Cytokines Flashcards

1
Q

What are cytokines?

A

Hormone-like, soluble mediators secreted during an immune response

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2
Q

In __________ immunity, microbial and viral products stimulate macrophages and neutrophils to produce cytokines.

A

Innate

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3
Q

In ____________ immunity, cytokines are secreted by T-cells; they function to regulate T-cell growth and differentiation, as well as regulating the effector functions of T- and B-cells.

A

Adaptive

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4
Q

True or false: cytokines play a role in haematopoiesis.

A

True

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5
Q

__________ are highly potent, effective at low concentrations, and only briefly secreted.

A

Cytokines

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6
Q

What is pleiotropism?

A

One cytokine having several targets.

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7
Q

What is redundancy?

A

Many cytokines having the same function

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8
Q

Actions may be local or systemic, with ____________ and endocrine function.

A

Autocrine

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9
Q

Name three types of cytokine receptors.

A

General cytokine receptors

Chemokine receptors

TNF receptors

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10
Q

Cytokine receptors are generally not expressed on ___________ cells.

A

Resting

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11
Q

Once bound, _________ ____________ __________ (JAK) enzymes are activated, transducing the signal to the nucleus.

A

Protein tyrosine kinase

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12
Q

JAK enzymes activate _____________ _________ called signal transducers and activators (STAT).

A

Transcription factors

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13
Q

Tumour necrosis factor α (TNF-α) is sourced from ____________ __________, T-cells, mast cells, and NK cells.

A

Activated macrophages

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14
Q

TNF-α is produced by macrophages upon ligation of ______ by toll-like receptors.

A

LPS

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15
Q

________ augments TNF-α production.

A

IFN-γ

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16
Q

TNF-α is synthesised initially as a transmembrane protein, which is then cleaved by a membrane-associated __________________, releasing a 17kD polypeptide.

A

Metalloproteinase

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17
Q

What does TNF-α stimulate macrophages to secrete?

A

IL-1

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18
Q

TNF-α Stimulates ______________ actions of neutrophils.

A

Microbicidal

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19
Q

TNF-α induces vascular endothelial cells to express adhesion molecules, called ____________.

A

Selectins

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20
Q

List three functions of TNF-α in immunity.

A

Induces chemotaxis

Induces fever, as an endogenous pyrogen, by prompting the release of prostaglandins from the hypothalamus

Stimulates hepatocytes to increase synthesis of serum proteins, such as serum amyloid A and fibrinogen (acute phase response), causing intravascular thrombosis

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21
Q

Describe four potential adverse effects of TNF-α.

A

Prolonged production causes tissue wasting, or cachexia, by suppressing appetite

Prolonged production can cause hypotension

High serum levels cause severe metabolic disturbances

High serum levels can also cause septic shock, induced in response to LPS

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22
Q

Cell sources of ___________ include endothelial cells, epithelial cells, fibroblasts, and antigen-stimulated T-cells.

A

Chemokines

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23
Q

Chemokines are induced by ____________ through TLR, TNF, and IL-1.

A

Microbes

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24
Q

Chemokines stimulate _____________ movement and migration.

A

Leucocyte

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25
Q

True or false: some chemokines are produced in response to infection, while others are constitutively produced.

A

True

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26
Q

What type of receptors do chemokines engage with?

A

G-protein-coupled receptors, with seven transmembrane domains

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27
Q

Name two chemokine receptors for HIV.

A

CCR5

CXCR4

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28
Q

List three mechanisms of immunity induced by chemokines.

A

Increase the affinity of leukocytes for the endothelium

Enhance movement of leukocytes along their chemotactic gradients, by acting on actin filaments

Chemokines are specific to the cell type (e.g., CCL2 attracts monocytes; CCL11 attracts eosinophils)

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29
Q

Chemokines recruit cells to ___________ ____________ organs.

A

Peripheral lymphoid

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30
Q

True or false: chemokines promote angiogenesis and wound healing.

A

True

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31
Q

Chemokines promote migration of ___________ and memory T-cells.

A

Effector

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32
Q

What is interleukin-12?

A

Principal cytokine in response to intracellular microbes

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33
Q

IL-12 stimulates ________ production by T-cells and NK cells.

A

IFN-γ

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34
Q

IL-12 drives differentiation of T-cells into the Th1 (IFN-γ secreting) _____________.

