2B Briefly describe the concept of \"missing self\" as it is related to NK cell

Question

2B Briefly describe the concept of "missing self" as it is related to NK cell activation. What receptors are involved? What are the role of ITIMs and ITAMs in NK cell activation? (3 points) 2C Compare and contrast how NK cells and CD8 T cells recognize and kill virally infected cells. In your answer, discuss the role of MHC, how the NK and CD8 T cells are specifically activated, and the mechanisms used to kill their targets. Clearly labeled diagrams with text that explains the diagram are acceptable. (3 points)

Explanation / Answer

Solution to Question 2B

The answer to the question briefly describe the concept of "missing self" is as follows:

NK cells belong to the class of innate immune system. They act as anticancer and antiviral agents by killing the tumorigenic and virus-infected cells. Generally, when a cell is infected by a virus, the affected cell express higher levels of MHC class I molecules. T-cells specifically recognize these molecules expressed by the infected cells and destroy them. In order to avoid the T-cell mediated immune response, some pathogens downregulate the expression of MHC class I molecules. Interestingly, NK cells evolved to tackle this challenge and they are capable of identifying infected cells which express low levels of MHC class I molecules. The ability of NK cells to identify the infected cells which express low levels of MHC class I molecules is termed as "missing self".

The answer to the question What receptors are involved?

Receptors such as activating receptors and inhibitory receptors present on the surface of NK cells play a pivotal role in identifying the self (healthy) from altered self (infected/ tumorigenic cells). These are involved in the activation of NK cells.

The answer to the question What are the role of ITIMs and ITAMs in NK cell activation?

Immunoreceptor tyrosine-based inhibition motifs (ITIMs) are found in the cytoplasmic tail of inhibitory receptors. They play a major role in negative signaling pathways of NK cell activation. They specifically bind to Immunoreceptor tyrosine-based activating motifs (ITAMs) and block their activity. They are also involved in the phosphorylation and dephosphorylation of intracellular components.

Immunoreceptor tyrosine-based activating motifs are associated with activation receptors and they are involved in the activation of NK cells. They trigger the signaling pathway which activates the transcription of cytokine and chemokine genes.

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