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

Lecture 9 (4b) - Cytokines Flashcards

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
21
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

A

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

22
Q

IL-10

A
  • B cell growth factor

* immunosuppressive cytokine

23
Q

IFN- γ

A
  • anti-viral

* activates macrophages

24
Q

IL-2 secretion

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
Q

IFN-γ

A

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
Q

Toll-like receptors

innate immunity

A

molecules on the surface of mammalian cells which recognize components of bacteria and viruses to alert the immune system

27
Q

TLR2
+
TLR6 (/ TLRX)

A
  • lipoproteins
  • lipopolysaccharides
  • PGN (gram-positive)
  • zygomosan (yeast)
  • GPI anchor (T. cruzi)
28
Q

TLR4
+
MD-2

A
  • LPS (Gram-negative)
  • Taxol (plant)
  • F protein (RS virus)
  • hsp60 (host)
  • fibronectin (host)
29
Q

TLR5

A

flagellin

30
Q

TLR9

A

CpG DNA

31
Q

When bacteria interact with macrophages through TLRs, macrophages release large amounts of cytokines

A 
IL-1
TNFα
IL-6
IL-8
nitric oxide
IL-12*******
MMPS
32
Q

Actions of IL-12

NK cells

A

increased cytosolic activity

and

stimulate IFN-γ

  • -> IFN-γ
  • -> macrophage activation, killing of phagocytosed microbes
33
Q

Action of IL-12

CD8+ T cell

A

stimulation of IFN-γ secretion

  • -> IFN-γ
  • -> macrophage activation, killing of phagocytosed microbes
34
Q

Action of IL-12

Naive CD4+ T cell

A

Th1 cell

  • -> stimulate IFN-γ secretion
  • -> macrophage activation, killing of phagocytosed microbes
35
Q

Bacteria in skin, Lagerhans recognize via TLR

A

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
Q

Cytokines are important in mobilizing inflammatory cells into tissues

A

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
Q

Septic shock

A
  • 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
Q

How - septic shock

A

Cell envelope of gram-negative bacteria

  • -> endotoxin (CLPs)
  • -> TLR4
  • -> macrophage releases cytokines
  • -> local inflamation
  • -> septic shock
39
Q

Disseminated intravascular coagulation in small vessels

A

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
Q

Chemokine

A

• 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
Q

Neutrophils move by

A

chemotaxis

• move up chemokine concentration gradient

42
Q

There are lots of chemokines, often

A

binding to the same receptor
• redundancy
• knock out 1 chemokine and another does its function

43
Q

IL-8

CXCL8

A

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
Q

Chemokines in extravasation

A
  1. capture
  2. activation
  3. adhesion
  4. transmigration
    • ICAM-LFA1
    • ICAM2 brings cells through
45
Q

Anti-inflammatory cytokines

A
  • 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
Q

Damaging cytokines vs inhibitor cytokines

A

damaging - TNF, IL-1, IL-6

inhibitory - IL-10, TGFβ

• balance is anti-inflammatory usually

47
Q

Cytokine storm

A

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
Q

Anti-TNFα antibodies

A
  • rheumatoid
  • IBD
  • asthma
  • psoriasis
49
Q

Anti IL-15 antibodies

A

rheumatoid

50
Q

Soluble IL-1R

A
  • rheumatoid

* psoriasis

51
Q

Summary

A
  • cytokines are critical for immunity
  • complex, redundant, wide-ranging
  • can kill you in excess

Basic Immunology (15 decks)

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