Principles of Immunology Cytokines 2/2/06

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Principles of ImmunologyCytokines2/2/06

• Live simply so others can simply live.
• Anonymous

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Word List

• Autocrine
• Endocrine
• Immunoglobulin superfamily
• Interleukin
• Paracrine
• Pleiotropy
• Stem cell factor

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Chemical Structure

• Low molecular weight proteins, lt30kD
• High affinity for receptors
• Active in picomole amounts

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Chain of Cytokine Action

• StimulusgtCytokine-producing cellgt
• CytokinegtTarget cellgtReceptorgt
• Biological effect(s)

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Names of Cytokines

• Source
• e.g.,Lymphokines
• Function
• e.g.,Chemokines
• Intercellular action
• e.g., Interleukins

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Action of Cytokines

• Autocrine
• Affects the generating cell (self)
• Paracrine
• Affects cells in the immediate vicinity
• Endocrine
• Affects cells remote from the secreting cell

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Action of Cytokines

• Pleiotropy
• Affects multiple cell types
• Redundancy
• Multiple cytokines affects cells of the same type
• Synergy
• Cytokines acting in concert on the same cell
• Antagonism
• Competing actions
• Cascading
• Cytokines acting sequentially

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Cytokine-generating Cells

• Innate immunity
• Macrophages
• Endothelial cells
• Fibroblasts
• Adaptive immunity
• T lymphocytes
• Macrophages
• NK cells

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Cytokine Receptors

• Ig super family
• Class I- hematopoietin
• Class II-interferon
• TNF
• Chemokine

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Cytokine Receptors

• Multimeric receptors
• Common signal-transducing subunits
• Unique high affinity subunits
• High affinity subunits associated with activation
  of target cell

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Signal Transduction

• Initiated by cytokine binding
• Activates JAK (Janus kinase)
• Phosphorylation of tyrosine
• Binding of STAT(Signal transducers and activators
  of transcription)
• Translocation of STAT to cells DNA
• Transcription of specific target genes

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Role of Cytokines in Hematopoiesis

• SCF (Stem cell factor)
• GM-CSF (Granulocyte-macrophage colony-stimulating
  factor)
• IL-3 (Interleukin 3)
• IL-5 (Interleukin 5)
• IL-7 (Interleukin 7)
• IL-11(Interleukin 11)

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Cytokines in the Immune Response

• Innate immune response
• IL 1-(Macrophage)-fever, capillary effects
• IL 6-(Macrophage)-adaptive immunity via B cells
• IL 12(Macrophage)-adaptive immunity via T helper
  cells
• TNF (Macrophage)-capillary effects, activates
  neutrophils
• IFN alpha (Macrophage)-multiple effects
• IFN beta (Fibroblasts)-multiple effects

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Cytokines in the Immune Response

• Adaptive immune response
• IL 2-(T cells)-multiple effects)
• IL 4-(T cells mast cells)-T cell
  differentiation, IgE production
• TGF beta (T cells, macrophages)-inhibits
  adaptive immune response
• IFN gamma-(T cells, NK cells)-Macrophage
  activation

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Subsets of T helper Cells

• T helper 1
• IgG production/Complement fixation
• Macrophage activation
• DTH
• CTL production
• T helper 2
• IgE production
• Eosinophils

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• Cytokine antagonism and viral diseases
• Using cytokines therapeutically