Types of Gram-negative bacteria

Question 1: Based on the figure presented above, what is the most likely ligand for TLR-XX? Be as specific as possible, and justify your answer based on these data.

Question 2: Based on these data, where would you MOST likely find toll-like receptor-XX (TLR-XX) among the following options? Justify WHY you selected the option that you chose for full credit. Your justification must be based on the data that are presented here, not the type of bacteria.

A. On the cell surface

B. In the endosome/ lysosome

C. In the nucleus

D. In the mitochondria

E. In the endoplasmic reticulum

Question 3: Would you predict that TLR-XX is able to recognize other types of Gram-negative bacteria, in addition to the one that was used in this experiment? Explain WHY or WHY NOT?

NK cells and Red Blood Cell tolerance: Red blood cells (RBCs) lack a nucleus and do not express MHC class I proteins. Although RBCs express CD47, a cell-surface protein that is associated with protection from cell-killing, its expression alone does not explain why NK cells do not kill RBCs1.

Pulak Ranjan Nath, Dipasmita Pal-Nath, Ajeet Mandal, Margaret C. Cam, Anthony L. Schwartz, David D. Roberts; Natural Killer Cell Recruitment and Activation Are Regulated by CD47 Expression in the Tumor Microenvironment. Cancer Immunol Res 1 September 2019; 7 (9): 1547–1561. https://doi.org/10.1158/2326-6066.CIR-18-0367 (Note this reference if provided for your information – You do not need to read this paper to answer the question 4)
Question 4: Based on your understanding of how NK cells distinguish between target cells for cell-killing and healthy cells that are not killed, explain why RBCs are not killed by NK cells. Using complete sentences support your answer with evidence from the suggested videos and/or readings. Include references citation in text format is APA, 400-600 words

Sample Solution

RBCs are not killed by NK cells due to the lack of MHC class I proteins on their cell surface. While RBCs do express the CD47 protein, which is associated with protection from cell-killing, other factors are also necessary for a complete picture of why they don’t get destroyed by these cytotoxic lymphocytes in the body. The absence of MHC class I proteins makes it very difficult for NK cells to recognize RBCs as targets for attack or destruction, and instead will focus their attention on other cells that may actually be dangerous to the body (1)

NK cells use a combination of activating and inhibitory receptors on their surfaces to determine whether or not they should destroy target cells. They can only kill if the activating signals overwhelm any inhibitory signals present (2). For example, some activating receptors recognize MHC molecules while inhibitory receptors detect missing self markers such as CD200 and CD155 that are found on healthy host tissues but absent from foreign invaders (3). Since RBCs lack MHC molecules entirely, there would be no signal detected by an NK cell’s activating receptors that could possibly overcome any potential inhibitory signals sent out by its own cell surface markers. Therefore, NK cells do not see them as targets for destruction and thus ignore them completely (4).

In summary, RBCs are spared from being attacked by NK cells due to their lack of MHC class I expression combined with an inability for NK cells’ activating signals to override its own inhibitory ones when recognizing these red blood cells. This allows them to remain safe within our bodies without facing unwarranted destruction at the hands of our immune system’s natural killer lymphocytes.

References:
1. Nath PR et al., 2019; 2. Janeway CA et al., 2001; 3. Lanier L et al., 1998; 4. Lanier LL & Cwirla S., 1990

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