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PDAT4 > 12 - Cytokines > Flashcards

12 - Cytokines Flashcards

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1
Q

General CYTOKINE Traits

A

Are NOT stored
are rapidly synthesized & secreted after stimulation

Cellular Responses consist of:
Changes in GENE EXPRESSION
VVV
New Functions / PROLIFERATION of target cell

  • EXCEPTIONS:*
  • *Chemokines / TNF**
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2
Q

Which CYTOKINES do NOT result in
New Functions or Proliferation
after gene expression?

A

CHEMOKINES
induce motility

TNF
induce apoptosis

do NOT need activation of NEW PROTEINS
SUFFICICIENT ON THEIR OWN

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3
Q

Regulation of Cytokines

A

QUANITITY of cytokine Produced

EXPRESSION** or **DOWN-REGULATION
of Cytokine Receptors

Low Affinity Receptors
are found on MOST CELLS, in LOW QUANTITY

High Affinity Receptors
are expressed on ANTIGEN ACTIVATED cells

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4
Q

3 Types of CYTOKINE action

A

Autocrine
Act on SELF

Paracrine
Acts on NEARBY cell

Endocrine
Passes through CIRCULATION –> DISTANT CELL

IL-2 DOES ALL 3

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5
Q

What is PLEIOTROPY?

A

Pleiotropy

ONE CYTOKINE can act on MULTIPLE CELL TYPES

DIFFERENTLY

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6
Q

What is REDUNDANCY?

A

Redundency

MULTIPLE CYTOKINES
have the
SAME EFFECT** & use the **SAME SIGNALING SUBUNITS

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7
Q

Synergy / Antagonism
properties of Cytokines

A

Synergy
cytokines act together –> induce something

  • *Antagonism**
  • another cytokine** –> *_antagonizes action of another_
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8
Q

How do we CLASSIFY CYTOKINES?

A

BY THEIR ACTION

Functional Classification of Cytokines

Mediators & Regulators of INNATE & ADAPTIVE IMMUNITY

Stimulators of Hematopoeiesis

Chemokines

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9
Q

What are the PRIMARY PRODUCERS of
Cytokines of the INNATE IMMUNE SYSTEM?

A

MONONUCLEAR PHAGOCYTES
Dendritic Cells + Macrophages

Also by,
Endothelial + Epithelial Cells

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10
Q

What do these cytokines MEDIATE & REGULATE?

TNF-A

IL-1 // IL-10 // IL-12

INF-A + INF-B

Chemokines

A

INNATE IMMUNE SYSTEM

Produced primarily by:
Mononuclear Phagocytes = Dendritic cells + Macrophages

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11
Q

Which Cytokine?

Mediator of ACUTE INFLAMMATORY RESPONSE
to GRAM (-) Bacteria & other microbes

Induces INFLAMMATION
in an effor to limit spread of infection

Responsible for many
systemic complications of severe INFECTION

A

TNF-A

Mediator & Regulator of INNATE IMMUNITY

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12
Q

Low Quantities of TNF-A cause what?

TNF-A Biologic Actions

A

LOCAL INFLAMMATION

Neutrophil Activation –> Chemokine Production

Endothelial cells activated to
secrete chemokines + adhesion molecules

some Apoptosis

Increased Vascular permeability / Redness / Swellin
Inflammation

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13
Q

MODERATE Quantities of TNF-A cause what?

TNF-A Biologic Actions

A

SYSTEMIC EFFECTS

Brain –> produces FEVER

Hepatocytes produce Acute Phase Proteins

Bone marrow leukocyte production is increased

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14
Q

HIGH QUANTITIES of TNF-A cause what?

TNF-A Biologic Actions

A

SEPTIC SHOCK

Heart -> low output due to inhibition of myocardial contractility

Vascular endothelium

HypoGlycemia

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15
Q

Which Cytokine?

Pro-Inflammatory with TNF-Alpha

@Low Concentrations
local inflammation

@HIGH concentrations
Pyrogen / Cachexia / Acute Phase Proteins Secreted

A

IL-1

Secreted by Activated Macrophages

Mediator & Regulator of INNATE IMMUNITY

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16
Q
  • *IL-1 + TNF-A**
  • *Functions Together**

Mediator & Regulator of INNATE IMMUNITY

A

they make ENDOTHELIAL CELLS:

  • *LEAKY to fluids**
  • -> influx of plasma w/ AB’s
  • *STICKY for leukocytes**
  • -> influx of neutrophils –> monoctes/lymphocytes
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17
Q

DIFFERENCES between IL-1 and TNF-A

Mediator & Regulator of INNATE IMMUNITY

A

IL-1

cannot cause cell APOPTOSIS

cannot cause SHOCK by itself

binds DIFFERENT RECEPTOR, but produces a similar effect

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18
Q

What Cytokine?

INDUCER of ADAPTIVE Immune response
VVV
Stimulates DIFFERENTIATION of
Th -> Th1 (produce INF-y) –> macrophage activation
&
Enhances Cytolytic fxn of Activated CD8+ T-cells
–> LYSIS of infected cell

Principle mediator of:
EARLY INNATE IMMUNE RESPONSE

A

IL-12
Th –> Th1 producing TNF-y
macrophage activation -> kill phagocytosed microes
Enhance CD8+ Tc
lysis of infected cell

from activated macrophages + dendritic cells

Mediator & Regulator of INNATE IMMUNITY

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19
Q

What Cytokine?

