Question

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

Answer 1

Natural Killer (NK) Cells are lymphocytes in the same family as T and B cells, and they are best known for killing virally infected cells, and detecting and controlling early signs of cancer. NK cells are also found in the placenta and may play an important role in pregnancy. NK cells have the ability to kill tumour cells without any priming or prior activation (in contrast to cytotoxic T cells, which need priming by antigen presenting cells). They are named for this ‘natural’ killing.

The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis.

  

Cytokines play a crucial role in NK cell activation. As these are stress molecules released by cells upon viral infection, they serve to signal to the NK cell the presence of viral pathogens in the affected area. NK cells are activated in response to interferons or macrophage-derived cytokines.  

• For NK cells to defend the body against viruses and other pathogens, they require mechanisms that enable the determination of whether a cell is infected or not. The exact mechanisms remain the subject of current investigation, but recognition of an "altered self" state is thought to be involved.
• To control their cytotoxic activity, NK cells possess two types of surface receptors: activating receptors and inhibitory receptors, including killer-cell immunoglobulin-like receptors. Most of these receptors are not unique to NK cells and can be present in some T cell subsets, as well.

The inhibitory receptors recognize MHC class I alleles, which could explain why NK cells preferentially kill cells that possess low levels of MHC class I molecules. This mode of NK cell target interaction is known as "missing-self recognition", MHC class I molecules are the main mechanism by which cells display viral or tumor antigens to cytotoxic T cells.

• A common evolutionary adaptation to this is seen in both intracellular microbes and tumors: the chronic down-regulation of MHC I molecules, which makes affected cells invisible to T cells, allowing them to evade T cell-mediated immunity. NK cells apparently evolved as an evolutionary response to this adaptation .

Schematic diagram indicating the complementary activities of cytotoxic T cells and NK cells

Natural killer cells often lack antigen-specific cell surface receptors, so are part of innate immunity, i.e. able to react immediately with no prior exposure to the pathogen. In both mice and humans, NKs can be seen to play a role in tumor immunosurveillance by directly inducing the death of tumor cells , even in the absence of surface adhesion molecules and antigenic peptides. This role of NK cells is critical to immune success particularly because T cells are unable to recognize pathogens in the absence of surface antigens. Tumor cell detection results in activation of NK cells and consequent cytokine production and release.

NK cells influence adaptive immune responses through a variety of mechanisms. NK cells can affect T cells directly by releasing or consuming cytokines or by killing T cells. NK cells can influence T cells through indirect mechanisms such as by regulating APC activity.