Alex Wong's List: Henry

• The Use of Transfer Factor in Immunorehabilitation Therapy of HIV Infection

    

  Excerpted from "Transfer factors Use in Immunorehabilitation After Infectious-Inflammatory and Somatic Disease - Methodological Letter" by the Ministry of Health and Social Development of the Russian Federation, Moscow, 2004.

    

  Acquired Immunodeficiency Syndrome (AIDS) is one of the most serious problems confronting modern medicine. For HIV patients immune modulation therapy (i.e. the restoration of normal immune function) is aimed altered immune mechanisms and at the pathogenic agent(s). 

   

  The results of studies conducted (10,11) showed that TF PLUS treatment significantly improved the immune status of HIV patients. The product also proved useful in other aspects of therapy as for example the level of circulating immune complexes (CIC) decreased to normal values in 50% of patients receiving TF PLUS.

   

  Because the CD4 T-helper marker is a HIV receptor, whereas HIV is tropic to Tlymphocytes and other immunocompetent cells it infects mainly T-helpers while sparing cytotoxic cells. A significant increase in T-helper, (CD4+) levels in patients receiving TF PLUS is an important aspect in helping to attain the main goal of such patient treatment, namely, maximum life extension and preservation of its quality.

   

  In HIV therapy patients received TF PLUS, 1 capsule 3 times daily for two weeks. Repeated courses of TF PLUS are prescribed during the process of out-patient follow-up as based upon the investigative results of a patient's immune status.

• Nutritional Healing
   Blake Graham, BSc (Honours), AACNEM
  Clinical Nutritionist
   Suite 5, 531 Hay Street, Subiaco, Western Australia, 6008
   Phone: (08) 6380 1320
   Email: See Contact page
   *Non-Perth residents may enquire about phone consultations.

• Autoimmune diseases are caused by your own  immune system   starting to react and attack your own body.    It is recommended that  Transfer Factor   Tri-Factor   be used in autoimmune conditions.<!--google_ad_section_end -->   Transfer Factor Plus   is generally preferred for conditions caused by   infection. Transfer factors    suppress over active immune system to ease   autoimmune conditions.

• Drug companies are   eager to expand this approach into therapies for   other autoimmune diseases, which have   been on the increase since the 1950s, but have   few good treatments available today. Translating   principle into practice will not be easy,   however. The   immune system is a vast network with a   bewildering array of warrior - from antibody -   making B cells to various kinds of T cells that   can enhance antibody production, kill   virus-infected cells, initiate inflammation and   finally shut down and immune attack. B cells and   T cells also make more than 100 types of helpers   called cytokines that assist in orchestrating   every aspect of the immune assault.

    Maini and Feldmann   zeroed in on one such cytokine called tumore   necrosis factor (TNF). It derives its name fro   its ability to kill cancer cells, but in excess   it also initiates the inflammation of    rheumatoid arthritis. In a small clinical   trial, they tested and anti-TNF antibody in 20   patients who had failed to respond to other   treatments. Within hours, the recipients started   feeling better. In six weeks, they were climbing   stairs and even golfing. Today there are three   TNF blockers on the market for    rheumatoid arthritis - Remicade (which Maini   and Feldmann used), Enbrel and Humira.

    But not all patients   with   rheumatoid arthritis respond to these costly   TNF blockers - nor does anti-TNF therapy hold   the master key to all autoimmune diseases.   "There may be some therapies that are broadly   applicable across a wide range of disorders, and   other that are particular to one disease," says   Bluestone. So doctors are targeting other   immune-system components, like B cells and T   cells, in an attempto to tame various autoimmune   problems. Genentech's drug Rituxan, a   bioengineered antibody against B cells, is now   in early trials for   lupus, the most challenging   of all autoimmune diseases because it   affects not just ne type of tissue, but organs   throughout the body.
• Unfortunately, even   if it works perfectly, the antibody is not a   cure. By the time  type 1   diabetes is diagnosed, the pancreas has lost   80 to 90 percent of its insulin-making ability.   That's why the ideal time to treat autoimmune   disease is early on, before irreversible   damage has been done. Beginning next year, the   Dinora Trial will test Remicade in patients who   have had symptoms of    rheumatoid arthritis for no longer than 12   weeks. The goal is long-term remission. Other   doctors are trying to uncover ways of testing   for autoimmune diseases before symptoms   even emerge. They have their work cut out for   them.

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• Successful control of viruses by NK cells--a balance of opposing forces?

   

  <!--AuthorList-->Scalzo AA.

