Chemokines and cytokines Flashcards
Mechanism of all cytokines
Triggers two receptor subunits to ligate
- Sends a signalling cascade to activate transcription of genes
Cytokines important for common myeloid progenitor differentiation
GM-CSF
Cytokines important for mast cell differentiation
GM-CSF
SCF
G-CSF
IL-6
Important cytokines in hematopoiesis
GM-CSF
SCF
G-CSF
IL-2, IL-6, IL-11, IL-5
EPO
TPO
Important cytokines in T cell differentiation
IL-2
Inteferons
- IFN-a
- IFN-b
- IFN-g
Interferes with viral infection
IFN-a
- made by Lymphocytes
IFN-b
- made by fibroblasts
IFN-g
- Poor antiviral
- Made by lymphocytes and NK cells
Immune activators:
- Lymphocyte activating cytokines
- T cell growth factors
- Macrophage activating cytokines
Lymphocyte activating cytokines
- IL-1
T cell growth factors
- IL-2
Macrophage activating cytokines
- IFN-gamma
- TNF-alpha
Cytotoxins
Products of activated lymphocytes or macrophages
- Can kill tumour cells
Includes
- TNF-alpha.
TNF was tested as a potential anti-cancer agent but was too toxic.
B cell activating molecules [4]
Secreted by Th2 cells:
IL-4
IL-5
IL-10
TGF-beta
TH1 cells
Type of CD4 helper cell.
Secretes macrophage activating effector molecules:
- IFN-gamma
- TNF-alpha
- CD40 ligand
Other cytokines secreted:
- Fas ligand
- IL-2
- IL-3, GM-CSF
Cytokines are important for inflammation
TH2 cells
Type of CD4 helper cell.
Secretes B-cell activating effector molecules.
SCID
Severe combined immunodeficiency
- X-linked: genetic inactivation of a receptor
The receptor is involved in the signalling of:
- IL-2 (required for T-cell growth/ differentiation)
- IL-4 (Required for B cell activation)
- IL-7 (T cell growth factor)
Cachexia and cytokines
Activated macrophages produces TNF which induces cachexia through inflammation.
Cardinal signs of inflammation
Heat
Swelling
Pain
Redness
Tissue damage/ loss of function
Mechanism of inflammation
Inflammatory cytokines released act on the vascular endothelium.
- Increases vascular permeability–> red, heat, swelling.
Also production of prostaglandins and chemokines.–> migration of inflammatory cells, to release inflammatory mediators= pain
TNF mediated diseases
Rheumatoid arthritis
Inflammatory bowel disease
Also:
- Septic shock
- Diabetes
- Graft vs host rejection
- Pulmonary fibrosis
Cytokines and allergies
Mainly mediated by Th2 cells
- Releases IL-4, 5 , 9 and 13.
Th17
T cell subset involved in inflammation
- Secretes IL-17.
Treg cells
Regulatory cells
- Secreted anti-inflammatory molecules: IL-10= inhibits activity of other cells.
Chemokines
Stimulate the migration of cells towards a gradient (chemotaxis)
MCP-1
Monocyte chemoattractant protein-1
- Also called Chemokine (C-C motif) 2, CCL2
Causes macrophages to accumulate at the site of infection.
IL-8
Chemokine produced by macrophages, epithelial cells, endothelial cells, smooth muscle airway cells.
- Acts on CXCR1 receptor
Primarily induces neutrophils into the site of infection.
Therapeutic use of IFN-beta
Used to treat Multiple sclerosis
- Immunomodulation: reduces the amount of relapse attacks
Works by balancing pro and anti-inflammatory markers in the brain + reducing inflammatory cells in blood brain barrier
Therapeutic use of IL-2
Melanoma
Renal cell carcinoma
