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Basic Immunology > Lecture 9 (4b) - Cytokines > Flashcards

Lecture 9 (4b) - Cytokines Flashcards

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1
Q

Receptors transmit signals

A

from the cell surface to the nucleus to change gene expression and function
• can work locally, at a distance, at low levels
• signals from - CYTOKINES, chemical messengeres, hormones

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2
Q

IL =

A

interleukin
• called lymphokines
• can sometimes be non-immune cells and target non-immune cells

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3
Q

Cytokines in antigen presentation

A 
IL-
1
16
12
18
23
27
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4
Q

Cytokines from the gut epithelium to the T cell

A

IL
7
15

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5
Q

Cytokines in costimulation

A

APC : Tcell
CD40 : CD40L
CX40L : CX40
CD80/86 : CD28

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6
Q

Cytokines in inflammation

A 
from T cell
IL
5
13
17
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22

TNFα IFNγ

  • -> macrophage
  • -> TNFα IL-6 IL-1
  • -> inflammation

(–> Crohn’s disease)

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7
Q

Cytokines for T cell proliferation

A

IL
2
21

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8
Q

Cytokines are

A

small proteins secreted by the cells of the innate and adaptive immune systems

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9
Q

Cytokine secretion is

A

brief, self-limited

transient synthesis

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10
Q

Cytokine are usually not

A

stored in the cells (except mast cells store it in cells)

• they are synthesized by new gene transcription

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11
Q

Transcription of cytokine genes is

A

a transient process

• cytokine mRNAs are unstable

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12
Q

Cytokines, like other polypeptide hormones, mediate their effects by

A

binding to specific receptors on the surface of target cells
• these receptors are often on many cell types
• immunology is context-specific

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13
Q

Cytokines are pleiotrophic

A 
they have many functions
• made by many cell types
• same cytokine made by different cells
• cytokine receptors on many cell types
• have many different effects on different cell types

• many cells make them, many cells respond to them, response depends on what it binds

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14
Q

Cytokines produced as a result of activation of the

INNATE IMMUNE SYSTEM

A 
• type 1 interferon
• interleukins
- IL-1
- IL-6
- IL-12
• TNF
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15
Q

Cytokines produced as a result of activation of the

ADAPTIVE IMMUNE SYSTEM

A 
• IFNγ
• interleukins
- IL-2
- IL-4
- IL-5
 (IL-4 and IL-5 for Th2)
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16
Q

Cytokines that stimulate immature leukocyte growth and differentiation

A
  • IL-3

* colony stimulating factors

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17
Q

Interleukins vs cytokines

A
  • all interleukins are cytokines

* not all cytokines are interleukins

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18
Q

T cells make lots of cytokines when activated

A

switch on T cell by binding TCR
make nothing –>
activated = lots of transcriptional activation
= mediated by cytokines, lots of different targets

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19
Q

IL-2

A

T cell growth factor

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20
Q

IL-3

A

mast cell growth factor

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21
Q

IL-4 and IL-5

Study These Flashcards
A

B cell growth factor
• made by Th2
• IL-5 = eosinophil growth factor

22
Q

IL-10

Study These Flashcards
A
  • B cell growth factor

* immunosuppressive cytokine

23
Q

IFN- γ

Study These Flashcards
A
  • anti-viral

* activates macrophages

24
Q

IL-2 secretion

Study These Flashcards
A

cloned as T cell growth factor, does other things:
• induces Th cell, induced by Th cell
• B cell - stimulation of division
• T cell - stimulation of division, IFNγ release (and other mediators)
• NK cell - increase NK cell activity (lymphokine activated killer)
• monocyte activation