   

  Dept of Microbiology, School of Biomedical and Chemical Sciences, Queen Elizabeth II Medical Centre, The University of Western Australia, Nedlands, WA, Australia. scals@cyllene.uwa.edu.au

   

  Natural killer (NK) cells play a crucial role in limiting the severity of diseases caused by a range of viruses. Recent data have shown that the effector functions of NK cells can be specifically stimulated when NK cell activation receptors engage cellular major histocompatibility complex (MHC) class I-like ligands induced after infection or by specific viral gene products. However, to counter this NK cell response viruses have evolved an array of strategies to subvert efficient NK cell activation. These data indicate that the balance of host NK cell responses and viral NK cell escape mechanisms can be strategically poised as each strives for survival.
• PMID: 12377557 [PubMed - indexed for MEDLINE]

• Viral evasion of natural killer cells.

   

  <!--AuthorList-->Orange JS, Fassett MS, Koopman LA, Boyson JE, Strominger JL.

   

  Department of Molecular and Cellular Biology, Harvard University, Cambridge MA, USA.

   

  Viruses have evolved mechanisms to avoid the host immune system, including means of escaping detection by both the innate and adaptive immune responses. Natural killer (NK) cells are a central component of the innate immune system and are crucial in defense against certain viruses. To attain a state of chronic infection, some successful viruses have developed specific mechanisms to evade detection by and activation of NK cells. These NK cell-specific evasion mechanisms fall into distinct mechanistic categories used in numerous virus families.

   

  PMID: 12407408 [PubMed - indexed for MEDLINE]

• 1: Adv Cancer Res. 2003;90:127-56.<script language="JavaScript1.2"><!--  var Menu14710949 = [   ["UseLocalConfig", "jsmenu3Config", "", ""],  ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=14710949&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus&ordinalpos=1' ", "", ""],  ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=14710949&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""]  ]  --></script>

• Natural killer cells and cancer.

   

  <!--AuthorList-->Wu J, Lanier LL.

   

  Shanghai Gnomics, Inc., and Chinese National Genome Center, Shanghai, China.

   

  Natural killer (NK) cells are lymphocytes that were first identified for their ability to kill tumor cells without deliberate immunization or activation. Subsequently, they were also found to be able to kill cells that are infected with certain viruses and to attack preferentially cells that lack expression of major histocompatibility complex (MHC) class I antigens. The recent discovery of novel NK receptors and their ligands has uncovered the molecular mechanisms that regulate NK activation and function. Several activating NK cell receptors and costimulatory molecules have been identified that permit these cells to recognize tumors and virus-infected cells. These are modulated by inhibitory receptors that sense the levels of MHC class I on prospective target cells to prevent unwanted destruction of healthy tissues. In vitro and in vivo, their cytotoxic ability can be enhanced by cytokines, such as interleukin (IL)-2, IL-12, IL-15 and interferon alpha/beta (IFN-alpha/beta). In animal studies, they have been shown to play a critical role in the control of tumor growth and metastasis and to provide innate immunity against infection with certain viruses. Following activation, NK cells release cytokines and chemokines that induce inflammatory responses; modulate monocyte, dendritic cells, and granulocyte growth and differentiation; and influence subsequent adaptive immune responses. The underlining mechanism of discriminating tumor cells and normal cells by NK cells has provided new insights into tumor immunosurveillance and has suggested new strategies for the treatment of human cancer.

   

  PMID: 14710949 [PubMed - indexed for MEDLINE

• Nat Rev Microbiol. 2005 Jan;3(1):59-69.

• Viral modulation of NK cell immunity.

   

  <!--AuthorList-->Lodoen MB, Lanier LL.

   

  Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, 513 Parnassus Avenue, HSE 1001G, Box 0414, San Francisco, California 94143-0414, USA.

   

  Natural killer (NK) cells have been implicated in innate immune responses against viruses such as herpesviruses, which cause persistent infections in the host. In response to the selective pressure that is exerted by NK cells, many viruses have evolved strategies either to evade detection by NK cells or to modulate the activity of NK cells. Here, we review the unique relationship that exists between NK cells and viruses, with a focus on herpesviruses.

   

  PMID: 15608700 [PubMed - indexed for MEDLINE]

• Science. 2001 May 4;292(5518):934-7.

• Vital involvement of a natural killer cell activation receptor in resistance to viral infection.

   

  <!--AuthorList-->Brown MG, Dokun AO, Heusel JW, Smith HR, Beckman DL, Blattenberger EA, Dubbelde CE, Stone LR, Scalzo AA, Yokoyama WM.

