Lecture 28 - Cytokines
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- Words: 997
- Pages: 46
No. Date
TOPIC
TUTOR
1
20.9 The Immune System
Prof. Raj
2
20.9 Organs and Cells of the Immune System
Dr. Raja’a
3
21.9 The Major Histocompatibility Complex
Prof. Raj
4
21.9 Antigens and Antigen Presentation
Prof. Raj
5
22.9 Humoral Immunity
Prof. Raj
6
25.9 Antibody Functions and Complement
Prof. Raj
7
25.9 T cell Receptors & Cell-mediated
Prof. Raj
8
27.9 Cell-mediated Immunity
Prof. Raj
9
27.9 Cytokines
Prof. Raj
Immunity
What are Cytokines ? Cytokines are low-molecular-weight regulatory proteins secreted by white blood cells and various other cells in response to a number of stimuli. Cytokines are soluble proteins secreted by one cell that can alter the behaviour or properties of the same cell or of another cell.
Properties of Cytokines - 7 Cytokines can network
Inflammation
Endothelial cells
Fibroblasts
Hematopoiesis
Stem cells Macrophage
Mast cell
Neutrophil Eosinophil
T helper cell
NK cell
B cell LAK cell
Plasma cells Antibodies
Cytotoxic T cell
What are Cytokines ? Secreted molecules that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells Cytokines = messengers of the immune system, just as hormones = messengers of the endocrine system
Cytokines by any other name…. Lymphokines – cytokines secreted by lymphocytes Monokines – cytokines secreted by monocytes/macrophages Interleukins – secreted by leukocytes, act on leukocytes Chemokines – cytokines that are chemotactic and play important roles in inflammation
Interferons, CSFs, tumor necrosis factors etc
Properties of Cytokines
Properties of Cytokines - 1 Inducing stimulus
Cytokines Cytokine receptor
Biological effects Cytokines bind to specific receptors on target cell membranes, trigger signal-transduction pathways and alter gene expression
Properties of Cytokines – 2
Autocrine action
Paracrine action
Endocrine action
Nearby cell
Circulation
Distant cell
Properties of Cytokines - 3 A single cytokine can have different effects
Properties of Cytokines - 3 A single cytokine can have different effects Activation Proliferation Differentiation B cells Proliferation
IL- 4
T cell
Thymocyte
Proliferation Mast cell
Properties of Cytokines - 4 Different cytokines can have the same effect
Properties of Cytokines - 4 Different cytokines can have the same effect
IL-2 IL-4 IL-5 T cell
Proliferation B cell
Properties of Cytokines - 5 Cytokines can work in synergy
Properties of Cytokines - 5 Cytokines can work in synergy
T cell
IL- 4 + IL-5
Class switch B cell
to IgE
Properties of Cytokines – 6 The effect of one cytokine can inhibit another
Properties of Cytokines – 6 The effect of one cytokine can inhibit another
IL-4 T cell
IFNγ
IL-4 switch to IgE IFNγ blocks switch B cell
Properties of Cytokines - 7 Cytokines can network
Properties of Cytokines - 7 Cytokines can network IFNγ T cell
Macrophage
IL-12 IFNγ, TNF, IL-2 etc T cell
Properties of Cytokines - 7 Cytokines can network
Inflammation
Endothelial cells
Fibroblasts
Hematopoiesis
Stem cells Macrophage
Mast cell
Neutrophil Eosinophil
T helper cell
NK cell
B cell LAK cell
Plasma cells Antibodies
Cytotoxic T cell
General Functions of Cytokines Intercellular messenger molecules •
Development of cellular & humoral responses
•
Induction of inflammatory responses
•
Regulation of hematopoiesis
•
Cellular proliferation and differentiation
•
Growth inhibition, apoptosis
•
Wound healing
T cells CD4+ (Th)
Th1 (Type 1)
CD8+ (Tc)
Th2 (Type 2)
Ags are Internalized, Processed and Presented by APC MHC+Epitope complex is recognized by T cells Specific T cells become activated
Th2 cells
HELP for B cells
B cells produce antibodies
Th1 cells
HELP for T cells
T cells activate other T cells and macrophages
Th1 and Th2 cells Th1: IFNγ, TNFβ, TNFα, IL-2
Th2: IL-4, IL-5, IL-9, IL-10, IL-13
Th1 and Th2 cells Th1: IFNγ, TNFβ, TNFα, IL-2 Mφ activation, CTL activation, DTH
Th2: IL-4, IL-5, IL-9, IL-10, IL-13 Most IgG subclasses IgE IgA (mucosal immunity) Eosinophil stimulation
HI
CMI
Th1 and Th2 cells Th1 cells - Cell-mediated inflammatory reactions, - Interact with mononuclear cells & help them eliminate intracellular pathogens - CMI
Th2 cells – Strong humoral and allergic reactions, - Interact with B cells and cause B cell activation, division and differentiation - HI
Cytokine
Sources
Targets
Effects
IL-1
APC
Th, B cells, Macs, Neutros
Activation Chemotaxis
IL-2
Th1
Th, Tc
Proliferation
IL-1
IL-2 Cytokines
APC
Resting T
Activated T
HELP !