A

Phenotype

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35
Q

IL-12 is produced by dendritic cells and ___________ _______________.

A

Activated macrophages

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36
Q

What do Type 1 interferons do?

A

Interfere with viral replication

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37
Q

Name two Type 1 interferons.

A

IFN-α and IFN-b

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38
Q

Type 1 interferons are secreted by ___________ ____________, dendritic cells and fibroblasts (IFN-b), and virally infected cells.

A

Mononuclear phagocytes

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39
Q

Production of Type 1 interferons is induced by viral nucleic acids, which bind to ligands and induce activation of __________ ____________ ____________.

A

Interferon regulatory factor

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40
Q

Receptors TLR3, TLR7, and TLR9 recognise __________ dsRNA .

A

Viral

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41
Q

State functions of Type 1 interferons.

A

Promote immunity to intracellular microbes by

Cause cells to synthesise enzymes which interfere with viral replication, e.g., 2’,5’ oligoadenylate synthetase

Induces an anti-viral state in neighbouring healthy cells

Increases expression of MHC class I

Increases CTL activity

Promotes naïve T cell differentiation to Th1 by upregulating IL-12 receptors

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42
Q

IFN-α is used in the treatment of ____________ ____.

A

Hepatitis C

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43
Q

What is IL-10?

A

An inhibitor of activated macrophages and dendritic cells, which controls innate immunity

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44
Q

True or false: is a non-covalently linked dimer.

A

True

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45
Q

Cell sources of ________ include macrophages and T-cells, and non- lymphoid cells (keratinocytes).

A

IL-10

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46
Q

State four biologic activities of IL-10.

A

Major anti-inflammatory cytokine

Inhibits IL-12 production and in turn IFN-γ production

Inhibits expression of co-stimulators and class II MHC molecules on macrophages and dendritic cells

Epstein-Barr virus has an IL-10-like gene, important for viral evasion of immunity

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47
Q

In ____________ immunity, cytokines stimulate proliferation, differentiation, and activation of effector T- and B-cells.

A

Adaptive

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48
Q

IL-2 is produced by activated _____ ___________ ___-________.

A

CD4+ helper T-cells

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49
Q

Production of IL-2 is described as ____________.

A

Transient

50
Q

IL-2 receptor is induced on activation of naïve and memory T-cells, but is always expressed on ____________ T-cells.

A

Regulatory

51
Q

________ stimulates survival, proliferation and differentiation of T-cells.

A

IL-2

52
Q

IL-2 promotes the proliferation, differentiation and ___________ function of NK cells.

A

Cytotoxic

53
Q

IL-2 stimulates __________ production in B-cells.

A

Antibody

54
Q

__________ is a major stimulus for antibody production in B-cells.

A

IL-4

55
Q

IL-4 promotes development of ________ T-cells into Th2 phenotype (IL-4 producing).

A

Naïve

56
Q

What cell type secretes IL-4?

A

CD4+ T-cells

57
Q

In synergy with ______, IL-4 activates macrophages.

A

IL-13

58
Q

IL-4 induces arginase production, promoting _____________ _____________.

A

Collagen synthesis

59
Q

IL-4 increases _________ ___________ expression, promoting phagocytosis.

A

Mannose receptor

60
Q

IFN-γ is synonymous with _______ ___ ____________.

A

Type 2 interferon

61
Q

______ is the principal macrophage-activating cytokine, essential for immunity to intracellular microbes.

A

IFN-γ

62
Q

Describe the structure and production of IFN-γ.

A

Homodimeric

Produced by CD4+ T-cells, CD8+ T-cells, and NK cells

Produced by T-cells in response to antigen

Production enhanced by IL-12 and IL-18

63
Q

Delineate some biologic activities of IFN-γ.

A

Promotes phagocytosis in macrophages

Enhances microbicidal activities of macrophages by promoting reactive oxygen intermediates

Promotes differentiation of naïve cells to Th1 phenotype

Promotes isotype switching to IgG2a in B-cells, indirectly promoting phagocytosis

Stimulates expression of MHC class I and II molecules on APC

64
Q

List functions of cytokines that are important to health.

A

Promote the onset of appropriate cellular and humoral immunity

Kick-start inflammation

Regulate haematopoiesis

Control cell proliferation and differentiation

Regulate wound healing and tissue repair

65
Q

Briefly discuss bronchial asthma.