INHIBITOR of host immune responsed involving macrophages
INHIBITS Cellular Immunity
in favor of HUMORAL RESPONSE

INHIBITS production of IL-2** & **TNF-a
by activated macrophages

INHIBITS expression of Costimulators** & **MHC
by macrophages

A

IL-10

From
Th2 cells + late stage macrophages

Mediator & Regulator of INNATE IMMUNITY

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20
Q

What Cytokine?

Interfere with VIRAL REPLICATION
response to dsRNA

LEUKOCYTE INTERFERON

Major source is
Mononuclear Phagocytes & Viral-Infected Cells

A

INF-a

Mediator & Regulator of INNATE IMMUNITY

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21
Q

What Cytokine?

Interfere with Viral Replication
response to dsRNA

FIBROBLAST INTERFERON

Major source:
Fibroblast + Virally Infected Cells

Study These Flashcards
A

INF-B

fibroBlast interferon

Mediator & Regulator of INNATE IMMUNITY

22
Q

4 Main Functions of

INF-A + INF-B

Study These Flashcards
A

Both Bind SAME RECEPTOR & Ilicit SIMILAR BIOLOGIC RESPONSE

Induce Resistance
to viral replication in all cells

Increase MHC1** + **Antigen presentation

Activate Dendritic Cells + Macrophages

Activate NK Cells
to kill virus-infected cells

23
Q

Which Cytokine

Enlist ASSISTANCE from ADAPTIVE IMMUNE SYSTEM?

