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Micro Unit 3 > Cytokines > Flashcards

Cytokines Flashcards

1
Q

What is a cytokine?

A

Proteins secreted by cells that mediate the functions of the immune system.

soluble proteins/glycoproteins
regulate the intensity and duration of the immune response
necessary for leukocyte activation

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2
Q

Cellular sources of cytokines

A

Lymphocytes (originally called lymphokines)
Monocytes/macrophages (originally called monokines)
All cells of innate immunity
All cells of adaptive immunity
Other cells, e.g., endothelial and epithelial cells

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3
Q

Term interleukin refers to fact that many

A

proteins are produced by one immune cell to act on neighboring cells (i.e., they work between cells)

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4
Q

Term cytokine is the preferred name because it is the most i

A

nclusive term.

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5
Q

Cytokines that attract cells are called

A

chemokines.

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6
Q

Cytokine secretion is

A

brief and self-limited

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7
Q

Cytokine action is

A

pleitropic and redundant

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8
Q

Cytokines influence

A

each other

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9
Q

Cytokines can act

A

locally and systemically

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10
Q

Cytokines initiate their actions by

A

binding to specific membrane-bound receptors.

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11
Q

Cytokine receptor ligation leads to

A

gene expression which alters cellular function.

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12
Q

Cytokines increased hours after

A

challenge.

mRNA is unstable, so expression is transient

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13
Q

Cytokines can act in

A

synergy

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14
Q

Cytokines can be

A

antagonistic to each other

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15
Q

Cytokines Primarily Involved in Innate Immunity

A

Typically these cytokines impact inflammation
Proinflammatory
TNF-α, IL-1α/β, IL-6, IL-12, IFN (as well as many others)
Anti-inflammatory
IL-10, TGF-β

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16
Q

Innate immunity Importance for immunity:

A

Activate immune cells
Recruit immune cells to site of infection
Help to activate adaptive immune response

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17
Q

TNF-α

A

The principal mediator of the acute inflammatory response to Gram-negative bacteria (as well as other infectious microbes), endotoxic shock, and chronic inflammatory conditions.

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18
Q

Many cells can make TNF-α, but

A

monocytes, macrophages, NK cells, some DC cells, and T cells are the primary sources.

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19
Q

Stimulates the recruitment of

A

neutrophils, monocytes, and activated T cells to site of infection.

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20
Q

Activated leukocytes have increased expression of

A

selectin ligands first and can have increased expression of integrins later—TNF-α can facilitate this

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21
Q

TNF-α increases the expression of

A

E-selectin and then P-selectin

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22
Q

Low concentrations of TNF-α in blood plasma (i.e., approximately 1 nM) can be

A

beneficial
Participates in cellular recruitment
Participates in activation of macrophages and T cells

23
Q

Moderate concentrations of TNF-α in blood plasma (i.e., ~10-50 nM) can have

A

systemic effects, but they are often beneficial systemic effects
Acute phase proteins are increased (see slides for IL-6)
Migration of cells out of the bone marrow is increased
Fever (and sickness) develops

24
Q

High concentrations of TNF-α (>100 nM) in blood is

A

BAD.
Reductions in muscle contractions (leads to hypotension)
Immune cells are sticky leading to blood clots in circulation
Glucose release from liver becomes depleted

