Natural Killer (NK) Cells

Immunology

See Also

• T lymphocyte
• Cell mediated immunity
• Cytokines

Definition

NK cells are a subset of T lymphocytes (white blood cells) which function as a first line of defense against cancer cells and viral infection. Their primary function is 'cytotoxicity', which basically can be thought of as the ability to cause spontaneous cell destruction of either a cancer or viral-infected cell.(1)

This cytotoxicity or overall activity level of NK cells (usually expressed as Lytic Units or LU) is far more important than the total quantity or overall number of cells.

However, NK cells do not kill indiscriminately. NK cells have several very specialized lectin-like receptors that recognize Major Histocompatibility Complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more HLA class I alleles leads to NK-mediated target cell lysis (2)

These receptors express several type II glycoproteins of the calcium-dependent lectin superfamily.

Discussion

In essence, specialized chains of carbohydrates are crucial to the functions of NK cells (just as they are for the expression of your blood type and the recognition of other-blood type substances found in nature).

Almost certainly, the number of diverse observations implies roles for carbohydrates in multiple areas of NK function, probably including target recognition, tissue distribution and post-binding events in the lytic cascade (3)

NK activity as a functional marker of health

Decreased NK activity is linked to a variety of diseases and according to the Center for Disease Control, low NK activity is present in most chronic illnesses. NK cell activity appears to be a reliable functional marker of health and for susceptibility to disease.

NK activity and malignancy

Changes in NK activity have been reported to be reliably associated with both the likelihood of metastasis and tumor response to therapy, matching in its reliability the tumor markers reflective of prostate cancer (PSA and TPS). (4)

Natural Killer cell activity in breast cancer

In breast cancer, a negative correlation is seen between NK cell activity levels and the maximum tumor diameter, meaning that the larger the tumor the more the patient had low NK cell activity. (5)

NK cell activity was also predictive of advanced disease (or spread of disease) in women with breast cancer. Destruction of cancer cells by NK cells is much lower in women with advanced disease (stages II, III, and IV) than in women with limited disease (stage I).(6)

Many of the new adjuvant approaches to cancer treatment that are currently being researched include the use of biological response modifiers (substances with the potential to modulate immune function). And, that at present, the most promising approach to immune modulation appears to be the utilization of biotherapeutic agents with the capability to positively impact natural killer (NK) cell cytotoxicity. (7)

NK activity and viral disease

Studies in humans consistently point towards a vital role of NK cells in the defence against chronic fatigue immunodeficiency syndrome (CFIDS), human immunodeficiency virus (HIV), herpesviruses, hepatitis B and C and other viral disorders. (8)

Chronic Fatigue Syndrome (CFIDS)

It is generally well-accepted that a viral component probably plays a role in the development of the symptomology. So, it is no surprise to find that CFIDS has been associated with low NK cell activity. In people with CFIDS, NK cell activity is also associated with the severity of CFIDS. (9)

Researchers have discovered that in an extended family with many members with CFIDS (5 of 6 siblings with CFIDS and 3 other immediate family members with CFIDS), NK cell activity was not only significantly lower in affected family members, but even non-CFIDS family members had NK cell activity levels lower than normal (falling between the very low level of the CFIDS individuals and normal values). (10)

In CFIDS, restoration of NK cell activity is associated with clinical recovery. (11)

Low NK cell activity has also been shown in HIV, chronic herpes simplex virus infection, and chronic viral hepatitis. (12,13,14)

Depletion of NK cells can drastically reduce survival time of animals infected with herpes simplex virus type 2 (HSV-2). (15)

An acute response against hepatitis B is actually associated with increased NK cell activity in the early phase of illness. However, in the recovery phase of illness NK cell activity moves back towards normal. Suggesting that NK cytotoxicity may be one mechanism that controls the HBV infection before other cytotoxic mechanisms become fully operative. (16)

In viral myocarditis, 80 % of cases had less than 14% of normal NK cell activity. However, after treatment for 3 months with Chinese herbs, average NK cell activity increased from 12.26 to 31.99 and at the same time clinical manifistations and EKG improved or returned to normal. (17)

References