THE ROLE OF NK CELLS AND THE IMPORTANCE OF IMMUNOTHERAPY IN THE TREATMENT OF PATIENTS WITH CANCER:

The natural killer cells (NK cells) are our body's natural defense against cancer cells. They circulate through our body, seeking cells that have unusual molecules on their surface which indicate that the cell is either a tumor cell or it is infected with a virus.

When such a cell is found,  the NK cell opens up and extends a tentacle to the ailing cell and engages the "Killer Activating Receptor" in preparation to destroy the cell. Another tentacle reaches out to seek another spot in the cell, the "Killer Inhibitory Receptor". If this spot is not found, the NK cell blasts the sick cell with particles that punch holes in the bad cell wall and pumps venom into it that surges in and out of the cell until it breaks out.

This event is enacted 10,000 times a day in a healthy person's body as tumor cells are routinely destroyed when they are formed. Below shows a picture of a Natural Killer cell in its normal state as it patrols the body. 

Natural Natural killer cells (NK cells) are the most aggressive fighters of all cells in the immune system. They are the first line of defense against mutant and virus infected cells like Severe Acute Respiratory Syndrome (SARS) or West Nile that threaten one's health. They are lymphocytes with no immunological memory and are part of your innate immune system. NK cells make up about 5 to 16 percent of the total lymphocyte population. Their main function is to destroy infected and cancerous cells.

NK cells do not kill indiscriminately. They look for a banner flown by normal cells. If the NK cell sees this banner, it receives a signal to spare that cell. This signal overrides the NK cell's urge to kill. If this banner is absent on the target cell the NK cell proceeds with its attack. It attaches to the target and releases a lethal burst of chemicals that penetrate the cell wall. Fluids begin to leak in and out and eventually the cell breaks out.

Besides their role in controlling of infections, NK cells help in the regulation of other aspects of the immune system which effects our general health.  Today modern science has identified the players and the mechanism by which the immune system works. However, Traditional Chinese Medicine has thousands of years of continued practice, and through accumulated experience of trials and errors,  Chinese herbalists have successfully identified, processed, and used herbs, and herb derivatives in the treatment of diseases. Traditional Chinese pharmacology stands alone like no other medical system in producing strong, effective, and harmless herbal formulas to boost the immune system.       

The clinical effectiveness of immunotherapy with Immuno SG;has been well documented. The active ingredients in this natural herbal formula called Immuno SG;have been scientifically studied and demonstrate to highly elevate the body's production and activity of NK cells, T cells, B cells, interferon, and interleukin. For maximum potency, Immuno SG; is prepared with full spectrum concentrated extract powder at  the concentration ratio of 5:1. The required drying agents are also powder from the original herbs, with no preservatives and no  artificial ingredients. This natural herbal formula can effectively support the immune systems of cancer patients, patients undergoing chemotherapy or radiation, and patients that have already received those therapies.  Besides helping cancer patients, Immuno SG; can also benefit patients with viral hepatitis, and other immune deficiency conditions.  Immunotherapy to help increase NK cell efficacy is becoming available and will become more widely used as knowledge of the immune system expands. 

Observe the heavy section of the cell wall at the top of the first picture, which contains the tentacles and venom sacs and how they are now deployed outside the cell wall on the right side of the cell in the second picture.

NK Cell Destroying a Tumor Cell:

You can see the two tentacles, the one with the venom sacs and the "Killer Activating Receptor" and the other that didn't find the site to inform the NK cell to stop the killing operation with the ."Killer Inhibitory receptor" and the MHC-1 cells.

Exposition of the killing action and mechanism of NK cells:

The Fab portion of the antibody binds to epitopes on the "foreign" cell. The NK cell then binds to the Fc portion of the antibody. The NK cell is then able to contact the cell and release pore-forming proteins called perforins, proteolytic enzymes called granzymes, and chemokines. Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation. As a result, the cell breaks into fragments that are subsequently removed by phagocytes. Perforins can also sometimes result in cell lysis.

Cell Apoptosis Induced by NK Cells:

The NK cell releases pore-forming proteins called perforins, proteolytic enzymes called granzymes, and chemokines. Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation. As a result, the cell breaks into fragments that are subsequently removed by phagocytes. Perforins can also sometimes result in cell lysis.

Following is a scientific report by Jerry T. Thornthwaite, Ph.D. describing his discovery of the NK cells in 1972.

Advances in Cancer Detection
"My Discovery of the Natural Killer Cell",  by Jerry T. Thornthwaite, Ph.D.

