RELEVANCE OF AIET IN VIRAL INFECTION & CHRONIC FATIGUE SYNDROME
The antigen sensing of Viruses and cancer cells by the NK cells is by similar mechanisms. Evidences are piling up that The NK cells and CTLs which are the major weapons used in AIET against cancer are also effective against viruses and few other conditions as described below:
Human Immuno deficiency Virus (HIV):
Natural killer cells in addition to their non-specific antigen killing of tumour cells and viruses also work by another mechanism known as Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) in which the NK cells destroys the target cell that has been bound by specific antibodies. The antibodies bind through their variable antigen-binding sites to the viral antigen on the surface of the virus-infected cells and by crystallizable fragments (Fc) to CD16 on NK cells. This triggers the cytolytic functions of NK cells and results in killing of the virus-infected cells and secretion of cytokines and chemokines from NK cells (1).
Based on this mechanism it has been identified that HIV-infected cells bound by anti-gp120 antibodies are destroyed by NK cells (1). In another study it was demonstrated that freshly isolated NK cells preloaded with an HIV gp120-specific chimeric IgG1/IgA fusion protein efficiently lysed the HIV-infected target cells and NK cells pre-armed in this manner retained the capacity to kill targets over an extended period of time(2.. There are several studies which has proved the killing of HIV infected cells by NK cells (3, 4,5,6,7)
In view of the periodic upsurges of the global pandemics the swine(H1N1) and avian(H5N1) influenza , it has been shown that NKp46 , a receptor which is associated with cytotoxicity of NK cells can recognize the hemagglutinins of H1N1and H5 and that this recognition leads to virus killing both in vitro and in vivo (8)
Hepatitis C virus (HCV) plays a major role in development of chronic liver disease including cirrhosis and Hepatocellular carcinoma. The HCV uses complex and unique mechanisms to evade innate and adaptive immune responses and to establish persistent infection and chronic hepatitis. A study by Li et al (9) showed that NK cells are capable of secreting IFN-? to powerfully suppress HCV RNA expression further confirming the role of NK cells in the host innate immune defense against HCV infection.
Epstein Barr Virus(EBV):
EBV may be related to the development of malignancies such as Hodgkin’s disease and nasopharyngeal carcinomas. In a clinical study, 39 patients considered to be at high risk for EBV-induced lymphoma received 2 to 4 intravenous infusions of donor-derived EBV-specific T lymphocytes. Six patients who had greatly increased amounts of EBV-DNA on study entry indicating uncontrolled EBV replication showed 2 to 4 log decreases in viral DNA levels within 2 to 3 weeks after infusion and none developed lymphoma, confirming the antiviral activity of the donor-derived cells. Importantly there were no toxic side effects after the therapy (10). In another study a 2-year-old girl with Hurler's syndrome who developed multiple central nervous system (CNS) EBV LPD lesions 1 year after unrelated donor hematopoietic stem cell transplantation was given low-dose oral hydroxyurea. The patient improved clinically, with a decrease in size of multiple EBV LPD brain lesions. Subsequently EBV-specific cytotoxic T-cell lymphocytes were administered and the patient continued to do well (11)
Chronic Fatigue Syndrome(CFS):
Chronic Fatigue syndrome is a complex disorder with non-specific and varied etiologies including genetic predisposition, infection by viruses and pathogenic bacteria, hypothalamic-pituitary-adrenal axis abnormalities, immune dysfunction as well as psychological and psychosocial factors. It has been known for years that the most consistent immunological abnormality detected among these patients, when compared with normal controls is low natural killer (NK) cell cytotoxicity (12) and there is positive correlation between low levels of NK cell activity and severity of the disease (13).
Further, there is a predominance of a Th2-type response which favors the function of B lymphocytes or the humoral arm of immunity over Th1 response which favors the function of macrophages and natural killer cells. Predominance of a Th2-type response has been found to be consistent with pathologies, such as autoimmunity and atopy (14) which is unfavourable. Hence immunotherapeutic approaches that help in either induction of Th1 predominance or strike a balance between Th1 and Th2 response or enhance NK cell activity by either injection of T lymphocytes, using food supplements that enhance natural killer activity, immunoglobulin therapy and injection of Dialysable leucocyte extract have been tried by various groups with varied success (15, 16,17).
In addition to the above mentioned conditions, Imai et al (18) have found after an 11 year follow-up of 3625 volunteers that the NK cell profile of cancer victims is significantly lower than their peers without cancer. This finding could be the basis for a study of long term effects of intermittent AIET in people with cancer history in their family and also with people who undergo stress related decrease of NK cell profile.
Thus individuals with lower immunity, those susceptible to cancer and viral infections, those under stress, those with diagnosis of chronic fatigue syndrome and those suffering from above mentioned viral infections can undergo Autologous immune Enhancement therapy (AIET) in addition to the other therapies they are undergoing such as antiviral therapies and supplementary therapies to enhance their immunity for effective response against the diseases.
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