chemokines (GPCR) and cytokines (Jak/Stat) Flashcards

1
Q

List the kinetics of the inflammatory response to microbial infection

A

1) Exudation
2) Neutrophils
3) Apoptosis
4) Mono Nuclear Cells (macrophages, DC)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

List the secretions that acccompany the Kinetics of the inflammatory response to microbial infection

A

1) at 30 minutes
- Histamine
- Serotonin
- Bradykinin
- Complement

2) 1hr-3hr-6hr
PGs
LTs

3) 24HR
TNF
IL-1Beta
LX

4) 24 hr- 48hr
MCP1 or CCL2
IL6

5) 48hr 
cyPGs
BAX
p53
TGF-Beta1 TRANSFORMING GROWTH FACTOR BETA-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Platelets secrete WHAT molecule that the intestines also secrete.

A

SEROTONIN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

T/F Platelets express MHCI despite not have a nucleus.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

T/F RBC do NOT express MHCI because it doesn’t have a nucleus

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Anti-inflammatory mediators examples?

A

Lipoxins (LXs)

CyPGs (cyclopentenone PG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Lipoxins and CyPGs are WHAT mediators and attenuate WHAT and Promote WHAT from the inflammatory site

A

CyPGs and LX are ANTI-INFLAMMATORY, that ATTENUTATE CELL MIGRATION and promote APOPTOSIS and CLEARANCE of LEUKOCYTES from inflammatory sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which is the umbrella term? Cytokines or Chemokines

A

Cytokines are more general

Chemokines are CHEMOattractant CYTOKINEs

Chemokines are a type of cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Chemokines are a type of cytokines T/F

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

CCL21 are highly expressed in lymph nodes at attract what receptors?

A

CCR7 Receptors found on APC and naive T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

During healthy homeostasis, CCL21 attracts and retain what cells in the Lymph NOde

A

NAIVE T cells in the LYMPH NODE (due to theri CCR7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

During INNATE immune response, CCL2 (MCP-1) attracts WHAT and WHAT to sites of injury and infection?

A

MONOCYTES and MACROPHAGES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CCL2 (MCP-1) is different from CCL21 by?

A

CCL2 attracts MONOcytes and MACROphages to sites of INJURY and INFECTION

CCL21 is expressed in LYMPH NODES and attract APC cells and NAIVE T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CCL2 is also known as

A

MCP-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

MCP-1 is also known as

A

CCL2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What chemokine attracts Monocyte and Macrophages to site of injury and infection?

A

CCL2 or MCP-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What chemokine attracts APC to Lymph Nodes via their CCR7?

A

CCL21

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

During homeostasis at the LYMPH NODE, WHAT chemokine is expressed to retain WHAT kind of cells

A

CCL21 is expressed at LN to RETAIN NAIVE T Cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Understand the since CHEMOkines interact with GPCR the same chemokine can produce (same/different) effect on cells with different GPCRs.

A

DIFFERENT

the same chemokine can bind to Gs at one cell and a Gi at a different cell, SAME chemokine different effect at different receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

T/F Chemokines are SMALL 8-10kd, SOLUBLE and thus can DIFFUSE AWAY from site of secretion.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Chemokines also efficently bind to…?

A

Extracellular Matrix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the benefit of Chemokines efficently binding to the ECM?

A

it can TETHER cells that expressing CHEMOKINE RECEPTORS to the ECM presenting CHemokine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

For Chemokines and Cytokines, which has Jak/Stat and which has GPCR

A

Chemokines/PG - GPCR

Cytokines - JAK/STAT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the cysteine residues of Alpha chemokines

A

Alpha Chemokines or CXC chemokines have an a.a between the FIRST and THIRD conserved CYTSTEIN RESIDUES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Alpha Chemokines are also known as

A

CXC chemokines

Nomenclature CXCL8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

CXC chemokines are also known as

A

Alpha Chemokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

CXC chemokines or Alpha Chemokines are targeted more to WHAT cells than to other immune cells.