A

Inflammatory disease of the upper airways linked with reversible airway obstruction

Increased numbers of T-cells producing exaggerated amounts of IL-4, IL-5, and IL-13 in bronchial biopsies, and these cells are drivers of eosinophil influx and activation

Linked to stimulation of mucus production

66
Q

Discuss rheumatoid arthritis.

A

Chronic autoimmune disease presenting with stiffness, pain and synovitis of large joints

Unclear pathophysiology, linked to cross reactivity of T-cells responding to microbial antigens with a self antigen

Triggers an exaggerated cytokine response from macrophages dominated by TNF-a, IL-1, and IL-8

Results in influx of immune cells from the blood (IL-8) facilitated by increased endothelial expression of adhesion molecules, in turn which secrete cytokines damaging local synovium

67
Q

In chemokine families, how many adjacent cysteine molecules does the CC family have?

A

Two

68
Q

In chemokine families, how many separated cysteine molecules does the CXC family have?

A

Two

69
Q

In chemokine families, how many cysteine molecules does the C family have?

A

One

70
Q

What is the structure of the CX3C chemokine family members?

A

Two cysteines, separated by three amino acids

71
Q

Cytokines increase the affinity of __________ for the endothelium.

A

Leucocytes

72
Q

Cytokines enhance the movement of leucocytes along their __________ ___________ by acting on actin filaments.

A

Chemotactic gradients

73
Q

CCL2 attracts ____________.

A

Monocytes

74
Q

CCL11 attracts ____________.

A

Eosinophils

75
Q

Cytokines have an __________ effect through stimulating other cells to produce angiogenic factors.

A

Indirect

76
Q

Cytokines promote migration of ____________ and memory T-cells.

A

Effector

77
Q

Cytokines promote _____________ and wound healing.

A

Angiogenesis

78
Q

What is the structure of a T-cell receptor?

A

Composed of two polypeptide chains, alpha and beta (50 and 39 kDa, respectively)

79
Q

Each alpha and beta chain is composed of variable (V) and constant (C) regions, joined by _____________ bonds.

A

Disulphide

80
Q

___________ regions on both chains are involved in antigenic recognitions.

A

Hypervariable

81
Q

__________ hypervariable regions are found on both chains of T-cell receptors.

A

Three

82
Q

A smaller group of T-cells express the ___________ _______ TCR.

A

Gamma delta

83
Q

CD4 or CD8 ___-__________ are present with T-cell receptors.

A

Co-receptors

84
Q

Describe the CD3 complex.

A

CD3 is stably associated with the TCR

Found on all T-cells

Involved in transducing signals and signalling

Composed of g, d, and e chains are associated with a ζζ homodimer

g, d, and e chains contain an Ig-like domain
Transmembrane aspartic acid binds positive charged residues in the a and b TCR chains

Cytoplasmic domains contain a conserved sequence motif ‘immunoreceptor tyrosine based activation motif’ (ITAM)

85
Q

List two other T-cell receptor accessory molecules.

A

CD28

Leucocyte function associated antigen-1

86
Q

What are accessory molecules?

A

Several integral membrane proteins involved in functional responses to antigen presentation

87
Q

Name four accessory molecules.

A

CTLA-4

CD28

LFA-a1

CD2

88
Q

State two characteristics of accessory molecules.

A

Non-polymorphic

Bind ligands on antigen presenting cells (APCs)

89
Q

Identify four functions of T-cell accessory molecules.

A

Non-specific recognition of antigen (adhesion)

Transduce biochemical signals (costimulation)

Involved in homing

Useful identification markers on T-cell

90
Q

All mature T cells arise from naïve T-cell precursors which mature in the thymus, termed Th0; in the _____________, under appropriate stimulation, subsets of CD4+ T-cells (helper) with distinctive patterns of cytokine production develop.

A

Periphery

91
Q

Identify three major subpopulations of cytokine secretion.

A

Th1

Th2

Th17

92
Q

What do Th1 cells secrete?

A

IFN-γ

TNF-α

93
Q

______ cells arise from IFN-γ and IL-12.

A

Th1

94
Q

Microbial infection induces secretion of cytokines from ___________, and the cytokines in turn act on naïve T-cells to induce differentiation to Th1 phenotype.

A

Macrophages

95
Q

Th1 cells are characterised by expression of __-_____ __________ _________ and by production of IL-2, IFN-γ, TNF-α and lymphotoxin.