25
IFN-γ
made by T cells, important in cell-mediated immunity • induced by: NK cells, T cells • endothelial cells - activation • NK cells - increase in NK cell activity • many cell types - induction of Class I or Class II MHC • B cell - differentiation, stops cell division • T cell - activation • many cell types - weak anti-viral activity, stops cell division, hematopoiesis stops • macrophage - activation • granulocyte - activation
26
Toll-like receptors | innate immunity
molecules on the surface of mammalian cells which recognize components of bacteria and viruses to alert the immune system
27
TLR2 + TLR6 (/ TLRX)
* lipoproteins * lipopolysaccharides * PGN (gram-positive) * zygomosan (yeast) * GPI anchor (T. cruzi)
28
TLR4 + MD-2
* LPS (Gram-negative) * Taxol (plant) * F protein (RS virus) * hsp60 (host) * fibronectin (host)
29
TLR5
flagellin
30
TLR9
CpG DNA
31
When bacteria interact with macrophages through TLRs, macrophages release large amounts of cytokines
``` IL-1 TNFα IL-6 IL-8 nitric oxide IL-12******* MMPS ```
32
Actions of IL-12 | NK cells
increased cytosolic activity and stimulate IFN-γ - -> IFN-γ - -> macrophage activation, killing of phagocytosed microbes
33
Action of IL-12 | CD8+ T cell
stimulation of IFN-γ secretion - -> IFN-γ - -> macrophage activation, killing of phagocytosed microbes
34
Action of IL-12 | Naive CD4+ T cell
Th1 cell - -> stimulate IFN-γ secretion - -> macrophage activation, killing of phagocytosed microbes
35
Bacteria in skin, Lagerhans recognize via TLR
macrophage makes TNFα and IL-1 --> endothelial cells, makes them sticky --> neutrophils (in blood) stick to surface and go through • localize phagocytes where bugs are
36
Cytokines are important in mobilizing inflammatory cells into tissues
inflammation --> cytokines increased on endothelial cells (eg ICAM and selectin) --> neutrophil finds these because it has receptors (LFA1) --> neutrophil rolls, slows down and anchored by LFA1-ICAM --> stops ==> through endothelial into tissue
37
Septic shock
* most common cause of death in ICUs in the US * dissemination of infections into the vasculature * caused by systemic microbial infection, most often by gram-negative infection (endotoxic shock) but can also occur with gram-positive and fungal infections * infection from site into blood
38
How - septic shock
Cell envelope of gram-negative bacteria - -> endotoxin (CLPs) - -> TLR4 - -> macrophage releases cytokines - -> local inflamation - -> septic shock
39
Disseminated intravascular coagulation in small vessels
little clots in small vessels --> punch holes in sides --> vessels so sticky can't get through (disseminated intravascular coagulation in small vessels) • lack of oxygen to the extremities because blood vessels are blocked --> tissue dies • • cytokines here are bad
40
Chemokine
• a small subgroup or superfamily of cytokines that are released during the initial phase of cell response to injury, antigens, and invading microorganisms • selectively attract leukocytes to inflammatory foci during both cell migration and activation (hemotatic - draw cells into body)
41
Neutrophils move by
chemotaxis | • move up chemokine concentration gradient
42
There are lots of chemokines, often
binding to the same receptor • redundancy • knock out 1 chemokine and another does its function
43
IL-8 | CXCL8
a chemokine that attracts neutrophils into tissues • macrophage in lung making IL-8, binds CXCR1/2, chemotaxes it through into tissue and causes damage (CXCR1/2 causes damage)
44
Chemokines in extravasation
1. capture 2. activation 3. adhesion 4. transmigration • ICAM-LFA1 • ICAM2 brings cells through
45
Anti-inflammatory cytokines
* IL-10 made by T cells, B cells, macrophages * TNF, IL-1, IL-6 - pro-inflammatory • transforming growth factor TGFβ (--> Treg) - inhibits T cell activation - inhibits antigen presentation
46
Damaging cytokines vs inhibitor cytokines
damaging - TNF, IL-1, IL-6 inhibitory - IL-10, TGFβ • balance is anti-inflammatory usually
47
Cytokine storm
positive feedback loop between cytokines and immune cells --> elevated levels of cytokines • TGN1412 (anti-CD28) activated all T cells --> cytokine storm • antibodies to Cd28 usually activating for T cells • TGN1412 (anti-CD28) meant to induce unresponsiveness in T cells • given to patient with T cell disease, would switch T cells off • cytokine storm same as septic shock
48
Anti-TNFα antibodies
* rheumatoid * IBD * asthma * psoriasis
49
Anti IL-15 antibodies
rheumatoid
50
Soluble IL-1R
* rheumatoid | * psoriasis
51
Summary
* cytokines are critical for immunity * complex, redundant, wide-ranging * can kill you in excess

Basic Immunology (15 decks)

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