Cytokine
Sources
IL-4
Th2
IL-6
Th2, Monos, Macrophages
IL-10
Th2
Targets
Effects
Resting B cells Activated B
Activation Proliferation
Activated B cells
Differentiation into AFC
B cells Macrophages
Differentiation Suppresses Th1
Induction of Humoral Immunity
B
1. Activation
APC
2. Division 3. Differentiation
IL-1
Activation
IL-4
Th
B IL-2 IL-4 IL-5
Division
B
B IL-4 IL-6 IL-10 IFNγ
Differentiation
AFC
AFC
Cytokine
Sources
Targets
Effects
IFNγ
Th1, Tc, NK
Proliferating B Macrophages Th2
Differentiation Enhances activity Inhibits prolif.
TNFα
Macrophages
Tumor cells Inflamm. cells
Cytotoxic Inflammation
TNFβ
Th1, Tc
Target cells
Cytotoxicity
Perforin
Enzymes
Cytokines
Cytokine
Sources
Targets
IL-1
APC
Th, B cells, Macs, Neutros
Activation Chemotaxis
IL-2
Th1
Th, Tc
Proliferation
IL-4
Th2
IL-6
Th2, Monos, Macrophages
Resting B cells Activated B cells Activated B cells
Activation Proliferation Differentiation into AFC
IL-10
Th2
IFNγ
Th1, Tc, NK
Proliferating B Macrophages Th2
Differentiation Enhances activity Inhibits prolif.
TNFα
Macrophages
TNFβ
Th1, Tc
Tumor cells Inflamm. cells Target cells
Cytotoxic Inflammation Cytotoxicity
B cells Macrophages
Effects
Differentiation Suppresses Th1
What are Cytokines ? Cytokines are low-molecular-weight regulatory proteins secreted by white blood cells and various other cells in response to a number of stimuli. Cytokines are soluble proteins secreted by one cell that can alter the behaviour or properties of the same cell or of another cell.
What are Cytokines ? Secreted molecules that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells Cytokines = messengers of the immune system, just as hormones = messengers of the endocrine system
Exaggerated Response against harmless foreigner
Hypersensitivity, allergy !
No attack on “self”, accepting “self”
Immunological Tolerance!
Attack on “self”
Autoimmunity
Poor defense systems
Immunodeficiency
1 2
4
3
TOPIC
TUTOR
1
20.9 The Immune System
Prof. Raj
2
20.9 Organs and Cells of the Immune System
Dr. Raja’a
3
21.9 The Major Histocompatibility Complex
Prof. Raj
4
21.9 Antigens and Antigen Presentation
Prof. Raj
5
22.9 Humoral Immunity
Prof. Raj
6
25.9 Antibody Functions and Complement
Prof. Raj
7
25.9 T cell Receptors & Cell-mediated
Prof. Raj
8
27.9 Cell-mediated Immunity
Prof. Raj
9
27.9 Cytokines
Prof. Raj
Immunity
What are Cytokines ? Cytokines are low-molecular-weight regulatory proteins secreted by white blood cells and various other cells in response to a number of stimuli. Cytokines are soluble proteins secreted by one cell that can alter the behaviour or properties of the same cell or of another cell.
Properties of Cytokines - 7 Cytokines can network
Inflammation
Endothelial cells
Fibroblasts
Hematopoiesis
Stem cells Macrophage
Mast cell
Neutrophil Eosinophil
T helper cell
NK cell
B cell LAK cell
Plasma cells Antibodies
Cytotoxic T cell
What are Cytokines ? Secreted molecules that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells Cytokines = messengers of the immune system, just as hormones = messengers of the endocrine system
Cytokines by any other name…. Lymphokines – cytokines secreted by lymphocytes Monokines – cytokines secreted by monocytes/macrophages Interleukins – secreted by leukocytes, act on leukocytes Chemokines – cytokines that are chemotactic and play important roles in inflammation
Interferons, CSFs, tumor necrosis factors etc
Properties of Cytokines
Properties of Cytokines - 1 Inducing stimulus
Cytokines Cytokine receptor
Biological effects Cytokines bind to specific receptors on target cell membranes, trigger signal-transduction pathways and alter gene expression
Properties of Cytokines – 2
Autocrine action
Paracrine action
Endocrine action
Nearby cell
Circulation
Distant cell
Properties of Cytokines - 3 A single cytokine can have different effects
Properties of Cytokines - 3 A single cytokine can have different effects Activation Proliferation Differentiation B cells Proliferation
IL- 4
T cell
Thymocyte
Proliferation Mast cell
Properties of Cytokines - 4 Different cytokines can have the same effect
Properties of Cytokines - 4 Different cytokines can have the same effect
