Immune system

In any case, I eventually recovered (and so did Jerry), but my immune system must have suffered serious damage, which manifested itself three years later, when I collapsed in my office one day and was found to be bleeding internally from a form of rare stomach cancer, which necessitated major surgery but was fortunately localized. I again recovered and have had no further difficulties since. Whether weakening and knocking out my immune system to overcome the previous problems had any effect is not clear, but it could have been a factor. Despite my health problems I was able to continue my work without much interruption, and the scientific productivity of my group has not... 

The viruses responsible for AIDS are human immunodeficiency virus 1 and 2 (HIV 1 and HIV 2) Both are retroviruses, meaning that their genetic material is RNA rather than DNA HI Vs require a host cell to reproduce and the hosts m humans are the T4 lymphocytes which are the cells primarily responsible for inducing the immune system to respond when provoked The HIV penetrates the cell wall of a T4 lymphocyte and deposits both its RNA and an enzyme called reverse transcriptase inside There the reverse transcriptase catalyzes the formation of a DNA strand that is complementary to the viral RNA The transcribed DNA then serves as the template from which the host lymphocyte produces copies of the virus which then leave the host to infect other T4 cells In the course of HIV reproduction the ability of the T4 lymphocyte to reproduce Itself IS compromised As the number of T4 cells decrease so does the body s ability to combat infections... 

Unfortunately, excess consumption of fatty foods has been correlated with serious human disease conditions. Effects on cardiovascular disease (95), cancer (96), and function of the immune system (97) have been shown. Numerous studies have been conducted to determine the effects of saturated, monounsaturated, and polyunsaturated fatty acids on semm cholesterol and more recently high density Hpoprotein (HDL) and low density Hpoprotein... 

Advances in immunology during the last part of the twentieth century have continued at a rapid rate and cytokines and immune cells having specific markers continue to be defined. A number of natural and synthetic immunotherapeutic agents have been discovered that can modulate components of the normal or aberrant immune system, through stimulation or suppression. However, most of these substances also have inherent adverse side effects. 

T-Lymphocytes (4,5) and other cellular components of the immune system also have equally wide implications in regulation of the normal immune system. The T-lymphocytes play a central role in the body s response to harmful antigens and tumor—host interaction (4). Responses involve antigens derived from vimses, bacteria, parasites, and tumors. T-ceUs also participate in the immune surveillance response, where self-antigens are recognized, but usually sequestered within the cell and, when exposed, become markers of cellular damage. 

Secondary immunodeficiencies (9) are much more common than primary ones and frequently occur as a result of immaturity of the immune system in premature infants, immunosuppressive therapy, or surgery and trauma. Illnesses, particularly when prolonged and serious, have been associated with secondary immunodeficiencies, some of which may be reversible. Acquked immune deficiency syndrome (AIDS) (10—12) may be considered a secondary immunodeficiency disease caused by the human immunodeficiency vimses HIV-1 or HIV-2. Hitherto unknown, the disease began to spread in the United States during the latter part of the 1970s. The agent responsible for this infection has been isolated and identified as a retrovims. 

The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

The toxicity of 2,4-pentanedione is shown in Tables 3 and 11 to be similar to mesityl oxide, and greater than most other 1,2- or 1,4-diketones or monoketones. Inhalation of low levels of 2,4-pentanedione can cause nausea, eye contact can induce stinging, and recurrent exposure to high concentrations (300—400 ppm) can adversely affect the central nervous system and immune system (325). 

G. Siskiud, "Agiug and the Immune System," iu H. R. Warner, ed.. Modem Biological Theories ofMging Raven Press, New York, 1987, pp. 235-242. 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

Human Immunodeficiency Virus. Human immunodeficiency vims (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which has no cure. HIV infects the cells of the human immune system, such as T-lymphocytes, monocytes, and macrophages. After a long period of latency and persistent infection, it results in the progressive decline of the immune system, and leads to full-blown AIDS, resulting in death. 

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

The prophylactic stimulation of the immune system using vaccines and bacterins is time-consuming. Of even greater value would be the abiUty to activate the system to combat a disease attack already underway, or to be able to increase the response to abnormal cells and neutralize neoplasia in any organ of the body. Several compounds, some unique entities and some already in use for other purposes, have shown potential utiUty as such nonspecific immune stimulants. 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

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