Share these talks and lectures with your colleagues
Invite colleaguesWe noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo talk
This is a limited length demo talk; you may
login
or review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Innate immune sensing and response
- How do we know when we have an infection?
- The Pfeiffer phenomenon
- LPS is an activator of innate immune response
- Biological phenomenon
- The C3H/HeJ mouse and the Lps locus
- C3H/HeJ mice have a missense mutation of Tlr4
- The "Dorsal group" in drosophila (1)
- The "Dorsal group" in drosophila (2)
- Chronology
- TLR family
- Signaling by the TLR family (1)
- Signaling by the TLR family (2)
- Forward genetics with ENU
- Snowflake
- Velvet
- Piglet
- Eel
- Business class
- Mask
- Results to date
- Positional cloning no longer requires fine mapping
- Positional cloning scheme
- A search for TLR signaling defects
- This has led to these identifications
- MyD88 independent signaling pathway
- Mutations in the TLR signaling pathway
- Spin phenotype (1)
- Spin phenotype (2)
- Spin macrophages produce normal amount of TNF
- A Myd88 mutation fully suppress spin phenotype
- Spin homozygotes develop autoimmunity
- Germfree environment suppress autoimmunity
- Spin is a missense allele of Ptpn6
- Finding the role of SHP1 phosphatase (1)
- Finding the role of SHP1 phosphatase (1)
- Sensing is necessary but not the whole story
- MCMV dose: lethality relationship over time
- How many genes make a life-or-death difference
- MCMV resistance: pathways for survival
- Grey mutant mice
- Genes involved in MCMV resistance (1)
- MCMV-induced cytokines peak timings
- Viral titres of Mayday mutants infected with MCMV
- MayDay is hypersensitive to LPS
- MayDay respond normally to TLR agonists
- MayDay mutation is mapped to chromosome 6
- 2 candidate genes in the MayDay critical region
- The transmembrane topology of SUR2 and Kir6.1
- Absence of Kir6.1 transcripts in MayDay mutants
- LPS-perturbed gene expression in MayDay mice
- Cardiac ischemia in Kir6.1-KO mice
- dSUR plays a protective role against FHV
- Linking endotoxemia to vasoconstriction
- What causes the lethal effect of LPS in MayDay?
- Genes involved in MCMV resistance (2)
- Additional mutations
- Some points about innate immunity
Topics Covered
- Sensing infection is essential to the initiation of an immune response
- The innate immune system senses signature molecules made by microbes using a conserved set of germline-encoded receptors
- This receptor family (the Toll-like receptors) was first understood when a mutation that abolished lipopolysaccharide (LPS) sensing was positionally cloned in mice
- In Drosophila a homologous receptor is also used to detect infection, and still another receptor activates a pathway evocative of the tumor necrosis factor (TNF) pathway in mammals
- Further work in mammals has depended upon gene targeting and also forward genetic work, which has revealed many of the components of the TLR signaling apparatus
- Forward genetics has also allowed us to see how many genes (and what kinds of genes) are important for resisting an infection in vivo
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Beutler, B. (2009, May 31). Innate immune sensing and response [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 15, 2019, from https://hstalks.com/bs/1281/.Publication History
Financial Disclosures
- Prof. Bruce Beutler has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Innate immune sensing and response
Published on May 31, 2009
62 min