Natural killer Cells, Viruses and Cancer

Human Natural killer Cells

Introduction to Natural Killer cells:

Natural Killer cells was discovered in the year 1970. It is a type cytotoxic lymphocyte that represents major part of innate immune system and is specialized to kill certain types of target cells, especially those that became infected with virus or have become cancerous. NK cells are produced in response to infections by healthy bodies. They are self-activated and play an important role in elimination of tumors and virus-affected cells. These NK cells release proteins called perforins and granzyme, a cytoplasmic granule, which destroys the target cell by apoptosis.

Natural Killer Cells are also defined as large granular lymphocytes (LGL) and comprise the third kind of cells other than B and T Lymphocytes. They usually express surface marker CD16, CD56, and CD8 (only 80% of NK cell) in human.

They are termed as natural killers cells because of the fact that they do not require activation to kill cells with missing “Self” markers of MHC class l.

Importance of Natural killers cells:

Natural killer cells are derived from Pluripotent Hematopoietic stem cells and are considered as important cells of the immune system. They perform two main functions:

  1. Cytolytic activity
  2. Cytokine producing capacity

These two functions are mainly managed or regulated by numerous activating and inhibitory receptor, including newly discovered receptors that selectively triggers the cytolytic activity in a MHC independent manner. Based on these two activities, NK cells are thought to play a critical role in immune surveillance and cancer therapy. New discoveries and research proposed that NK cells play a major role in control of infections, particularly in Plasmodium falciparum infection and in fetal implantation.

Mechanism of action:

Natural Killer Cells are cytotoxic and contain small granules in their cytoplasm, which in turns contain special proteins such as perforin and proteases known as granzymes. When these proteins and Proteases are released close to a cell intended for killing, perforin create pores in the cell membrane of the target cell through which granzymes and associated molecules can enter, inducing apoptosis. Natural Killers cells are activated in response interferons or macrophages derived cytokines. Patients with deficient NK cells are highly susceptible to early phase of herpes virus infection.

In order to protect the body from virus and other pathogen, NK cells require mechanism that could determine weather a cell is infected or not. The mechanism is still under research; “altered self” is thought to be involved.

Natural Killer Cell includes two types of surface receptors (activating receptor and inhibitory receptor) to control their cytotoxic activity. These receptors recognize MHC class l alleles that could explain the killing process of NK cells for low level of MHC class l molecule.

Types of Receptors:

There are four types of receptors and are differentiated by structure:

  • CD94 NKG2 (Heterodimers)
  • LY49 (Homodimers)
  • KIR (Killer-cell immunoglobulin-like receptors)
  • ILT or LIR (Leukocyte inhibitory receptors)

According to christine Biron it is important understand how to keep NK cells around, because they can be lost. Her work reveals two important aspects of NK cell biology. The first is to understand how to keep NK cells instead of loosing them, and second is to keep them around, as they have an important regulatory function to limit adaptive immune response. Absence of NK cells leads to unregulated adaptive immune system and in some cases it may leads to death.

Conclusion:

Understanding the mechanisms of NK cell functions may lead to fresh therapeutic strategies for the treatment of human disease, in general, and particularly in the fight against malaria. However, much research remains to be done.

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