8. cytokines and chemokines

Question 1

what is a cytokine?

Answer 1

soluble mediator
ligate receptor and trigger a signalling cascade
leads to activated transcription of specific genes

Question 2

cytokines in haematopoiesis

Answer 2

GM-CSF
G-CSF
SCF
IL-6
IL-5
IL-2
IL-11
EPO
TPO
\+ others (eg. il-3)

Question 3

GM-CSF in haematopoiesis

Answer 3

differentiation to :
- common myeloid progenitor 
- mast cell
- myeloblast 
\+ myeloblast offspring: basophil, neutrophil, eosinophil, monocyte

Question 4

G-CSF in haematopoiesis

Answer 4

differentiation to:

• mast cell
• basophil
• neutrophil

Question 5

SCF in haematopoiesis

Answer 5

mast cell

Question 6

IL-6 in haematopoiesis

Answer 6

mast cell

Question 7

IL-5 in haematopoiesis

Answer 7

eosinophil

Question 8

IL-2 in haematopoiesis

Answer 8

T lymphocyte

Question 9

IL-11 in haematopoiesis

Answer 9

megakaryocyte

Question 10

EPO in haematopoiesis

Answer 10

erythrocyte

Question 11

TPOin haematopoiesis

Answer 11

megakaryocyte

Question 12

mediators of host defence

Answer 12

antiviral mediatros (interferons)
immune activators
cytotoxins

Question 13

interferons

Answer 13

antiviral mediators
products of virus-infected cells
interfere with viral replication

Question 14

interferon examples

Answer 14

IFN-alpha - made by lymphocytes
IFN-beta - made by fibroblasts
IFN-alpha - made by lymphocytes and NK cells

Question 15

immune activators

Answer 15

lymphocyte activating cytokines (IL-1)
t cell growth factors (IL-2, IL-7, IL-9, IL-15)
macrophage activating cytokines (IFN-gamma)

Question 16

cytotoxins

Answer 16

identified as products of activated lymphocytes or macrophages
can kill tumour cells
tumour necrosis factor (TNF) - poor anti-tumour

Question 17

effector molecules for different T cells

Answer 17

cd8 - cytotoxic effector molecules
cd4 th1 - macrophage-activating effector molecules
cd4 th2 - b cell-activating effector molecules

Question 18

cytotoxic effector molecules

Answer 18

released by cd8 t cells 
perforin 
granzymes  
granulysin 
fas ligand

Question 19

macrophage-activating effector molecules

Answer 19

released by cd4 th1 t cells
IFN-gamma
GM-CSF
TNF-alpha 
CD40 ligand 
fas ligand

Question 20

b cell-activating effector molecules

Answer 20

released by cd4 th2 t cells
IL-4
IL-5
IL-15
CD40 ligand

Question 21

other effector molecules released by CD4 Th1 cells

Answer 21

IL-3
TNF-beta
IL-2
CXCL2
GRO beta

Question 22

other effector molecules released by CD4 Th2 cells

Answer 22

IL-3
GM-CSF
IL-10 
TGF-beta
CCL11 (eotaxin)
CCL17

Question 23

effects of IFN-gamma and CD40 ligand

Answer 23

activates macrophage to destroy bacteria

released from activated from th1 cell

Question 24

effects of TNF-alpha

Answer 24

activates endothelium to induce macrophage binding and exit from blood vessel at site of infection
(released from activated from th1 cell)

Question 25

effects of GM-CSF

Answer 25

induces macrophage differentiation in bone marrow

Question 26

immune-stimulating cytokine deficiency

Answer 26

X-linked SCID (severe combined immunodeficiency) | caused by genetic inactivation of one receptor - common signalling component of IL-2, IL-4 and IL-7

Question 27

cardinal signs of inflammation

Answer 27

``` heat swelling redness pain tissue damage most can be explained by biological activation of inflammatory cytokines on vascular endothelium - most through production of prostaglandins or chemokines ```

Question 28

what happens to cause inflammation?

Answer 28

bacteria trigger macrophages to release cytokines and chemokines vasodilation and increased vascular permeability cause redness, heat and swelling inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain

Question 29

TNF-mediated diseases

Answer 29

``` septic shock multiple organ f failure respiratory distress syndrome rheumatoid arthritis inflammatory bowel disease graft-versus-host rejection diabetes ```

Question 30

cytokines in allergy

Answer 30

Th2 cytokines are important

Question 31

what mediators cause Th1 differentiation?

Answer 31

IFN-gamma IL-12 IL-23

Question 32

what mediators cause Th2 differentiation?

Answer 32

IL-4

Question 33

T cell subsets

Answer 33

Th1: IFN-gamma (inflammation) Th2: IL-4, -5, -9, -13 (allergy, anti-inflammation) Th17: IL-17 (inflammation) Treg: IL-10 - inhibits activity of other T cells (anti-inflammation)

Question 34

chemokines

Answer 34

chemotactic cytokines | cause chemotaxis

Question 35

chemotaxis

Answer 35

migration towards a gradient discovered for ability fo neutrophils to chase bacteria explains infiltration of leukocytes - macrophages important in homing and migration of cell of the immune system

Question 36

CCL2 chemokine

Answer 36

released from activated Th1 cell | causes macrophages to accumulate at site of infection

Question 37

therapeutic use of cytokines

Answer 37

``` IFN-gamma: macrophage activation IFN-beta - immunomodulation host defence haematoapoiesis pathogenesis ```

Question 38

cytokines - host defence

Answer 38

IL-2 (melanoma, renal cell carcinoma) | IFN-alpha (hair cell leukaemia, Kaposi, viral hepatitis)

Question 39

cytokines - haematpoeisis

Answer 39

GM-CSF (myeloreconstitution, following bone marrow transplant) G-CSF (chemotherapy-induced neutropenia) IL-11 (thrombocytopenia) EPO (anaemia)

Question 40

pathogenesis

Answer 40

anti-TNF and sTNFR (RA, UC, psoriasis) IL-1Ra (RA, cryopryrin-associated periodic syndromes) anti-IL-6, IL-6R (RA) anti-IL-17,-12-23 (psoriasis, ankylosing spondylitis, Crohn's) anti-IL-5 (asthma, eosinophilic granulomatosis) anti-IL-4R (atopic dermatitis - eczema)