IL-2 IL-4 IL-5 T cell
Proliferation B cell
Properties of Cytokines - 5 Cytokines can work in synergy
Properties of Cytokines - 5 Cytokines can work in synergy
T cell
IL- 4 + IL-5
Class switch B cell
to IgE
Properties of Cytokines – 6 The effect of one cytokine can inhibit another
Properties of Cytokines – 6 The effect of one cytokine can inhibit another
IL-4 T cell
IFNγ
IL-4 switch to IgE IFNγ blocks switch B cell
Properties of Cytokines - 7 Cytokines can network
Properties of Cytokines - 7 Cytokines can network IFNγ T cell
Macrophage
IL-12 IFNγ, TNF, IL-2 etc T cell
Properties of Cytokines - 7 Cytokines can network
Inflammation
Endothelial cells
Fibroblasts
Hematopoiesis
Stem cells Macrophage
Mast cell
Neutrophil Eosinophil
T helper cell
NK cell
B cell LAK cell
Plasma cells Antibodies
Cytotoxic T cell
General Functions of Cytokines Intercellular messenger molecules •
Development of cellular & humoral responses
•
Induction of inflammatory responses
•
Regulation of hematopoiesis
•
Cellular proliferation and differentiation
•
Growth inhibition, apoptosis
•
Wound healing
T cells CD4+ (Th)
Th1 (Type 1)
CD8+ (Tc)
Th2 (Type 2)
Ags are Internalized, Processed and Presented by APC MHC+Epitope complex is recognized by T cells Specific T cells become activated
Th2 cells
HELP for B cells
B cells produce antibodies
Th1 cells
HELP for T cells
T cells activate other T cells and macrophages
Th1 and Th2 cells Th1: IFNγ, TNFβ, TNFα, IL-2
Th2: IL-4, IL-5, IL-9, IL-10, IL-13
Th1 and Th2 cells Th1: IFNγ, TNFβ, TNFα, IL-2 Mφ activation, CTL activation, DTH
Th2: IL-4, IL-5, IL-9, IL-10, IL-13 Most IgG subclasses IgE IgA (mucosal immunity) Eosinophil stimulation
HI
CMI
Th1 and Th2 cells Th1 cells - Cell-mediated inflammatory reactions, - Interact with mononuclear cells & help them eliminate intracellular pathogens - CMI
Th2 cells – Strong humoral and allergic reactions, - Interact with B cells and cause B cell activation, division and differentiation - HI
Cytokine
Sources
Targets
Effects
IL-1
APC
Th, B cells, Macs, Neutros
Activation Chemotaxis
IL-2
Th1
Th, Tc
Proliferation
IL-1
IL-2 Cytokines
APC
Resting T
Activated T
HELP !
Cytokine
Sources
IL-4
Th2
IL-6
Th2, Monos, Macrophages
IL-10
Th2
Targets
Effects
Resting B cells Activated B
Activation Proliferation
Activated B cells
Differentiation into AFC
B cells Macrophages
Differentiation Suppresses Th1
Induction of Humoral Immunity
B
1. Activation
APC
2. Division 3. Differentiation
IL-1
Activation
IL-4
Th
B IL-2 IL-4 IL-5
Division
B
B IL-4 IL-6 IL-10 IFNγ
Differentiation
AFC
AFC
Cytokine
Sources
Targets
Effects
IFNγ
Th1, Tc, NK
Proliferating B Macrophages Th2
Differentiation Enhances activity Inhibits prolif.
TNFα
Macrophages
Tumor cells Inflamm. cells
Cytotoxic Inflammation
TNFβ
Th1, Tc
Target cells
Cytotoxicity
Perforin
Enzymes
Cytokines
Cytokine
Sources
Targets
IL-1
APC
Th, B cells, Macs, Neutros
Activation Chemotaxis
IL-2
Th1
Th, Tc
Proliferation
IL-4
Th2
IL-6
Th2, Monos, Macrophages
Resting B cells Activated B cells Activated B cells
Activation Proliferation Differentiation into AFC
IL-10
Th2
IFNγ
Th1, Tc, NK
Proliferating B Macrophages Th2
Differentiation Enhances activity Inhibits prolif.
TNFα
Macrophages
TNFβ
Th1, Tc
Tumor cells Inflamm. cells Target cells
Cytotoxic Inflammation Cytotoxicity
B cells Macrophages
Effects
Differentiation Suppresses Th1
What are Cytokines ? Cytokines are low-molecular-weight regulatory proteins secreted by white blood cells and various other cells in response to a number of stimuli. Cytokines are soluble proteins secreted by one cell that can alter the behaviour or properties of the same cell or of another cell.
What are Cytokines ? Secreted molecules that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells Cytokines = messengers of the immune system, just as hormones = messengers of the endocrine system
Exaggerated Response against harmless foreigner
Hypersensitivity, allergy !
No attack on “self”, accepting “self”
Immunological Tolerance!
Attack on “self”
Autoimmunity
Poor defense systems
Immunodeficiency
1 2
4
3
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