A

CXC chemokines or Alpha chemokines are targeted more to NEUTROPHILS than to other immune cells

Nomenclature CXCL8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Beta Chemokines are also known as

A

CC chemokines

nomeclature CCL4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

CC chemokines are also known as

A

Beta Chemokines

Nomenclature CCL4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe the cytstein residues of Beta Chemokines

A

The first two conserved CYSTEINE residues are adjacent with no a.a. in b/w

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

CC chemokines or Beta Chemokines tend to NOT be a WHAT for WHAT CELL: NAME OF MOLECULE that specifically recruits WHAT IMMUNE CELL

A

CC chemokines tend NOTbe a CHEMOATTRACTANT to NEUTROPHILS:

EOTAXIN recruits EOSINOPHILS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What chemokine targets Neutrophils more than other immune cell

A

Alpha or CXC chemokine

nomeclature CXCL8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

C chemokines aka

A

Gamma Chemokine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Gamma Chemokine

A

aka C chemokine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Describe the cystein residues of Gamma Chemokines

A

C chemokine or gama chemokine LACK the FIRST and THIRD cysteines.

CHEMOATTRACTANT for SPECIFIC LYMPHOCYTES subsets

NOMENCLATURE XCL1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

CXXXC Chemokines only member is

A

CX3CL1 and cleaved FROM THE CELL SURFACE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

A chemokine that is attracted to specific LYMPHOCYTE subsets.

A

Gamma Chemokine, C chemokine, XCL1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What type of chemokine is CXCL10

A

Alpha Chemokine, CXC chemokine, has an a,a b/w FIRST and THIRD CYSTEINE Residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What type of chemokine: EOTAXIN specifically recruits EOSINOPHILS

A

Beta Chemokine, CC chemokine

has adjacent first and 2nd cystein residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What type of chemokine is cleaved from the cell surface

A

CXXC chemokine, CX3CL1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What type of chemokine is not a chemoattractant for NEUTROPHILS?

A

Beta chemokine or CC chemokine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What type of chemokine is XCL1?

A

Gamma or C chemokine that lacks the first and 3rd cystein residue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What type of chemokine is CCL5?

A

Beta chemokine, CC chemokine with adjacent first and second cysteine residue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

PAMPS and DAMPS induce the expression of specific WHAT that in turn recruit specific immune cells to injury/infection site and also RECRUITS CYTOKINES?

A

CHEMOKINE

CHEMOKINES RECRUIT SPECIFIC IMMUNE CELLS & CYTOKINES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

T/F can chemokines RECRUIT CYTOKINES?

A

Yes

Chemokines in response to PAMP/DAMP recruit specific immune cells and cytokines to site of infection/injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

CCL2 is expressed to the site of WHAT and presented on WHAT recruits what CELL that has CCLR2?

A

CCL2 is tethered to the surface of DAMAGED ENDOTHELIA and presented on ECM

monocyte with the CCL2R is recruited there

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

The (monocyte/ECM) has the CCR2 receptor and the (monocyte/ECM) has the CCL2?

A

The MONOCYTE has the CCR2 RECEPTOR and the ECM has CCL2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

macrophage full of phagocytosed debri

A

FOAM CELL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

ADAPTIVE immune response is coordinated by regulating both the WHAT and the WHAT?

A

Regulating both THE EXPRESSION of the CHEMOKINE and the EXPRESSION of the CHEMOKINE RECEPTOR

ADAPTIVE IMMUNITy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What chemokine is expressed at high levels at the Lymph Node

A

CCL21

51
Q

Which Cells are home to and are localized w/in the LYMPH NODE?

A

Naive T cells with their corresponding CCR7 Receptors

52
Q

After encountering PAMPs and DAMPS, WHAT CELLS leave the tissues, carrying antigen and expressing CCR7 to the LN?

A

DENDRITIC CELLS

53
Q

Foam Cells

A

MACROPHAGE full of phagocytosed debri

54
Q

Dendritic Cells carrying antigen and expressing CCR7 are drawn to the LN because?

A

The high amounts of CCL21 expressed at LYMPH Nodes

55
Q

What cells present antigen to what cells their antigen?

A

DENDRITIC CELLS (ACTIVATED/MATURE) present their antigen to NAIVE T CELL AT LYMPH NODE

56
Q

without CCR7 receptor; they can no longer see CCL21.

A

Activated Effector T cells

57
Q

These cells down-regulate their CCR7 and leave LN because they aren’t retained in LN by CCL21 anymore

A

Activated Effector T cells

58
Q

Why is there NOT a break out chemokine based therapies?

