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Immunity Week 2 > ICL 5.2: Cytokines > Flashcards

ICL 5.2: Cytokines Flashcards

1
Q

what are cytokines?

A

polypeptide hormones produced by different cells and regulating the immune system

cytokines bind to specific cell-surface receptors at very low concentrations

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2
Q

what cells do cytokines act on?

A

cytokines are short-lived and act:

  1. locally on other cell types = paracrine
  2. locally on the same cell types = autocrine
  3. systemically = endocrine
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3
Q

what is cytokine redundancy?

A

similar functions are performed by different cytokines

so like cytokines A-D can all effect the same cell and cause the same thing to happen

ex. blocking or genetically ablating one cytokine rarely has widespread or dramatic effects because other cytokines are doing the same thing

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4
Q

what is cytokine pleiotropism?

A

a single cytokine exhibits many different effects on different cell types, sometimes even on the same cell type

so for example, cytokine A can effect 4 different cell types and cause 4 different things to happen

ex. over-expression or exogenous administration of a single cytokine often has several diverse effects

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5
Q

what are the different pleiotropic functions of cytokines?

A
  1. growth
  2. maturation
  3. migration
  4. growth inhibition
  5. death
  6. protein synthesis
  7. activation
  8. differentiation
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6
Q

which cytokines are involved in the acute inflammatory response against non-bacterial and common bacterial infections?

A

TNFα and IL-6

they can have both local and systemic effects!

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7
Q

where are TNFα and TNFβ produced?

A

they’re produced mainly by macrophages

but also by a broad verity of cell types including lymphoid cells, mast cells, endothelial cells, cardiac myocytes, fibroblasts, and neuronal tissue

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8
Q

what triggers TNF release?

A

TNFα and TNFβ are released in reaction to bacterial products like lipopolysaccharides

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9
Q

what are the two types of TNF receptors?

A

type 1 = constitutively expressed on multiple tissues

type 2 = expressed only on cells of the immune system

these receptors induce pro- and anti-inflammatory and apoptotic responses

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10
Q

where are IL-1α and IL-1β produced?

A

they are produced by macrophages, monocytes and dendritic cells

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11
Q

what does IL-1 do?

A
  1. responds against infection increasing expression of adhesion molecules on endothelial cells of leukocytes
  2. increases body temperature
  3. regulates hematopoiesis
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12
Q

what are the two types of IL-1 receptors?

A

Type 1: IL-1R1 is inflammatory

Type 2: IL-1R2 is an inflammation suppressor

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13
Q

where is IL-6 produced?

A

produced by macrophages and T cells

it stimulate the immune system in response to tissue damage leading to inflammation

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14
Q

what does IL-6 do?

A
  1. it’s elevated in exercise during muscle contraction
  2. it mobilizes extracellular substrates and stimulates osteoclast formation
  3. it’s the most important mediatory of fever by locally stimulating energy mobilization
  4. inhibits TNFα and IL-1!
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15
Q

how is IL-6 anti-inflammatory?

A
  1. it inhibits TNFα and IL-1
  2. it activates IL-1 receptor antagonist IL-1Rα
  3. it activates IL-10
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16
Q

when is IL-6 produced?

A

it’s secreted by macrophages in response to pathogen associated molecular patterns (PAMPs)

these PAMPs bind to toll-like receptors stimulating innate immune system

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17
Q

what are the two IL-6 receptors?

A

IL-6Ra

gp130

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18
Q

what are the local effects of TNFα/β?

A

TNFα/β are produced by activated macrophages in response to microbes like LPS on gram negative bacteria or viruses

they cause an acute inflammation response by recruiting neutrophils and macrophages

they do this by stimulating endothelial cells to produce adhesion molecules and chemokine that are chemotactic

-

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19
Q

what are the systemic effects of TNFα/β?

A

TNFα/β act on the:

  • hypothalamus = fever
  • pituitary gland
  • fibroblasts
  • endothelial cells
  • on tissue repair
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20
Q

what are the local effects of IL-1?

