Lecture 17 Cytokines
Lecture 17 Cytokines
What are cytokines? A collection of polypeptides used for communications between cells Play role similar to hormones(messengers of the endocrine system) Hormones usually act at a distance Cytokines act locally Differ from growth factors that are produced constitutively,while cytokine production is carefully regulated Play an important role in both innate and adaptive immunity
What are cytokines? ◼ A collection of polypeptides used for communications between cells ◼ Play role similar to hormones (messengers of the endocrine system) ◼ Hormones usually act at a distance ◼ Cytokines act locally ◼ Differ from growth factors that are produced constitutively, while cytokine production is carefully regulated ◼ Play an important role in both innate and adaptive immunity
Cytokine nomenclature Interleukins (1-18) Interferons(a,β，Y) Others (common names)
Cytokine nomenclature ◼ Interleukins (1-18) ◼ Interferons (a,b,g) ◼ Others (common names)
Cytokine -mediated effects Cell growth Cell differentiation Cell death Induce non-responsiveness to other cytokines/cells Induce responsiveness to other cytokines/cells Induce secretion of other cytokines
Cytokine -mediated effects ◼ Cell growth ◼ Cell differentiation ◼ Cell death ◼ Induce non-responsiveness to other cytokines/cells ◼ Induce responsiveness to other cytokines/cells ◼ Induce secretion of other cytokines
How do cytokines tell cells what to do? Produced by cells as part of normal cellular activity and/or the result of environmental trigger Bind to receptors on cells Trigger signal transduction pathways Initiate synthesis of new proteins
How do cytokines tell cells what to do? ◼ Produced by cells as part of normal cellular activity and/or the result of environmental trigger ◼ Bind to receptors on cells ◼ Trigger signal transduction pathways ◼ Initiate synthesis of new proteins
Properties of cytokines Proteins Low molecular weight 口 Bind to receptor on either cell which produced it or another cell Receptor binding triggers a signal Signal results in altered pattern of gene expression
Properties of cytokines ◼ Proteins ◼ Low molecular weight ◼ Bind to receptor on either cell which produced it or another cell ◼ Receptor binding triggers a signal ◼ Signal results in altered pattern of gene expression
Cytokines can act in three different manners Autocrine Cytokine binds to receptor on cell that secreted it Paracrine Cytokine binds to receptors on near by cells Endocrine Cytokine binds cells in distant parts of the body
Cytokines can act in three different manners ◼ Autocrine ◼ Cytokine binds to receptor on cell that secreted it ◼ Paracrine ◼ Cytokine binds to receptors on near by cells ◼ Endocrine ◼ Cytokine binds cells in distant parts of the body
Cytokine Actions Pleiotropy Act on more than one cell type (INFa/B) Redundancy More than one cytokine can do the same thing (IFNo/βand IFNy) 口 Synergy Two or more cytokines cooperate to produce an effect that is different or greater than the combined effect of the two cytokines when functioning separately (IL-12 and IL-8) Antagonism Two or more cytokines work against each other (IL-4 and IL-12)
Cytokine Actions ◼ Pleiotropy ◼ Act on more than one cell type (INFa/b) ◼ Redundancy ◼ More than one cytokine can do the same thing (IFNa/b and IFNg) ◼ Synergy ◼ Two or more cytokines cooperate to produce an effect that is different or greater than the combined effect of the two cytokines when functioning separately (IL-12 and IL-8) ◼ Antagonism ◼ Two or more cytokines work against each other (IL-4 and IL-12)
How can non-specific cytokines act specifically? Only cells expressing receptors for specific cytokines can be activated by them Many cytokines have very short half-lives Only cells in close proximity will be activated High concentrations of cytokines are needed for activation Only cells in close proximity will be activated May require cell-to cell contact
How can non-specific cytokines act specifically? ◼ Only cells expressing receptors for specific cytokines can be activated by them ◼ Many cytokines have very short half-lives ◼ Only cells in close proximity will be activated ◼ High concentrations of cytokines are needed for activation ◼ Only cells in close proximity will be activated ◼ May require cell-to cell contact
Five cytokine receptor families Immunoglobulin superfamily receptors Class I cytokine receptor family (hematopoietin receptors) Binds most of the cytokines in the immune and hematopoietin systems Class II cytokine receptor family TNF receptor family Chemokine receptor family
Five cytokine receptor families ◼ Immunoglobulin superfamily receptors ◼ Class I cytokine receptor family (hematopoietin receptors) ◼ Binds most of the cytokines in the immune and hematopoietin systems ◼ Class II cytokine receptor family ◼ TNF receptor family ◼ Chemokine receptor family