A

Chemokines participate in a WIDE VARIETY of FUNCTIONs from development, normal function, to tissue defense/reapir. It’s hard to target disease specific processes

59
Q

Chemokine Antagonist are studied as potential therapies for WHAT, WHAT, and WHAT?

A

Chemokine Antagonist for:

1) chronic inflammatory disease
2) autoimmune disorders
3) LYMPHOMAS

60
Q

Activated Effector T cells down regulated WHAT and leave WHERE because they are no longer retained by WHAT?

A

Activated effector T Cells DOWN REGULATE CCR7 and LEAVE LN bc they aren’t retained by CCL21 anymore

61
Q

CT tissues of any organ

A

Stromal Cells

62
Q

cells that perform the biological function of their organ

A

Parenchymal Cells

63
Q

Cells that wrap around endothelial cells

A

Pericytes

64
Q

Stuff that are relased by activated immune cells and STRESSED stromal cells.

A

Cytokines are SOLUBLE and small 25kD

65
Q

Cytokine has both what and what actions?

A

Cytokines has both AUTOCRINE and PARACRINE action

66
Q

Regulating adjacent cells

A

Paracrine

67
Q

regulating self behavior

A

Autocrine

68
Q

these stuff can even act SYSTEMICALLY

A

Cytokines
examples

TNF
IL-6
IL-1

on LIVER’s production of chemical mediators of inflammation

  • fibrinogen
  • crp protein
  • sap protein
  • SP-A/SP-D
  • MBL
69
Q

Exists as a monomer

A

IL-4 a cytokine

70
Q

Exists as a trimer

A

TNF a cytokine

71
Q

Stuff that primary acts as chemoattractants for specific leukocyte subsets

A

Chemokines

72
Q

this stuff during early innate immune response to damage attracts monocytes and macrophages to sites of injury and infection

A

CCL2

73
Q

this recruits APC cells to LN to present antigen to naive T cells

A

CCL21

74
Q

TNF, IL-6, IL-1

A

Examples of systemic cytokines

75
Q

Cytokine are NOT GPCRs T/F

A

True

76
Q

These receptors are activated by DIMERIZATION.

A

Cytokine Receptors

77
Q

IL-4

A

exist as a monomer

78
Q

TNF

A

exist as a trimer

79
Q

How are cytokine action mediated?

A

JAK/STAT linked receptors

80
Q

Cytokine receptor’s cytoplasmic domain bind WHAT

A

Janus Kinases (JAKs)

81
Q

After cytokine binds what happens to the receptor

A

the receptor dimierizes

82
Q

When cytoplasmic JAKs are brought together they

A

1) phosphrylate each other

2) phophrylate the cytoplasmic part of the receptor

83
Q

WHAT transcriptional factors bind to which part of the receptors and what happens to them?

A

STATs bind to the PHOSPHRYLATED RECEPTORS and are PHOSPHRYLATED by JAKs

84
Q

Phosphrylated Stats form what and translocate where to initiate what?

A

Phosphrlylated stats dimerize and translocate to the nucleus to initiate new gene transcription

85
Q

…phsophrylate themselves and cytoplasmic protion of the cytokine receptor

A

JAKs

86
Q

….bind to phosphrylated regions of cytoplasmic protion of the cytokine receptor

A

STATs

87
Q

….dimerizes the WHAT bringing together the JAKS

A

CYTOKINE binding dimerizes the CYTOKINE RECEPTOR and brings JAKS together to phosphrylate one another and also the cytoplasmic portion of the receptors

88
Q

What must occur before STATs can translocate to nucleus and initiate gene transcription

A

STATs have to bind to the cytoplasmic phsophrylated part of the cytokine receptor to by phosphrylated by the JAKs and dimierize before translocating

89
Q

What must occur before STATs are able to bind to the cytoplasmic portion of the cytokine receptor?

