HTHSCI 1DT3 Lecture Notes - Lecture 17: Monocyte, Reverse Transcriptase, Proteasome

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1) Initiator and innate cytokines
IFN-alpha/beta
There is one IFN-beta and multiple IFN-alpha genes
Mostly made by cells in response to viral infection
Stimulates specific expressions of Interferon Specific Genes (ISGs), of which there are 100s the
functions of which are variably understood!
Activate NK cell cytotoxicity, enhance MHC 1 antigen presentation, facilitate T-cel IFN responses
TNF-alpha
Upregulate MHC class 1, activate antiviral and immunoregulatory pathways, stimulate cell proliferation
and anti-apoptotic factors, stimulates liver cells to produce c-reactive protein
2) Adaptive cytokines
= produced mainly, or exclusively, by T cells
IL2: an autocrine growth factor causing T cell proliferation (T cell express IL-2 receptors); induces IFN-
gamma expression
IFN-gamma: enhance antigen processing and MHC presentation, induces isotype switching and
stimulates NO synthase
3) Chemokines
= are chemotactic cytokines of 8-12kd in size (i.e. smaller than other cytokines)
four families exist: C (have one disulphide bridge), CC (2 disulphide bridges), C-X-C (2 disulphide
bridges separated by any amino acid), C-X3-C (2 disulphide bridges separated by any three
amino acids)
chemokines are a homing beacon for cell migration; chemokine concentration increases with
the direction of chemotaxis
CCL3 (macrophage inflammatory protein)
induces the synthesis and release of other pro-inflammatory cytokines like IL-1, IL-6 and TNF-
alpha from fibroblasts and macrophages
induces migration of protective NK cells into CMV infected liver (an innate function)
causes tissue inflammation in influenza, HSV and coxsackie infections
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Document Summary

There is one ifn-beta and multiple ifn-alpha genes. Mostly made by cells in response to viral infection. Stimulates specific expressions of interferon specific genes (isgs), of which there are 100s the functions of which are variably understood! Activate nk cell cytotoxicity, enhance mhc 1 antigen presentation, facilitate t-cel ifn responses. Upregulate mhc class 1, activate antiviral and immunoregulatory pathways, stimulate cell proliferation and anti-apoptotic factors, stimulates liver cells to produce c-reactive protein: adaptive cytokines. = produced mainly, or exclusively, by t cells. Il2: an autocrine growth factor causing t cell proliferation (t cell express il-2 receptors); induces ifn- gamma expression. Ifn-gamma: enhance antigen processing and mhc presentation, induces isotype switching and stimulates no synthase: chemokines. Currently 13 which recognise different pamps (see above) Role in viral recognition on the endosomal membrane, triggering ifn production: ss-hcv rna triggers tlr7/8, activating the myd88 adaptor protein irf7 ifn-alpha ds-hcv rna triggers tlr3, activating the trif adaptor protein irf3 ifna-beta.

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