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3. Characterization of C3H/HeJ mice, cont\'d. A third specific defect in the mac

ID: 191612 • Letter: 3

Question

3. Characterization of C3H/HeJ mice, cont'd. A third specific defect in the macrophages of C3H/HeJ mice was reported by the immunologist Bruce Beutler and colleagues in 1986 (Beutler et al Science 232:977-980), and related to the production of a molecule initially named cachectin, and later renamed TNF- (tumor necrosis factor-alpha). 31. Cachectin got its name from its ability to cause cachexia when injected into rabbits. What does cachexia mean, and what infectious disease is characterized by this LPS - 3m. What procedure is used in the experiment shown at right to quantify the production of cachectin/TNF by LPS-stimulated macrophages? 3n. What is the key reagent required to perform the assay/procedure you named in (3m)? Figure 2D. Measurement of immune- eaclive cachectin secreled by C3H/HeN and C3H/HeJ peritoneal macrophages. Medium was harvested from macrophage cultures 8 hours following stimulation with 100 ng/mL LPS, then subjected to immunoblot analysis. Arrow indicates position of the immunoreactive cachectin band. 3o. What is the main finding from this figure? 3p. Bruce Beutler hypothesized that C3H/HeJ mice were defective for an unknown gene encoding a receptor that recognized LPS, and his lab devoted years and years to trying to discover this hypothetical gene, which they named Lps. His group had narrowed the location of the mouse Lps gene (mapped it) to a subregion of chromosome 4, but progress was slow, and by 1996 they still had not identified a gene that was mutated in the C3H/HeJ mutant mouse strain. Their work was given a significant boost by a paper published in 1996 by Lemaitre, Hoffiman and colleagues (Cell 86:973-83) that showed a role for a Toll protein in innate immunity. In which organism was Lemaitre/Hoffmann's discovery made? 3q. Does this organism (used by Lemaitre/Hoffmann) have an innate and adaptive immune system, or innate 3r. Inspired by the Lemaitre/Hoffmann results, Beutler's team refined their search. What gene did Poltorak 3s. The 2011 Nobel Prize in Physiology or Medicine was shared by 3 men. Who were they, and what immune system only? and Beutler find was mutated in the C3H/HeJ mice, as reported in 1998 Science 282:2085-8? contributions of each of them was honored by this prize?

Explanation / Answer

3l.Cachexia is a loss of weight.cachexia is calleda s a wasting syndrome as weight loss is prominent also, weakness, loss of appetite and fatigue are observed.

It is also observed in tuberculosis, chronic obstructive diseases, cancer and AIDS like infectious disorders.

3m. the procedure used in present experiment is western blot analysis.

3n. lipopolysachharide mediated macrophage medium is a key reagent required in this experiment.

3o. the result indicated that C3H/HeN reacts with the antibody and recognized by LPS media. Where C3H/HeJ is fails to do so.

3p. drosophila

3q drosophila used in experiment had innate immune system because TOLL and IL-1 are the component of innate immune system.

3r poltorak and bautler finds LPS gene was mutated in mice.

3s. noble prize in medicine or physiology in 2011 shared by : Bruce Beutler, Jules Holffmann, Ralph Steinman.

The noble prize contribution by beutler and holffmann for their discovery concerning activation of innate immune system and Steinman contributed for his discovery of dendrictic cell and it’s role in adaptive immunity.

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