophages can activate T cells through its ability to induce expression of MHC class II molecules, vascular adhesion molecules, costimulatory molecules (CD80/86, B7.1/B7.2) and chemokines
• TNF-α exists in both membrane-bound and soluble forms
  and causes vasodilation and increased vasopermeability.
• A main trigger for TNF-α production is the presence of
  lipopolysaccharide, found in gram-negative bacteria.

Question 22

IL-1 family

Answer 22

The IL-1 family consists of IL-1α, IL-1β, and IL-1RA (IL-1 receptor
antagonist).

Question 23

IL-1a and b

Answer 23

• IL-1α and IL-1β are proinflammatory cytokines produced by monocytes and macrophages.
• IL-1β is responsible for most of the systemic activity attributed to IL- 1, including fever, activation of phagocytes, and production of acute phase proteins.

Question 24

IL-1

Answer 24

• IL-1 acts as an endogenous pyrogen and induces fever in the acute phase response through its actions on the hypothalamus.
• IL-1 also induces the production of vascular cell-adhesion molecules as well as chemokines and IL-6.

Question 25

TNF-a

Answer 25

• TNF-α and IL-1 are both present in rheumatoid synovial fluids and synovial membranes of patients with rheumatoid arthritis (RA).
• TNF-α is the central mediator of pathological processes in RA and other inflammatory illnesses, such as Crohn’s disease.
• Patients with sepsis have very high levels of pro-inflammatory cytokines in their blood
• Chronic HIV disease, atherosclerosis, psoriasis, binge drinking….all have increased inflammatory cytokines
• In MANY disease states, chronically increased “inflammatory” cytokines predict mortality.