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Immunology > L5: Cytokines and Effectors > Flashcards

L5: Cytokines and Effectors Flashcards

1
Q

what enters inflammed tissue from blood stream?

A

immune cells
humoral proteins
antibodies
complement proteins
innate scavenger proteins
acute phase response proteins with AMB properties

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2
Q

why do immune cells have effector functions?

A

to bind pathogens and instruct inflammation

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3
Q

what do clotting proteins do?

A

repair
prevent spread of infection

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4
Q

what effect do cytokines, eicosanoids and histamine have on blood vessels?

A

they promote and amplify inflammation, especially vasodialation

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5
Q

what are cytokines?

A

soluble extracellular proteins that regulate innate and inflammatory reactions

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6
Q

what other names are cytokines called?

A

lymphokines, monokines and adipokines

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7
Q

describe cytokines

A

low molecular weight
pleiotropic (produced by many cells)
redundant (they have similar functions)
potent (small amounts can drive inflammation)

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8
Q

is cytokine signalling autocrine, paracrine or endocrine?

A

all of the above

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9
Q

can cytokines act as hormones?

A

yes

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10
Q

what are the 5 families of cytokines?

A

IL-1
TNF Superfamily
Hematopoietic
Interferons
Chemokines

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11
Q

what does IL-1 mean?

A

interleukin-1

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12
Q

what do IL-1 cytokines signal through?

A

immunoglobulin antibody receptor domains

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13
Q

what are the subfamilies found in IL-1 cytokine family?

A

IL-1a, IL-1b, IL-18, IL-33

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14
Q

What is a receptor antagonist for cytokine IL-1?

A

IL-1Ra

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15
Q

what is IL-1Ra antagonist useful for?

A

toning down inflammation in inflammatory disease

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16
Q

how are cytokines such as IL-1 matured?

A

they are cleaved by caspase proteases

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17
Q

what caspase is involved in inflammation?

A

caspase-1

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18
Q

what adhesion molecule on endothelium do cytokines cause upregulation of ?

A

CXCL8

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19
Q

What genes do cytokines upregulate?

A

COX2/Ptgs2 generates eicosanoids which promote inflammation

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20
Q

what does excessive IL-1beta lead to?

A

tissue damage during infection as it is driving caspase proteases
this enables infection to spread

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21
Q

what happens when cells die?

A

IL-1alpha is released
this signals IL-1 receptor on neighbouring cells
this indicates that something is wrong

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22
Q

which cytokine is a key driver of Th1 response?

A

IL-18
shapes adaptive immunity

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23
Q

which cytokine is a driver of Th2 response?

A

IL-33

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24
Q

what does TNF mean?

A

tumour necrosis factor

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25
Q

what do cytokines of the TNF Superfamily interact with?

A

kinases and intracellular complexes

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26
Q

what are too high of TNF levels associated with?

A

sepsis

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27
Q

what is recognised as an age associated DAMP?

A

TNF cytokines

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28
Q

what is the function of TNF Superfamily of cytokines?

A

early response by promoting vascular permeability
drives in flammation
drives macrophage activation (resident and recruited)
drives energy mobilisation in fat to fuel immune response

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29
Q

what cytokines are part of the Hematopoietic Family?

A

IL2, IL3, IL4, GM-CSF

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30
Q

What is the function of the cytokine Hematopoietic Family?

A

cell growth and development
regulation of leukocyte development

31
Q

give 2 examples of chemokines

A

CSCL8, CCL2

32
Q

what cytokine families trigger JAK-STAT pathway?

A

hematpoietic and chemokines and INF

33
Q

what happens when JAK-STAT pathway is activated?

A

TF causes upregulation of genes in control of anti-viral function

34
Q

what cytokine familes trigger NFkB pathway?

A

IL-1 and TNF Superfamily

35
Q

what is the function of NFkB pathway?

A

regulates innate immunity
links pathogenic signals and organises cellular resistance

36
Q

what are eicosanoids?