In 1972, I presented a poster session with my major Professor, Dr. Bob Leif, at the annual Reticuloendothelial Society Meeting. On my poster, I presented on very unusual cells from the spleen (and later from the lymph nodes) of non-immunized mice that destroyed sheep red blood cells (SRBC) on contact. I came very close to publishing the article in Science which took some time and effort, but the conclusion was that it was more suitable for the immunology journals. The papers were accepted in the Journal of Immunology. I did not know the proper name for these cells but was able to develop a way of enumerating them, determine their density and enrichment in linear bovine serum albumin gradients and study their morphology utilizing light, scanning electron and transmission electron microscopy. Many years later, I developed a clinical application by in vitro enriching natural killer cells for infusion into patients.

Currently, I am investigating natural substances that are supposed to increase the natural killer cell response. Unlike complement mediated IgM antibody destruction of SRBC, which showed lyses of "plaques" of SRBC appearing as deflated balloons (Fig. 1), the complete destruction of the SRBC did not require prior immunization with SRBC or complement (Fig. 2). Thus, I gave them the name "complement independent plaque-forming cells" (CIPFC) or "rough lymphocyte plaque-forming cells" when I was able to perform scanning electron microscopy (SEM). Later, Heberman (1973) and Oldham (1973) used the term "Natural Killer Cell".

      
 

Figures 1 and 2. Two IgM antibody-complement plaques showing the deflated SRBC in the plaque area (left) and the "rough surfaced" "complement independent-nonimmunized" plaques (right).

In 1973, I developed a technique using alcian blue to stain cells that were dead prior to glutaraldehyde fixation. Viable cells, prior to glutaraldehyde fixation, did not stain. I used this technique to locate the CIPFC destroying target tumor cells. The killed tumor cells were also easy to see at the later stages by the blebbing of the membranes of the tumor cells (Fig. 3 and 4).

     

Figures 3 and 4 showing Nomarski optics of the binding of complement independent cells (left) and cytoplasmic "blebbing" of the target mouse P815 plasmocytoma cells from lymph nodes of non-immunized mice.

Working with Marilyn Cayer, we were able to section en face the alcian blue areas and perform electron microscopy.

Figure 5. CIPFC (Natural Killer Cell) destroying a target tumor cell.

Natural Killer Lymphocytes:
Natural killer (NK) cells are antigen nonspecific lymphocytes which recognize foreign cells of many different antigenic types. These cells are an important first line of defense against newly malignant cells and cells infected with viruses, bacteria, and protozoa (Natural Killer Cells). About 5 to 16 percent of the total lymphocyte population contains natural killer cells. NK cells have the ability to attack foreign cells without first having to recognize specific antigens; a characteristic lacking in CD4+ lymphocytes (Stine, 1997). Similarities in development, morphology, lytic mechanism and cell-surface phenotype indicate that NK cells and cytotoxic T cells are closely related lineages. The effector functions of both types of cells are controlled by MHC class I glycoproteins, and both express receptors that bind these glycoprotein molecules. The main difference between the two cells is that cytotoxic T-cells recognize infected cells by the peptides their MHC class I molecule present, while NK cells look for the absence of MHC class I molecules. It has been proposed that NK cells complement cytotoxic T-cells by taking charge in situations where MHC class I expression is hindered through the effects of virus infection (Nature, 1995).

NK cells have evolved a mechanism for mediating host defense against infection with viruses by having the ability to distinguish infected from uninfected cells. Although the exact mechanism is not clear at the present time, one possible mechanism may be that NK cells selectively kill target cells bearing low levels of MHC class I molecules on their surface. Natural killer cells have two types of surface receptor which aid in distinguishing infected from uninfected cells. The first receptor, NKR-P1, recognizes a wide variety of carbohydrate ligands found on many cells. The activation of NK cells to kill normal cells displaying these ligands is prevented by a second receptor, a C-type lectin, which binds to MHC class I molecules and inhibits NK activity (Janeway-Travers, 1996). NK cells kill target cells by releasing perforin which damages the target cell membrane and results in death of the cell. Inducing apoptosis in the target cell is another mechanism NK cells utilize to kill infected cells (Natural Killer Cells). If the specific functions of NK cells malfunction or are killed themselves, an important component of the immune attack is destroyed.

Most of the studies related to the immune system and HIV concentrate on T lymphocytes, B lymphocytes, and antigen-presenting cells. However, studies reported so far have found that NK cells can be lethally infected by HIV, and NK cell cytotoxic functions are impaired during the course of infection (Dissection). In 1989, a researcher by the name of Paolo Lusso discovered that infection with herpesvirus-6 can cause a decline in the body's natural killer cell response. This was the first time researchers have shown that natural killer cells were vulnerable to any kind of viral attack. It was also the first real evidence that infection with this herpesvirus might play a role in AIDS. In the same year, Lusso's team also showed that herpesvirus-6 attacks CD4+lymphocytes (Science News, 1993). As mentioned earlier, CD4+lymphocytes are the primary targets of HIV.

