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Unformatted text preview: Immunology 6: Inflammation: Recruitment, Chemotaxis and Phagocytosis Macrophages and dendritic cells activated by pathogens secrete a range of cytokines that have a variety of local and distant effects Cytokines are small proteins that induce responses through binding to specific receptors Autocrine= affect behaviour of cell that releases the cytokine, paracrine= affecting behaviour of adjacent cells , endocrine= affecting behaviour of distance cells (depends on ability to enter circulation and on their half-life in blood) Activation of pathogen-sensing receptors expressed by macrophages and DCs induces the production of specific cytokines that activate the cellular arm of the innate immune response 2 classes of dendritic cells: 1. Conventional= participate most directly in antigen presentation and activation of naive cells 2. Plasmacytoid= distinct cell lineage that produces large amounts of interferon, in response to viral infections but may not be as important for activating naive T cells Immature DCs= are phagocytic but can be distinguished from macrophages by their expression of different surface molecules Interleukin= molecules secreted by, and acting on, leukocytes Cytokines can be grouped by structure into different families IL-1= 11 members= most are produced as inactive proteins that are cleaved to produce the mature cytokine( remove amino-terminal peptide); IL-1B and IL-18 are produced by macrophages in response to TLR signalling, are cleaved by caspase 1; IL-1 family receptors= have TIR domains in their cytoplasmic tails and signal by the NKkB pathway Hematopoietin superfamily= non-immune system growth and differentiation factors ( erythropoietin and growth hormone) as well as interleukins with roles in innate and adaptive immunity; IL-6 and cytokine GM-CSF (stimulates production of new monocytes and granulocytes in bone marrow)= act through dimeric receptors = signal through the JAK-STAT pathwayone chain confers specificity and the other confers the intracellular signalling Interferon receptors= small family of heterodimeric reptors that recognize type I interferon as well as some cytokines (IL 4 produced by T cells)= signal through JAK-STAT pathway and activate different combinations of STATs with different effects TNF family=TNF-a is the prototype= more than 17 cytokines with important functions in adaptive and innate immunity= transmembrane proteins = gives them distinct properties and limits their range of action= usually found as homotrimers of a membrane-bound subunitTNF-a is initially expressed as a trimeric-membrane bound cytokine but can be released from the membrane= effects are mediated by TNFR-I( endothelial cells and macrophages) and TNFR-II receptors(lymphocytes) Cytokines and receptors have diversified in parallel= contribute to both innate and adaptive immune responses See previous lecture for important cytokines and chemokines secreted by macrophages and DCs in response to bacterial products...
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- Spring '11