NK cell
NK cells are lymphocytes in the same way as T and B cells, with which they also share the same common lymphoid progenitor. However, they are described as cells of innate immunity, even if some of their characteristics are on the border between innate and adaptive immunity. They participate in cellular immunity.
They are said to be on the border between innate and adaptive immunity because they have characteristics of both families of immunity:
- Characteristics of innate Immunity
No somatic recombination of receptors
No antigen specificity - Characteristics of adaptive immunity
Like T and B cells, NK cells undergo an education process which allows them to distinguish healthy cells from the abnormal cells which will be their targets.
Haematopoiesis / cytology
They share the common lymphoid progenitor with T and B cells from which they are morphologically inseparable (small cells with a round nucleus with a high nuclear-cytoplasmic ratio at rest). They are rarely found in circulating blood where they represent 10% of lymphocytes.
Functions
Cytotoxicity
The NK cell recognises cells to kill in two ways:
- ADCC (Antibody Dependent Cell Cytotoxicity)
NK cells will be able to target and kill cells to which immunoglobulins are attached thanks to the expression of receptors fixing the Fc fragments of immunoglobulins (CD16).
- The missing-self theory
NK cells will exert cytotoxic activity restricted to cells that have decreased expression of Class I HLA class molecules on their surface (for example, infected cells), or HLA molecules different from those present during their formation (for example, foreign cells during a transplant). It is the KIRs (Killer Immunoglobulin-like Receptors) expressed on the surface of the NK cell that are responsible for this recognition of abnormal cells, because they are sensitive to the presence or absence of classical or non-classical Class I HLA molecules.
There is a great diversity of expression of KIR receptors on the surface of NK cells, a consequence of the genetic polymorphism of this region of the genome. KIRs can in particular carry an activating or inhibitory function and the combination of activating KIRs and inhibitory KIRs versus the combination of Class I HLA molecules leads to a balance specific to each individual. In the physiological state, the normal cells of the individual are protected from cytotoxicity, while the cells whose expression of Class I HLA molecules has been modified will be lysed by the NK cell (see NK cell activation).
This mechanism of recognition of NK cells via missing-self makes it possible to eliminate abnormal cells which would try to escape the cytotoxicity of CD8+ T cells by underexpressing their Class I HLA molecules!
Once the cell to be lysed is recognised, the cytotoxic mechanisms used by the NK cell are very similar to those of the CD8+ T cell:
- the perforin/granzymes pathway: the NK cell degranulates, on the one hand, the perforin, which forms pores in the membrane of the targeted cell, and on the other hand, the granzymes which lead to their lysis.
- “cell death receptors”: they cause apoptosis of the targeted cell: FAS (on the targeted cell) / FAS ligand (on the NK cell), TRAIL (on the NK cell) / TRAIL ligand (on the targeted cell)
Cytokine secretion
Particularly pro-inflammatory, they will increase the recruitment and activation of dendritic cells and macrophages.
What needs to be remembered
NK cells are cells at the border between innate and adaptive immunity. They mainly exert a cytotoxic function directed against:
- cells already targeted by antibodies (e.g., anti-HLA antibodies on donor cells in transplantation)
- cells with reduced expression of their Class I HLA molecules (e.g., infected or tumour cells)
- cells with Class I HLA molecules different from those encountered during NK cell education (e.g., donor cells in transplantation)
