Natural Killer 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 complement, lymphotoxin (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 that 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 Cells
Natural killer (NK) cell interacting with hepatoma cell (liver cancer).

Natural Killer T Cells (NKT cells)

  • Natural Killer T Cells (NKT) involves a 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 responses compared to the other two.

Natural killer T cells