A

it’s an inflammatory cytokine produced by activated macrophages

has effects similar to TNF-α

protects against bacterial infections

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21
Q

what are the systemic effects of IL-1?

A

acts on:

  • fibroblasts
  • endothelial cells
  • BM
  • tissue repair
  • hypothalamus = fever
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22
Q

what are the local effects of IL-6?

A

IL-6 is an inflammatory cytokine with high range of function

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23
Q

what are the systemic effects of IL-6?

A

regulates B cell differentiation, hepatocytes, neuronal precursors, mesangial cells, osteoclasts, and other cell types

acts on hypothalamus = fever

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24
Q

which cytokines participate in the systemic acute phase response?

A

TNF

IL-1

IL-6

they effect the hypothalamus –> releases CRH –> effects pituitary –> releases ACTH –> effects adrenals –> release glucocorticosteroids –> effects liver –> releases acute phase proteins

they also active B and T cells, stimulate neutrophils and macrophages to do phagocytosis and stimulate fibroblasts and other cells

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25
what therapy is being used for rheumatoid arthritis?
anti-TNFα antibodies TNFα causes abnormally high production of pro-inflammatory cytokines IL-1, GM-CSF, and IL-6 so if you make antibodies against TNFα, it will inhibit the production of IL-1, GM-CSF, IL-6, and chemokines
26
what's the issue of treating rheumatoid arthritis with anti-TNFα antibodies?
since you're decreasing cytokine activity, you're increasing their susceptibility to infections so you have to be checking them all the time for chronic infections
27
what are examples of inflammatory bowel disease?
Crohn's ulcerates colitis
28
what causes inflammatory bowel disease?
deregulation of the adaptive immune response leading to exceeding production of pro-inflammatory cytokines = TNFα, IL-6, IL-1
29
what is infliximab?
a monoclonal antibody against TNFα it's effective for treating inflammatory bowel disease
30
which interferons are type I interferons?
IFNα IFNβ
31
where do type I interferons come from?
IFNα and IFNβ are secreted by many cells including lymphocytes, macrophages, fibroblasts, endothelial cells, osteoblasts and other cells
32
what do type I interferons do?
type I IFN = IFNα and IFNβ they stimulate macrophages and NK cells for anti-viral activity and are also active against tumors
33
what does IFNα do?
acts as a pyrogenic factor by altering activity of thermosensitive neurons in hypothalamus causing fever it also binds opioid receptors releasing prostoglandin E2
34
which interferon is a type II interferon?
IFNγ
35
where do type II interferons come from?
IFNγ is produced by: - T cells**: T helper 1 and T cytotoxic cells - dendritic cells - NK cells
36
what does IFNγ do?
it has potent anti-viral activity, immunoregulatory and anti-tumor properties: 1. increases antigen presentation by macophages 2. activates lysosome activity in macrophages 3. suppresses T helper 2 cell activity 4. promotes adhesion prior to cell migration 5. promotes NK activity
37
what are the receptors for the different IFNs?
IFNα and IFNβ bind to IFNAR1/IFNAR2 receptors IFNγ binds to IFNGR receptors IFNAR1/IFNAR2 is expressed on multiple immune and non-immune cells IFNGR is expressed only on immune cells!!!
38
what do IFNα and IFNβ do?
they inhibit viral replication in cells they increase expression of class I MHC molecules on cells facilitating killing by Tc cells they activate NK cells
39
what does IFNγ do?
- inhibits viral replication in cells - increases antigen presentation - activates lysosomes in macrophages - induces class II MHC and adhesion molecules expression - promotes NK activity
40
what is the role of IFNs in HepC?
