Passage
Lipopolysaccharides (LPS) found in gram-negative bacterial cells can elicit a lethal degree of adjuvanticity, or immune activation, in LPS-responsive host organisms. In mice, responses may be modulated by abnormalities in the toll-like receptor (TLR) encoded by the Tlr4 gene closely linked to coat color on Chromosome 4. To investigate the effect of a particular Tlr4 mutation on LPS response, three experiments were performed following a cross between fully responsive He-N mice [tlr4(+) /tlr4(+) ] and He-J mice homozygous for the mutation [tlr4(d) /tlr4(d) ].Experiment 1Researchers isolated spleen cells for analysis of protein expression and LPS response. In cells isolated from F1 mice, both wild-type and mutant TLRs were distinguishable by protein electrophoresis. Following this first analysis, spleen cells from each cohort were exposed to 2 × 10⁵ SRC, an antigen formed by sheep erythrocytes. Cultures were then incubated in the presence or absence of Ph-LPS, with LPS extracted from Escherichia coli K345 cells using a phenol-water mixture. Titers of anti-SRC antibody were recorded on incubation day 5, with the results shown in Table 1.Table 1 Mean anti-SRC titers with standard error
Experiment 2Serum samples were assayed for interferon production 2 hours post LPS injection. Interferon was quantified using a plaque reduction assay on mouse cells challenged with vesicular stomatitis virus.
Figure 1 Average serum interferon levels in mice cohortsExperiment 3Mice were injected with varying doses of Ph-LPS and monitored for 4 days. The lethal dose (LD₅₀) was defined as the minimum dose causing death in 50% of injected mice. Compared to He-N mice, results reflected a 10-fold increase in LD₅₀ for F1 mice and a 100-fold increase in LD₅₀ for He-J mice.
-According to the results of Experiment 3, which of the following could represent survival curves for F1 and He-J mice?

Question

Passage
Lipopolysaccharides (LPS) found in gram-negative bacterial cells can elicit a lethal degree of adjuvanticity, or immune activation, in LPS-responsive host organisms. In mice, responses may be modulated by abnormalities in the toll-like receptor (TLR) encoded by the Tlr4 gene closely linked to coat color on Chromosome 4. To investigate the effect of a particular Tlr4 mutation on LPS response, three experiments were performed following a cross between fully responsive He-N mice [tlr4(+) /tlr4(+) ] and He-J mice homozygous for the mutation [tlr4(d) /tlr4(d) ].Experiment 1Researchers isolated spleen cells for analysis of protein expression and LPS response. In cells isolated from F1 mice, both wild-type and mutant TLRs were distinguishable by protein electrophoresis. Following this first analysis, spleen cells from each cohort were exposed to 2 × 10⁵ SRC, an antigen formed by sheep erythrocytes. Cultures were then incubated in the presence or absence of Ph-LPS, with LPS extracted from Escherichia coli K345 cells using a phenol-water mixture. Titers of anti-SRC antibody were recorded on incubation day 5, with the results shown in Table 1.Table 1 Mean anti-SRC titers with standard error

Experiment 2Serum samples were assayed for interferon production 2 hours post LPS injection. Interferon was quantified using a plaque reduction assay on mouse cells challenged with vesicular stomatitis virus.

Figure 1 Average serum interferon levels in mice cohortsExperiment 3Mice were injected with varying doses of Ph-LPS and monitored for 4 days. The lethal dose (LD₅₀) was defined as the minimum dose causing death in 50% of injected mice. Compared to He-N mice, results reflected a 10-fold increase in LD₅₀ for F1 mice and a 100-fold increase in LD₅₀ for He-J mice.
-According to the results of Experiment 3, which of the following could represent survival curves for F1 and He-J mice?

Quizplus · Accepted Answer

11ecba2d_0f44_6db5_a3bf_13872f60bc81_MD0008_00 Survival curves plot the fraction or number of surviving members as a function of an independent variable, usually time after diagnosis (for humans) or drug dosage. In animal-based safety studies, survival curves are often used to assess lethal dose, which is the minimum dose causing death in 50% of group members. On survival curves, this data point can be observed as the dose (x-value) corresponding to 50% survival (y-value). In this case, survival is a function of LPS dose. Experiment 3 states that compared to the LD₅₀ for He-N mice, 10-fold and 100-fold increases in LD₅₀ were found for F1 and He-J mice, respectively. This result means that the LD₅₀ for He-J mice was 10 times greater than the LD₅₀ for F1 mice. The only survival curve that corresponds to this ratio is the one that shows that 50% of F1 mice died at a dose of 1 mg (LD₅₀ = 1 mg) and 50% of He-J mice died at a dose of 10 mg (LD₅₀ = 10 mg). (Choices A and B) These curves correspond to LD₅₀ values near 0.5 mg and 2.5 mg, or only a 5-fold difference. (Choice D) In this curve, the LD₅₀ for the F1 mice is 10 times greater than the LD₅₀ for the He-J mice. Educational objective: Survival curves plot percent survival against an independent variable, usually time or dosage. Survival curves can be used to determine LD₅₀, defined as the minimum dose causing death in 50% of test subjects.

Passage Lipopolysaccharides (LPS) Found in Gram-Negative Bacterial Cells Can Elicit a a Lethal