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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
Q

IL-1

A

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
Q

Many cells produce IL-1, but primary producers are

A 
mononuclear phagoyctes (i.e., monocytes/macrophages, dendritic cells) and neutrophils
Shares many of the same effects with TNF-α
27
Q

IL-6

A

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
Q

The Immune System Communicates with the Brain Through the Production of

A

Cytokines

29
Q

IL-12

A

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
Q

IL-12 Importance for Innate Immunity is in

A

Activation of Macrophages

31
Q

IL-12 Induces the Production of

A

IFN-γ.

32
Q

IFN-γ can be produced by:

A

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
Q

Cytokines involved with Th1 type immunity

A

IFNγ (and IL-2)

34
Q

Cytokines involved with Th2 type immunity

A

IL-4, IL-5, IL-13 (and IL-2)

35
Q

IL-2

A

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
Q

Adaptive immunity most effective against intracellular pathogen:

A

T heper type 1 (Th1).

Involves macrophages and cytotoxic T cells
Involves IFN-γ (and IL-2)

37
Q

Adaptive immunity most effective against extracellular pathogen:

A

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
Q

One function of IFN-γ is to facilitate the ability of macrophages to

A

kill intracellular microbes

Enhance microbicidal activity
Increase production of opsonizing antibodies

39
Q

In addition, IFN-γ will:

Increase

A

antigen presentation (so that cytotoxic T cells can kill intracellular pathogens)—we’ll learn about this next week.

40
Q

Th2 cytokines/immunity

A

Immune response primarily involved with protection against extracellular pathogens (e.g., parasites).

41
Q

IL-4

A 
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
Q

IL-13

A

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
Q

IL-5

A

Primary job is in eosinophil differentiation, proliferation, and activation.
Eosinophils are necessary for protection against parasites

44
Q

IL-10 is an

A

inhibitory cytokine

45
Q

IL-10 Produced by

A

macrophages, dendritic cells, T helper cells.

Its primary function is to inhibit production of IL-12 by activated macrophages (and dendritic cells).

46
Q

Essentially chemokines are

A

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
Q

Chemokines Primary role is to

A

regulate migration of cells to peripheral tissues or to lymph nodes.

48
Q

Receptors

A

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
Q

Type I cytokine receptor

A

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
Q

Type II Cytokine Receptors

A

Receptors for IFN-γ and IL-10
Signals via Jak-STAT
Similar to Type I except that extracellular cytokine binding domain differ

51
Q

TNF Receptor Superfamily

A

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
Q

IL-1 Receptor Family

A

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
Q

7 transmembrane G-protein-coupled receptors

A

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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