HepC infects hepatocytes and causes degenerative changes in the liver leading to cirrhosis or liver cancer the infection is confirmed with an antibody test standard HepC treatment of INF-α-2β at a dose of three million  units three times a week for 6 months -- super strenuous and you usually have to take off work
41
what is used to treat HepC?
INF-α-2β after IFN-a-2b treatment 41% of patients normalized the serum alanine transaminase (ALT) level and 70% had histological improvement almost all responders reaching normal ALT levels lost detectable HCV-RNA by RT-PCR
42
what would an INF-γ receptor deficiency cause?
impaired ability to fight by macrophages because without INFγ, there's no macrophage activation deficiencies in IL-12 or IL-12R would cause the same symptoms
43
what do TH1 cells release?
TNFβ INFγ these activate macrophages and inhibit IL-4 which blocks TH2 activation
44
what do TH2 cells release?
IL4, IL5, and IL-13 these activate B cells and inhibit IL-12 which blocks TH1 synthesis
45
which cytokines are involved in hematopoiesis?
1. EPO 2. GM-CSF 3. SCF
46
where is EPO produced?
kidneys people on dialysis have to get EPO injections!
47
where is GM-CSF produced?
1. lungs 2. muscles 3. macrophages
48
where is M-CSF produced?
produced by multiple tissues or locally displayed by membrane it stimulates differentiation of monocytes and macrophages
49
what does G-CSF do?
it's poly functional! it stimulates stem cells to produce granulocytes = neutrophils, eosinophils and basophils** it regulates the functions of neutrophils it regulates survival, proliferation, differentiation, maturation, functional stimulation
50
what mutation can lead to CML?
valine 617 to phenylalanine in JAK2 this causes an overactive JAK2
51
what are the hematopoietic growth factors?
Thrombopoietin (TPO) Erythropoietin (EPO) Insulin growth factor 1 (IGF-1) Stem cell factor (SCF) Granulocyte colony stimulating factor (G-CSF)
52
what are the common γ chain cytokines?
**IL-2, IL-4, IL-7 also IL-9, IL-15 and IL-21
53
what are the β chain cytokines?
IL-2 IL-15
54
what does IL-2 do?
1. it's a major growth factor for T cells!! 2. it promotes the growth of B cells, NK cells, and monocytes 3. binds to IL-2Rαβγ receptor promoting cell division
55
what do CD4 Tcells differentiate into?
CD4 T cells are regulated by different cytokines to different into: - TH1 - TH2 - TH17 - Treg
56
what causes a CD4 T cell to differentiate into a TH1 cell?
IL-12
57
what do TH1 release?
IL-2 IFNγ TNF
58
what are TH1 cells involved in?
acute immune response viral defense
59
what causes a CD4 T cell to differentiate into a TH17 cell?
IL-6 TGFβ
60
what do TH17 release?
IL-17 IL-22 IFNγ
61
what are TH17 cells involved in?
bacteria defense autoimmunity
62
what causes a CD4 T cell to differentiate into a TH2 cell?
IL-4
63
what do TH2 cells secrete?
IL-4 IL-5 IL-10 IL-13
64
what are TH2 cells involved in?
antibody response parasite defense clergies like asthma in type I hypersensitivity reactions (IgE)
65
what causes a CD4 T cell to differentiate into a Treg cell?
TGFβ IL-2
66
what do Treg cells secrete?
IL-10 TGFβ
67
what are Treg cells involved in?
regulation suppression
68
what does SCID stand for?
severe combined immunodeficiency
69
what's the marker for common-gamma chain IL-2 receptor?
CD132
70
what mutations can lead to SCID?
1. mutations in: - common gamma chain - JAK3 - IL-7 receptor 2. ZAP70 mutation 3. mutations in purine degradation enzymes like ADA or PNP accumulation of nucleotide substrates are toxic to developing T cells
71
what is the function of EPO?
rescues erythroid progenitors from death used as therapy to increase the number of RBC
72
which cells produce IL-2?
NK cells TH1 cells
73
what are the receptors for IL-2?
common γ chain IL-2Rβ IL-2Rα
74
which cells secrete IL-4?
TH2 cells
75
what is the function of IL-4?
Ab production increases TH2 production decreases TH1 production
76
what are the receptors for IL-4?
common γ chain IL-4Rα
77
where is IL-7 produced?
BM stromal cells
78
what does IL-7 do?
T and B cell development memory T cells IL-7 can be used as a cancer therapy

Immunity Week 2 (12 decks)

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