A

JAKs have to posphrylate themselves and the cytopalsmic protions of the cytokine receptor

90
Q

Activates NK cells, which induces the differentiation of CD4 T cells into Th1 cells

A

IL-12 cytokine

91
Q

….lymphocyte activation, increased Ab production

A

IL-6 cytokine

92
Q

….activates vascular endothelium, lymphocytes, local tissue destruction, increasses access of effector cells

A

IL-1Beta

93
Q

….activates vascular endothelium, increases vascular permeability, leads to increased entry of IgG and compelment, and cells to tissues and increased fluid drainage to lymph nodes

A

TNF-alpha

94
Q

….cause FEVER and induces ACUTE PHASE PROTEIN PRODUCTION

A

IL-6

95
Q

…..causes FEVER and MOBILIZES METABOLITES, SHOCK!!!!!

A

TNF-alpha

96
Q

….causes FEVER and PRODUCTION of IL-6

A

IL-1beta

97
Q

IL-12

A

Activates NK cells, which induces the differentiation of CD4 T cells into Th1 cells

98
Q

TNF-alpha

A

….activates vascular endothelium, increases vascular permeability, leads to increased entry of IgG and compelment, and cells to tissues and increased fluid drainage to lymph nodes

…..causes FEVER and MOBILIZES METABOLITES, SHOCK!!!!!

99
Q

IL-1Beta

A

….activates vascular endothelium, lymphocytes, local tissue destruction, increasses access of effector cells
….causes FEVER and PRODUCTION of IL-6

100
Q

IL-6 cytokine

A

….lymphocyte activation, increased Ab production

….cause FEVER and induces ACUTE PHASE PROTEIN PRODUCTION

101
Q

Actions of cytokines, list global, local, and final net effects.

A

Global

behavioral responses like anorexia, lethargy, slow-wave sleep, decreased social/exploratory behaviro
&
Systemic immune respones

Local
Regulating different lymphocytes, APC, and innate

Final Net effects
- based on RATIO and CONCENTRATIONS of specific cytokines present

102
Q

Systemic effects of cytokines

A

Fever,

production of IL-6 which leads to lymphocyte activation, increased ab production

Mobilization of metabolites

Shock

103
Q

Sickness behavior is associated with

A
Cytokines
IL-1beta
IL-6 
TNF alpha 
secreted by MACROPHAGES act on BRAIN to induce sickness behavior
104
Q

What produces IL-1beta, IL-6, TNF-alpha

A

Macrophage

105
Q

Which anatomy does IL-1Beta, IL-6, and TNF alpha act on to produce sickness behavior

A

Brain

106
Q

Which MHC class is presented on all cells and with the exception also platelets

A

MHC I

107
Q

Which MHC class is presented only on APC cells

A

MHC II

108
Q

What are APC cells?

A

dendritic cells, macrophages, and B cells

109
Q

Cytokines produced by APC cells determine the final effector function of

A

Antigen-activated T cell

110
Q

Different cytokines are produced by stage and type of infection/tissue damage thus you can use cytokine type to find out

A

the STAGE of the disease and the PATHOGEN SPECIFIC IMMUNE RESPONSES

111
Q

can amplify innate immune responses

A

cytokines

112
Q

The effector function of Antigen-activated T cells is determined by

A

Cytokines PRODUCED BY APC cells

113
Q

Biologics like MAB can block cytokine actions

A

Anti-TNF therapies

114
Q

Anti-TNF therapies have been life-changing for

A

Rheumatoid Arthritis and Psoriasis

115
Q

Side effects on Anti-TNF therapies

A

TNF is required for NORMAL pathogen defense

  • immunoDEFICIENT
  • TNF required to promote proliferation of myeliating cells and remyelination in disease like ms and guillian-barre syndrome
  • INCREASE demyelination and NERVE DAMAGE in pt with CNS disease
116
Q

…helps determine stage and pathogen specific immune responses

A

cytokine

117
Q

What determines the final effector function of antigen-activated T cell?

A

Cytokines produced by APCs

118
Q

Sickness behavior promotes a conservation of resources with generation of toxic environment for invading pathogen T/F

A

True

119
Q

….required for normal pathogen defense and required in brain to promote proliferation of myelinating cells and remyelination

A

TNF

120
Q

Why aren’t anti-TNF used as first line therapy

A
  • demyelination and nerve damage in pt with CNS disease

- immuno deficient since need TNF normally to fight off pathogens

121
Q

Pericytes

A

cells that wrap around endothelial cells

122
Q

Parachyemal Cells

A

cells that perform the organ’s function

123
Q

Stromal Cell

A

CT of any organ