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Principles of Immunology Cytokines
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Cytokines (Greek cyto-, cell; and -kinos, movement) are small cell-signaling protein molecules that are secreted by the cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication. Cytokines can be classified as proteins, peptides, or glycoproteins; the term "cytokine" encompasses a large and diverse family of regulators produced throughout the body by cells of diverse embryological origin.
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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, <30kD
High affinity for receptors Active in picomole amounts
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Chain of Cytokine Action
Stimulus>Cytokine-producing cell> Cytokine>Receptor>Target cell> Biological effect(s)
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Names of Cytokines Source Function Intercellular action
e.g.,Lymphokines(secreted by lymphocyte) Function e.g.,Chemokines(low molecular weight) Intercellular action e.g., Interleukins(secreted by leukocyte)
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Action of Cytokines Autocrine Paracrine Endocrine
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 Redundancy Synergy Antagonism Cascading
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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Redundancy
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Cytokine-generating Cells
Innate immunity Macrophages Endothelial cells Fibroblasts Adaptive immunity T lymphocytes 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
Phosphorylation of tyrosine Binding of STAT(Signal transducers and activators of transcription) Translocation of STAT to cell’s 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
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
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