a) Explain the mechanism of cytotoxicity employed by NK cells and cytotoxic T cells. (3 marks)
After a virus has infected a cell, and the proteins of that pathogen have been degraded, they are then presented via Class 1 MHC proteins on the infected cell's membrane for recognition by the immune system cells called cytotoxic t-cells.
These cytotoxic t-cells recognize the both the viral particle and the MHC protein. At this stage, they cytotoxic cell still isn't activated; it needs to be co-stimulated by near-by helper t-cells that produce interleukin-2. In turn, the cytotoxic t-cell releases cytotoxins and porforin that eventually cause the infected cell to undergo apoptosis (cell death). Mind you, there are millions of different types of cytotoxic t-cells; this diversity makes the body better equipped to recognizing antigens.
NK cells work in two ways,
indirectly and
directly.
Directly:- release perforins (creates pore in pathogen) and granzymes (induce apoptosis)
- interacts with cell without formal presentation
Indirectly:- Macrophage identifies Antigen with cytokines
- Cytokines stimulate NK to produce cytokines
b) Describe the differences between how NK cells and cytotoxic T cells recognise virally-infected cells. (4 marks)
Natural killer cells are not antigen-specific, while cytotoxic T cells are antigen-specific. In other words, cytotoxic T cells require Antigen-presenting cells (APCs), while NK cells do not require antigen-presenting cells (APCs). NK cells are part of the innate immune system, they always recognize the same, common patterns on microbial or cancer antigens.
(ii) A person is taking medication that it inhibits the transporter associated with antigen processing (TAP). If this person then became infected with influenza, describe how and why (by explaining the process involved) this drug would affect the response to viral infection. (6 marks)
TAP proteins are necessary for the loading of peptides onto class I molecules, a step that is essential for expression of class I MHC molecules on the cell surface. Lymphocytes in individuals with TAP deficiency due to a certain medication express levels of class I molecule significantly lower than normal controls.
Normally, the activity of NK cells is limited through the action of killer-cell-inhibitory receptors (KIRs), which deliver a negative signal to the NK cell following interaction with class I molecules. The deficiency of class I molecules in TAP-related individuals taking medication explains the excessive activity of the NK cells. Activation of NK cells further explains the absence of severe virus infections, which are limited by NK.
(iii) Compare and contrast the immune response of NK cells and cytotoxic T cells during primary infection and subsequent infections. Include a comment on the magnitude, kinetics and mechanism of activation observed.
At the end of the day, cytotoxic t-cells induce apoptosis; they do not directly kill the infected cell as natural killer cells do. NK activity is stimulated by IFN-alpha, IFN-beta, and IL-12, while cytotoxic t-cells (CTL) are stimulated by interleukin-2. NK cells are the first line of defense against virus infection, controlling viral replication during the time required for activation, proliferation, and differentiation of CTL-precursor cells into functional CTLs at about day 7.
NK cells differ from CTLs in several significant ways. First, NK cells do not express antigenspecific T-cell receptors or CD3. In addition, recognition of target cells by NK cells is not MHC restricted; that is, in many cases the same levels of NK-cell activity are observed with syngeneic and allogeneic tumor cells. Moreover, although prior priming enhances CTL activity, NK-cell activity does not increase after a second injection with the same tumor cells. In other words, the NK-cell response generates no immunologic memory.
Quick Reply