Although natural killer cells do not normally produce the CD4 molecule and are typically resistant to HIV's attack, herpes-infected natural killer cells were found to manufacture the CD4 receptor molecule that provides an entrance for HIV. Experiments have shown that when HIV was added to cultures of herpes-infected natural killer cells, HIV was able to infect those cells (Science News, 1993). So although NK cells cannot be infected by HIV as a normal functioning cell, once it is infected with herpesvirus-6 it manufactures the CD4 receptor which makes it a primary target of HIV. The consequence of NK cells becoming infected with HIV results in an increase in malfunctioning NK cells along with a decline in the natural killer cell response; rapidly leading to the development of AIDS.

These cells are sometimes called large granular lymphocytes (LGL's). NK cells have some surface markers in common with T cells, and they are also functionally similar to cytotoxic T lymphocytes (CTL's). Like CTL's, NK cells are particularly important in the killing of cellular targets (usually tumor cells). Unlike CTL's, however, the killing by NK cells is nonspecific, they do not need to recognize antigen/MHC on the target cell. NK cells do not have a T cell receptor and are not T cells.

An NK cell kills a target cell by releasing perforin (and other molecules) which damages the target cell membrane leading to death. NK cells also cause death by inducing apoptosis in the target. The cytokine TNF alpha is released by the NK cells and may be involved in this process.

Natural killer (NK) cells are well known for their ability to kill certain tumors. However, it is now recognized that NK cells have a significant role in host defense against invading pathogens, particularly intracellular organisms, and are capable of in fluencing the specific, acquired immune response. The ultimate goal of our work is to elucidate the function of NK cells in normal and abnormal immune responses and to derive targeted therapeutic interventions that influence these innate effector cells.

Immune System & NK Cells
 
"Research has shown that low Natural Killer cell activity is present in nearly all illness." Dr. Jesse Stoff

In The Ultimate Nutrient, Dr. Stoff states the following:

"In recent years the immunological community has begun to recognize and study special cells that are a part of our immune system called Natural Killer (NK) cells. These cells contain a large array of armaments...

In my studies I have become aware of the severe deficiency that exists in our NK cell reserves. Studies indicate that at one time we carried high levels of NK cell activity. Current measurements indicate we are about 10-20% of those levels today. The implications of this fact are staggering."

Dr. Stoff isn't the only researcher to pay attention to NK cells and the immune system. Scientific reaerch on this subject have also taken place in China, Japan, South Korea, and other countries. And, in the United States, there are many others, among them is the Pittsburgh Cancer Institute, Department of Pathology.

This is mainstream medical research. In 1994, the Pittsburgh Cancer Institute produced an 11 page study on NK cells. They demonstrated a correlation between low NK cell activity and cancer, viral and bacterial diseases and autoimmune diseases. They state the following: 

• The correlation between low NK cell activity and serious viral infection has been well documented.
• In general, patients with low NK cell activity appear to be at higher risk for infections.
• Patients with autoimmune diseases may have abnormalities in NK cell activity...
• Impaired NK cell function has been reported in patients with connective tissue diseases including lupus and rheumatoid arthritis.
• In cancer, NK cells are thought to be the first line of host defense against blood-borne metastases.
• It is clear that chronically low levels of NK cell number or activity in patients with cancer or other diseases may be associated with more severe symptoms or increased risk of disease progression."

What do NK cells do that make them so important?
NK cells are one of many interactive components of the immune system, however, they have some very special qualities. NK cells are in the T cell family and know "self" from "non-self" like other T cells. NK cells focus on killing virally infected cells and cancer, but will kill bacteria, parasites and fungi. What's really special about them is that they have a completely different way of recognizing invaders. They specialize in killing virus and cancer cells that other parts of the immune system no longer "see" for whatever reason. Any cell that is "hiding" is vulnerable to attack by NK cells if they are capable enough to respond. This is routine for them as cancer and virus cells have a tendency to to "hide". However, when other parts of the immune system becomes overwhelmed so as to slow or stop their function, NK cells are the last line of defense a person has.

Decreased NK cell activity means that either the person is sick or will be. On the other hand, chronic or severe illness could indicate low NK cell activity among other compromised immune system factors. Measurement of natural killer cells activity is a very useful evaluation of the immune function status.

Immuno SG; is a powerful herbal medicine specifically formulated to boost the body's production of NK cells and NK cells activity. TCM Pharmacy; 

   Back                       Home Page