25
IL-1
Two forms, IL-1α and IL-1β (only share 30% homology) Bind to the same receptor (i.e., the IL-1 receptor) Have same biological function
26
Many cells produce IL-1, but primary producers are
``` mononuclear phagoyctes (i.e., monocytes/macrophages, dendritic cells) and neutrophils Shares many of the same effects with TNF-α ```
27
IL-6
Primarily produced by macrophages and T cells (but many other cells can make it). Involved with induction of inflammatory response (can have similar effects as TNF-α and IL-1). But, primarily involved with induction of the acute phase response.
28
The Immune System Communicates with the Brain Through the Production of
Cytokines
29
IL-12
Primary mediator of innate immune response to intracellular pathogens Important for the generation of adaptive immune response that would be appropriate for intracellular pathogens (i.e., T helper cell type 1 (Th1) immunity
30
IL-12 Importance for Innate Immunity is in
Activation of Macrophages
31
IL-12 Induces the Production of
IFN-γ.
32
IFN-γ can be produced by:
NK cells, T helper cells, and Cytotoxic T cells. | Macrophages that phagocytose a pathogen can kill the pathogen when they are also exposed to IFN-γ.
33
Cytokines involved with Th1 type immunity
IFNγ (and IL-2)
34
Cytokines involved with Th2 type immunity
IL-4, IL-5, IL-13 (and IL-2)
35
IL-2
IL-2 is needed for growth, survival, and differentiation of T cells (needed for BOTH T helper cells and cytotoxic T cells). Clonal expansion is IL-2 dependent IL-2 is produced by T helper cells (a.k.a. CD4+ T cells)
36
Adaptive immunity most effective against intracellular pathogen:
T heper type 1 (Th1). Involves macrophages and cytotoxic T cells Involves IFN-γ (and IL-2)
37
Adaptive immunity most effective against extracellular pathogen:
T helper type 2 (Th2). Involves antibodies produced by B cells, mast cells, and eosinophils Involves IL-4, IL-5, IL-13 (and IL-2)
38
One function of IFN-γ is to facilitate the ability of macrophages to
kill intracellular microbes Enhance microbicidal activity Increase production of opsonizing antibodies
39
In addition, IFN-γ will: | Increase
antigen presentation (so that cytotoxic T cells can kill intracellular pathogens)—we’ll learn about this next week.
40
Th2 cytokines/immunity
Immune response primarily involved with protection against extracellular pathogens (e.g., parasites).
41
IL-4
``` It is a key Th2 cytokine. It can induce naïve Th cells to differentiate into Th2 cells (i.e., Th cells that will produce more IL-4 or IL-13 or IL-5) The primary stimulus for Ig class switching to IgE. ```
42
IL-13
Very similar to IL-4 (both functionally and structurally). Primary job is to help induce Ig isotype switching to IgE. Also stimulates mucous production in gut and lung.
43
IL-5
Primary job is in eosinophil differentiation, proliferation, and activation. Eosinophils are necessary for protection against parasites
44
IL-10 is an
inhibitory cytokine
45
IL-10 Produced by
macrophages, dendritic cells, T helper cells. Its primary function is to inhibit production of IL-12 by activated macrophages (and dendritic cells).
46
Essentially chemokines are
chemotactic cytokines. They are small, soluble proteins They work primarily in paracrine or endocrine manner There are a lot of them (over 50 identified) Chemokines make up the largest category of cytokines
47
Chemokines Primary role is to
regulate migration of cells to peripheral tissues or to lymph nodes.
48
Receptors
All have at least 1 extracellular binding domain and at least 1 intracellular signaling domain. 5 receptor families for cytokines and chemokines Type I cytokine receptor Type II cytokine receptor TNF receptor family IL-1 receptor family 7 transmembrane G-protein-coupled receptors Families are distinguished by extracellular cytokine-binding domains and intracellular signaling domains
49
Type I cytokine receptor
Receptors for IL-2, IL-4, IL-5, IL-6, IL-12, and IL-13 are in this family Signal via Jak-STAT cascades
50
Type II Cytokine Receptors
Receptors for IFN-γ and IL-10 Signals via Jak-STAT Similar to Type I except that extracellular cytokine binding domain differ
51
TNF Receptor Superfamily
Receptor for TNF-α belongs to this family (as well as many other receptors for things like growth factors and other proteins) Multiple signaling cascades can be induced, can lead to transcription factor expression OR apoptosis
52
IL-1 Receptor Family
Receptor for IL-1 belongs to this family Signaling has many similarities to the Toll-like receptors Conserved cytosolic sequence, called the Toll-like/IL-1 recptor (Tir) domain that activates IRAK. IRAK initiates the signaling cascade.
53
7 transmembrane G-protein-coupled receptors
All the chemokine receptors. 7 transmembrane receptor Signaling via G-proteins Rapid and transient signaling cascade

Micro Unit 3 (6 decks)

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