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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
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 6, 2024, from https://doi.org/10.69645/VSPW3005.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Bruce Beutler has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.