8. cytokines and chemokines Flashcards
what is a cytokine?
soluble mediator
ligate receptor and trigger a signalling cascade
leads to activated transcription of specific genes
cytokines in haematopoiesis
GM-CSF G-CSF SCF IL-6 IL-5 IL-2 IL-11 EPO TPO \+ others (eg. il-3)
GM-CSF in haematopoiesis
differentiation to : - common myeloid progenitor - mast cell - myeloblast \+ myeloblast offspring: basophil, neutrophil, eosinophil, monocyte
G-CSF in haematopoiesis
differentiation to:
- mast cell
- basophil
- neutrophil
SCF in haematopoiesis
mast cell
IL-6 in haematopoiesis
mast cell
IL-5 in haematopoiesis
eosinophil
IL-2 in haematopoiesis
T lymphocyte
IL-11 in haematopoiesis
megakaryocyte
EPO in haematopoiesis
erythrocyte
TPOin haematopoiesis
megakaryocyte
mediators of host defence
antiviral mediatros (interferons)
immune activators
cytotoxins
interferons
antiviral mediators
products of virus-infected cells
interfere with viral replication
interferon examples
IFN-alpha - made by lymphocytes
IFN-beta - made by fibroblasts
IFN-alpha - made by lymphocytes and NK cells
immune activators
lymphocyte activating cytokines (IL-1)
t cell growth factors (IL-2, IL-7, IL-9, IL-15)
macrophage activating cytokines (IFN-gamma)
cytotoxins
identified as products of activated lymphocytes or macrophages
can kill tumour cells
tumour necrosis factor (TNF) - poor anti-tumour
effector molecules for different T cells
cd8 - cytotoxic effector molecules
cd4 th1 - macrophage-activating effector molecules
cd4 th2 - b cell-activating effector molecules
cytotoxic effector molecules
released by cd8 t cells perforin granzymes granulysin fas ligand
macrophage-activating effector molecules
released by cd4 th1 t cells IFN-gamma GM-CSF TNF-alpha CD40 ligand fas ligand
b cell-activating effector molecules
released by cd4 th2 t cells IL-4 IL-5 IL-15 CD40 ligand
other effector molecules released by CD4 Th1 cells
IL-3 TNF-beta IL-2 CXCL2 GRO beta
other effector molecules released by CD4 Th2 cells
IL-3 GM-CSF IL-10 TGF-beta CCL11 (eotaxin) CCL17
effects of IFN-gamma and CD40 ligand
activates macrophage to destroy bacteria
released from activated from th1 cell
effects of TNF-alpha
activates endothelium to induce macrophage binding and exit from blood vessel at site of infection
(released from activated from th1 cell)
effects of GM-CSF
induces macrophage differentiation in bone marrow
immune-stimulating cytokine deficiency
X-linked SCID (severe combined immunodeficiency)
caused by genetic inactivation of one receptor - common signalling component of IL-2, IL-4 and IL-7
cardinal signs of inflammation
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
what happens to cause inflammation?
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
TNF-mediated diseases
septic shock multiple organ f failure respiratory distress syndrome rheumatoid arthritis inflammatory bowel disease graft-versus-host rejection diabetes
cytokines in allergy
Th2 cytokines are important
what mediators cause Th1 differentiation?
IFN-gamma
IL-12
IL-23
what mediators cause Th2 differentiation?
IL-4
T cell subsets
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)
chemokines
chemotactic cytokines
cause chemotaxis
chemotaxis
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
CCL2 chemokine
released from activated Th1 cell
causes macrophages to accumulate at site of infection
therapeutic use of cytokines
IFN-gamma: macrophage activation IFN-beta - immunomodulation host defence haematoapoiesis pathogenesis
cytokines - host defence
IL-2 (melanoma, renal cell carcinoma)
IFN-alpha (hair cell leukaemia, Kaposi, viral hepatitis)
cytokines - haematpoeisis
GM-CSF (myeloreconstitution, following bone marrow transplant)
G-CSF (chemotherapy-induced neutropenia)
IL-11 (thrombocytopenia)
EPO (anaemia)
pathogenesis
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)
