Natural Killer Cells and Natural Killer T Cells

Natural Killer Cells (NK Cells)

  • It is a rather small cell population (5-15% of blood lymphocytes), containing a great number of azurophilic granules in the cytoplasm.
  • These large-size lymphocytes play a protective role of tremendous importance – ensure the lysis of cancer or virus-infected target cells regardless of their antigenic specificity (so-called non-immune cytolysis).
  • In addition, natural killers can destroy some bacteria and protozoans.
  • NK cells release a great variety of cytotoxic substances – perforin, which resembles in action the membrane attack complex (MAС) of the complementlymphotoxin (previously known as β-tumour necrosis factor), some special cytolytic enzymes, or granzymes that activate apoptosis.
  • Also, they induce cell death by direct contact activating apoptosis of target cells via CD95-Fas ligand interaction.
  • Membrane markers of NK cells are CD16 and CD56.
  • Infected cells become sensitive to natural killers owing to the impairment of HLA I-class expression on their surface. In normal conditions, NK cells bear inhibitory receptors (like CD158), which through interaction with HLA I-class antigens of the host cells permanently suppress NK activation.
  • After viral infection of the cell or its tumour transformation membrane, HLA I-Ag expression alters, and HLA antigen conformation appears to be distorted. This provokes natural killer activation with subsequent lysis of the infected cell.
  • In addition, NK cells were proven to have another type of surface molecules that directly initiate their killing activity – killer activation receptors.
  • Natural killers fill the breach in the full-value immune defence: while T-cytotoxic lymphocytes attack infected cells after the specific recognition of their antigenic peptides in complex with HLA I-class antigens, NK cells destroy the target cells, devoid of their own “self” markers.

NK cells as AntiCancer cells

  • Natural killer (NK) cells are emerging as an alternative to T cells in eliciting an immune response to tumours.
  • NK cells can kill multiple adjacent cells if they show surface markers which are associated with oncogenic transformation.
  • NK cells release preformed cytolytic granules, including perforin, and granzymes, of which function is to induce cell lysis.
Natural killer (NK) cell interacting with hepatoma cell (liver cancer).

Natural Killer T Cells (NKT cells)

  • Natural Killer T Cells (NKT) involves minor subpopulation of lymphoid cells that bears membrane markers characteristic for T cells and natural killer (NK) cells.
  • These are a heterogeneous group of T cells.
  • NKT cells are CD1d-restricted T cells that recognize lipid antigens.
  • NKT cells express both a T-cell receptor (TCR), characteristic of adaptive immunity and surface receptors for NK cells that express the innate immune response.
  • They express antigen-specific αβ T cell receptors together with CD56 marker on their membranes.
  • The main function of NK T  lymphocytes is to recognize and bind to lipid endogenous and exogenous antigens (e.g., lipoproteins of microbial cells).
  • These antigens are presented to NKT cells in complex with CD1 antigen. It has been found that the CD 1 molecule has a very similar structure with HLA I class antigens being capable of lipid binding.
  • Thus, NKT cells play a substantial role in the reactions of innate immunity promoting the elimination of microbial cells via the lipid components of their envelope (e.g., immunity against M. tuberculosis).
  • Invariant natural killer T (iNKT) cells also known as type I or classical NKT cells constitute the major population of T cells that express an invariant aβ T-cell receptor (TCR)

Immunoregulatory Function.

  • iNKT cells are divided into three subpopulations, ie.  CD4+, CD8+ or CD4- CD8- (DN).
  •  CD4+ iNKT cells tend to produce both Th1 and Th2-type cytokines having more immunoregulatory response compared to the other two.

Natural killer T cells