Study These Flashcards
A

IL-12

Th0 -> Th1 differentiation
Th1 –> INFy produciton

Enhance CytoLYTIC Fxn of CD8+ Tcytotxic cells

24
Q

What Cytokine

INHIBITS / STOPS the INNATE/CELLULAR RESPONSE

Study These Flashcards
A

IL-10

Inhibits production of
IL-12 & TNF-A
by activated macrophages

Inhibits expression of
Costimulators + MHC
by macrophages

25
**What Type of Cytokines?** **IL-2** // **IL-4** // **IL-5** **INF-y** **TGF-B**
Mediators & Regulators of **_ADAPTIVE IMMUNITY_**
26
**What Cytokine?** **_Growth Factor_** for **Ag-stimulate T-cells** responsible for **T-Cell Clonal EXPANSION** after AG recognition * *_Autocrine/Paracrine Effect_** on: * *T-Cell proliferation / NK activation / B-Cell Proliferation** **_Promotes Cell-Cycle Progression_** **High Concentration --\> APOPTOTIC DEATH** of AG-Activated T-cells
**_IL-2_** ## Footnote from **Th0** & **Th1** **Naive T-cell + IL-2 = Th0** Mediators & Regulators of ADAPTIVE IMMUNITY
27
**What Cytokine?** ``` Major Stimulus for **_IgE AB class switching_** ``` _***Antagonizes*** the **Macrophage-Activating Effects of INF-y**_ --\> *inhibits cell mediated immunity* Major stimulus for **differentiation** of * *Th0 --\> Th2** - -\> **Activation of B-cells**
**_IL-4_** ## Footnote From Th2 Cells Mediators & Regulators of ADAPTIVE IMMUNITY
28
**What Cytokine?** Major Stimulus for: **_B-Cell Differentiation_** & **_Class Switching_** **_Activates EOSINOPHILS_** to destroy Parasite **IL-4 stimulates IgE** --\> **opsonize parasites & binds eosinophils**
**_IL-5_** ## Footnote From Th2 Cells Mediators & Regulators of ADAPTIVE IMMUNITY
29
**What Cytokine?** PRINCIPAL: **_MACROPHAGE ACTIVATING CYTOKINE_** stimulates production of **cytotoxic molecules** by macrophages ***_INHIBITS PROLIFERATION of TH2 CELLS_*** **Th0 -\> Th1** Cell differentation Stimulates **Expression of MHC** & **Costimulatory Molecules** on APC **Isotype Switching** to **opsonizing ABs in B-cells**
**_INF-y_** ## Footnote From **CD8+ Tcells** & **Th1 cells** Mediators & Regulators of ADAPTIVE IMMUNITY
30
**Which cytokine** is the ## Footnote **MACROPHAGE ACTIVATING CYTOKINE?**
**_INF-y_** ## Footnote Also ***_Inhibits proliferation of Th2 Cells_***
31
**INF-y** **Main Functions & Image**
**Macrophage Activation** **Isotype Switching -\> Opsonizing AB's** **Th0 -\> Th1** ***Inhbits Th2 Production*** **Increased MHC expression + Costimulatory Molecules on APC**
32
**What Cytokine?** **_INHIBITORY CYTOKINE of ADAPTIVE IMMUNITY_** *_Inhibits:_* **T-Cell Proliferation & effctor Fxn B-Cell Proliferation Macrophages** Promotes **IgA Isotype Switching** in **B-cells**
**_TGF-B_** ## Footnote **Th0 -\> _TREG_** From **Lymphocytes / macrophages / Platelets** Mediators & Regulators of ADAPTIVE IMMUNITY
33
**What CYTOKINE?** **Induces proliferation of T-REGULATORY CELLS Tregs?**
**_TGF-B_** **TREGS** --\> **TGF-B & IL-10** **_Inhibitory Cytokine of Adaptive Immunty_**
34
**Key Differences Between ADAPTIVE & INNATE Immunity Cytokines** **chart**
35
**Cytokines that are Stimulators of HEMATOPOIESIS**
Produced by: **Bone Marrow / Leukocytes** Promote: **Differentiation & Expansion of Bone Marrow Progenitor Cells** Drug Examples / Therapeutics: **Stem Cell Factor M/G - CSF = Colony-Stimulating Factors IL-3**// I**L-7**//**IL-5**//**IL-11**
36
**What Cytokine/Drug is used to: Stimulate RBC proliferation?**
**_Erythropoietin_** **Epogen - Epoetin Alpha Procrit**
37
**What Cytokine/Drug is used to INDUCE NEUTROPHIL PRODUCTION**
**_G-CSF_** G- Colony Stimulating Factors ## Footnote **Filgrastin = Neupogen**
38
**What Cytokine/Drug is used to INDUCE PLATELET PRODUCTION?**
**_Thrombopoeietin_** **_IL-11_**
39
**What is the MOST COMMON cytokine Receptor?**
**_CLASS 1_** ## Footnote **_Cytokine Receptor Hematopoietin_**
40
**Cytokine Receptors**
Grouped Based on their: * *_EXTERNAL DOMAINS_** * signaling domains are often SHARED* **_5 Major Families_** **Class 1 Cytokine Receptor hematopoietin** TNF Receptor Class 2 Cytokine Receptor Interferon IG Superfamily Receptor Chemokine Receptor
41
**What type of PROPERTY of CYTOKINE RECEPTORS?** Association with the **SAME BETA SUBUNIT** required for **Signal Transduction**
**_REDUNDANCY_**
42
**What type of PROPERTY of CYTOKINE RECEPTORS?** **Competition of Ligand**-**binding chains** of **_Different Receptors_** for a **COMMON SUBUNIT**
**_ANTAGONISM_**
43
**How is Cytokine Receptor Expression HIGHLY REGULATED?**
***_Inactive Cells_*** Express **Low Affinity Receptors** **_Activated Cells_** express **HIGH affinity receptors**
44
**_IL-2 RECEPTOR_**
_**A-Chain = Cytokine** **Binding Component**_ ***Low Affinity, just binding*** _**B + Y -Chain =** **Signal Transduction**_ **Medium Affinity**, beta + gamma * *_All 3 = A+B+Y_** * *complete signal transduction**, * *_ONLY IN ACTIVATED T-CELLS_**
45
**_Cytokine Signal Transduction_** **IL-2**
* *IL-2 Receptor subunit** **Gamma + Beta** is associated with * *_JAK_** **Cytokine Binding -**-\> **JAK activation** VVV docking sites for **STATs** signal transduction to: **Growth + Proliferation + Survival Transcription Regulation + Effector Differentiation** *hard to regulate due to UBIQUITOUS = found everywhere*
46
What does a **_Mutation in Class 1 Cytokine Receptor_** **_GAMMA SUBUNIT_** cause?
Class 1 is the MOST COMMON RECEPTOR **Gamma Subunit** is necessary for **Signal Transduction** VVV ***Unable to TRANSMIT the CYTOKINE SIGNAL*** VV **_Increases SUSCEPTABILITY to INFECTIONS_**
47
**What Disease is caused by a** **Enterotoxin** derived from **Gram Positive Bacteria** **= SUPERANTIGEN**
**_TOXIC SHOCK SYNDROME_**
48
**_Toxic Shock Syndrome_**
**Enterotoxin** from **Gram + bacteria = _SUPERANTIGEN_** **Crosslinks TCR + MHC2** on **APC** resulting in **over stimulation cytokine production by T-cells** Extremely high lvels of cytokines; **_TNF-A**_ & _**IL-1_** Fever / Diarrhea / Clotting / HypoTension / shock ***_RARELY FATAL_***
49
**_Bacterial Septic Shock_**
**ENDOtoxin** derived from **Gram Negative bacteria** Bacterial LPS **Over-Stimulates Cytokine production by Macrophages** Extremely high levels of inflammator cytokines: **_IL-1 & TNFa_** (like Toxic Shock Syndrome) Fever / blood clotting / rash / diarrhea / hypotension / shock **_OFTEN FATAL_**
50
**Two Mechanisms of** **Cytokine ANTGONISM / INHIBITION**
**PROTEINS produced** by cells to **l_ocally regulate cytokine activity_** Ex. **IL-1 Receptor Agonist** **_Cytokine binding domain RELEASED_** from cell surface as a result of **Enzymatic Cleavage** Ex- **IL 2/4/6/7 + INFy + TNFb**
51
**Cytokine Map**
52

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