A

T-bet transcription factor

96
Q

List three ways in which Th1 cells affect the stimulation of macrophages.

A

Enhancing phagocytic capacity in bacterial infection

Promote macrophage migration and diapedesis

Promote macrophage accumulation at sites of infection

97
Q

Th1 cells stimulate T-cell _____________ and differentiation.

A

Proliferation

98
Q

Th1 cells promote production of ____________-fixing antibodies by B-cells.

A

Complement

99
Q

What is the principal function of Th1 cells?

A

Phagocyte-mediated defence against infection with intracellular microbes, with promotion of neutrophil killing activity

100
Q

What is delayed-type hypersensitivity?

A

Unique type of cell-mediated immunity

The name originated from the skin test used in the diagnosis of tuberculosis (the PPD test or the tuberculin test) and denotes cellular infiltrates causing induration and erythema at the skin test site, within 24 to 72 hours

DTH responses can be induced by vaccination or by prior infection

DTH is an example of type IV hypersensitivity

Tissue injury caused by activated Th1 cells and macrophages is known as a DTH reaction, and occurs either as collateral damage after a microbial infection (physiological), or in certain autoimmune reactions (pathological)
Infection or vaccination sensitizes the individual

DTH reaction demonstrated by secondary challenge with the same antigen
Reaction is manifested by redness and swelling which peaks after 48 hours and not at four hours, i.e., ‘delayed’

101
Q

Outline the sequence of events involved in delayed-type hypersensitivity.

A

At the local site during the DTH response, CD4+ Th1 cells respond to antigen by secreting cytokines that stimulate inflammation and activate phagocytes
Neutrophils accumulate within four hours
T-cells accumulate within 12 hours
Endothelial cells become leaky
Fibrinogen escapes and becomes fibrin
Tissue swells and becomes firm (known as induration)

102
Q

Discuss chronic delayed-type hypersensitivity reactions.

A

Occur if a Th1 response to a microbe fails to eradicate the microbe
Chronically-activated macrophages grow and develop into epithelioid cells which fuse to become multi-nucleate giant cells
Clusters of activated macrophages surround the antigen producing granulomas
Granuloma formation is characteristic of M. tuberculosis infection

Tissue fibrosis accompanies granuloma formation, and normal lung tissue is replaced

103
Q

_______ cells secrete IL-4, IL-5, IL-13, IL-10.

A

Th2

104
Q

Th2 cells arise from _______ secretion.

A

IL-4

105
Q

____________ infection and allergens induce chronic activation of cells which is independent of macrophages and is associated with IL-4 secretion; IL-4 in turn acts on naïve T-cells to induce differentiation to a Th2 phenotype.

A

Helminth

106
Q

Th2 cells are characterised by expression of _______ and by production of IL-4, -5, -9, -13 and GM-CSF.

A

GATA3

107
Q

Th2 cells stimulate ___________ activation in tissue healing and repair.

A

Macrophage

108
Q

True or false: Th2 cells contribute significantly to symptoms associated with allergic reactions.

A

True

109
Q

Th2 cells cause mast cell ________________.

A

Degranulation

110
Q

Th2 cells stimulate activation of ___________ in helminthic infection.

A

Eosinophils

111
Q

Th2 cells stimulate production of _____ anti-helminth antibodies.

A

IgE

112
Q

IgE-coated helminths are bound by _________ which destroy the helminth.

A

Eosinophils

113
Q

True or false: antibodies produced by Th2 cytokines do not promote phagocytosis or complement activation, but can neutralize some toxins.

A

True

114
Q

_______ cells secrete IL-6 and IL-17.

A

Th17

115
Q

Th17 cells arise from secretion of _______.

A

IL-23

116
Q

________ cells are characterised by expression of transcription factor retinoic acid receptor-related orphan receptor γ-t (RORγt), and by secretion of IL-17, IL-22, and GM-CSF.

A

Th17

117
Q

Th17 cells play protective roles in host defence against certain bacteria at epithelial and ___________ barriers.

A

Mucosal

118
Q

True or false: Th17 are not currently believed to be involved in controlling fungal infection.

A

False

119
Q

Dysregulated IL-17 production can result in excessive pro-inflammatory _____________ _____________ and chronic inflammation, which lead to tissue damage and autoimmunity.

A

Cytokine expression

120
Q

________ family cytokines have been linked to many autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), inflammatory bowel disease, and psoriasis.

A

IL-17