A

lipid mediators

37
Q

what cells synthesise eicosanoids?

A

all

38
Q

what is the function of eicosanoids?

A

regulate inflammation
drive expression of COX2 gene and Pge2 enzyme

39
Q

what drugs target COX2 gene?

A

aspirin and ibruprofen

40
Q

what does Pge2 enzyme do?

A

stimulates peripheral sensory neurons
contributing to inflammation

41
Q

why do people on anti-inflammatory medication such as ibruprofen have to take digestive drugs?

A

Pge2 has a protective function in the stomach - when knocked out it can cause indigestion

42
Q

what gene does ibruprofen inhibit expression of?

A

COX1 and COX2

43
Q

what digestion drug is recommended when taking ibruprofen?

A

proton pump inhibitors (PPIs)
they pump ibruprofen out of stomach to maintain PGE2 production in stomach and double hit COX2

44
Q

how is histamine produced?

A

from mast cells , derived from histidine

45
Q

how is histamine produced by cells other than mast cells?

A

histidine decarboxylase

46
Q

what drives activation of mast cells?

A

C3a complement protein

47
Q

how is the pre-existing innate immune system exploited?

A

igE receptors circulating with bound antigens can contact mast cell and cause degranulation of mast cell
this is an allergic response due to antigen specific response

48
Q

what receptors do mast cells express?

A

H1, H2, H3, H4

49
Q

what histamine receptor do endothelial cells express?

A

H1

50
Q

what happens when histamine binds to H1 endothelial receptor?

A

increased vadcular permeability
increased expression of adhesion molecules
increased chemokines and receptor expression
chemokine gradient forms
activation of neuronal cells: itching and pain

51
Q

what happens when IgE antibodies bind with histamine?

A

allergic response

52
Q

what is IL-6 and the acute phase response?

A

a cytokine of the IL-1 family
soluble extracellular protein
binds IL-6 receptor on liver
drives inflammation
acute phase response proteins in blood increase
they have anti micorbial opsonin functions

53
Q

what is the function of acute phase response proteins?

A

anti-microbial opsonins

54
Q

what is an opsonin, give an example

A

molecules that bind and inhibit function of things
viruses bind to host receptors
CRP binds pentraxin

55
Q

what are acute phase proteins used to measure?

A

inflammation

56
Q

what does high CRP levels in blood mean?

A

serious inflammation condition

57
Q

what cytokine drives acute phase response proteins?

A

IL-6

58
Q

What drives Th1 cell polarisation?

A

IL-12

59
Q

what drives IL-12 production?

A

infection via viral and bacterial ligands
things that require CD4 response

60
Q

what drives resolution of inflammation?

A

IL-10

61
Q

what is IL-10?

A

cytokine synthesis inhibitory factor

62
Q

what enables anti-viral containment?

A

interferons INFs

63
Q

describe Type I INFs…

A

alpha and beta
antiviral

64
Q

describe Type II INFs…

A

gamma
anti microbial

65
Q

describe Type III IFNs…

A

lambda
shares properties with Type I

66
Q

describe Type III IFNs…

A

lambda
shares properties with Type I

67
Q

what pathway do IFNs activate via receptor binding?

A

JAK-STAT

68
Q

Type I IFNs drive STAT proteins that bind what sequence?

A

INF Sensitive Response Element
(ISRE)
these produce IFN sensitive genes that are anti viral

69
Q

Type II IFNs drive STAT proteins that bind what sequence?

A

GAS sequence
drives ISG (interferon sensitive genes) involved in phagocytosis and RO species

70
Q

when is IFNs produced?

A

when DCs signal to certain lymphocytes via various cytokines, lymphocytes produce various corresponding IFNs

71
Q

what happens when DCs signals IL-12?

A

Th-1 produce IFN gamma

71
Q

what happens when DCs signals IL-12?

A

Th-1 produce IFN gamma

72
Q

are IFNs themselves antiviral?

A

no
they cause upregulation of anti-viral genes via JAK-STAT

Immunology (5 decks)

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