   

  Howard Hughes Medical Institute, Rheumatology Division, Washington University School of Medicine, St. Louis, MO 63110, USA.

   

  Natural killer (NK) cells are lymphocytes that can be distinguished from T and B cells through their involvement in innate immunity and their lack of rearranged antigen receptors. Although NK cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based activation motif (ITAM)-containing transmembrane molecule for expression and signal transduction. Thus, NK cells use receptors functionally resembling ITAM-coupled T and B cell antigen receptors to provide vital innate host defense.

   

  PMID: 11340207 [PubMed - indexed for MEDLINE

• Blood. 2005 Mar 1;105(5):2028-35. Epub 2004 Nov 4
• Single-cell analysis of the human NK cell response to missing self and its inhibition by HLA class I.
• Draghi M, Yawata N, Gleimer M, Yawata M, Valiante NM, Parham P.

   

  Department of Structural Biology, Sherman Fairchild Building, 299 Campus Dr West, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.

   

  Natural killer (NK) cells activate quickly in response to pathogens, tumors, and allogeneic hematopoietic cell transplants. Modulating the NK cell response are clonally distributed NK cell receptors that survey cells for change in the expression of major histocompatibility complex (MHC) class I and structurally related ligands. Here the enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine staining (ICS), and short-term culture were used to quantify the response of bulk NK cell populations from human donors to HLA class I-deficient 221 cells and to 221 cells transfected with single HLA class I allotypes. NK cells in cultures containing interleukin-2 (IL-2) or IL-12 exhibited specificities of HLA class I-mediated inhibition that correlated well with those previously defined using NK cell clones in long-term culture and with the frequencies of cells expressing particular inhibitory HLA class I receptors. Culture with IL-12, but not IL-2, gave an increased frequency of cells expressing CD94: NKG2A but no change in killer immunoglobulin-like receptor (KIR) expression. For some heterozygote combinations of KIR3DL1 alleles, ICS can be used to compare the functional properties of the 2 allotypes. Thus, both the low-expressing KIR3DL1*005 and the high-expressing KIR3DL1*002 gave similar inhibitory response on challenge with an HLA-B*5801 ligand. The single-cell assays developed here should facilitate future population study and clinical analysis of human NK cell regulation by MHC class I.

   

  PMID: 15528315 [PubMed - indexed for MEDLINE]

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• : Microbes Infect. 2002 Dec;4(15):1523-30

• NK cell receptors: emerging roles in host defense against infectious agents.

   

  <!--AuthorList-->Robbins SH, Brossay L.

   

  Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Box G-B618, Providence, Rhode Island 02912, USA.

   

  Natural killer (NK) cells have the ability to become activated under the appropriate conditions by utilizing one or more cell surface receptors that are capable of inducing NK cell cytokine production and/or cytotoxicity. The expression of a variable array of inhibitory receptors on the surface of NK cells acts to counterbalance the positive signals initiated through activating receptors. Increasing evidence suggests an important role for both activating and inhibitory NK cell receptors in an appropriate and controlled NK response to infectious agents.

   

  PMID: 12505524 [PubMed - indexed for MEDLINE

• : Immunol Res. 2005;32(1-3):317-25.
• Natural killer cell immune responses.
• Yokoyama WM.

   

  Howard Hughes Medical Institute, Rheumatology Division, Department of Medicine, Washington University School of Medicine St. Louis, MO 63110, USA. yokoyama@wustl.edu

   

  Natural killer (NK) cells play a vital role in innate immune responses to infection; they express activation receptors that recognize virus-infected cells. Highly related to receptors recognizing tumor cells, the activation receptors trigger cytotoxicity and cytokine production. NK cells also express inhibitory receptors for major histocompatibility complex (MHC) class I molecules that block the action of the activation receptors. Although many ligands for NK cell receptors have MHC class I folds, recent studies also indicate ligands resembling the NK cell receptors themselves. A combination of immunologic, genetic, biophysical, and in vivo approaches is being employed to understand fully how these receptors contribute to NK cell activities in innate immunity to pathogens and tumors.

   

  PMID: 16106081 [PubMed - indexed for MEDLINE]

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• 1: Semin Hematol. 2005 Apr;42(2):91-103

• Natural killer cell receptors: regulating innate immune responses to hematologic malignancy.

   

  <!--AuthorList-->Hsu KC, Dupont B.

   

  Department of Medicine and Immunology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. hsuk@mskcc.org

   

  Critical to innate immunity, the natural killer (NK) cell performs its function of immunosurveillance through its recognition of altered or missing self on damaged, infected, or transformed malignant cells. NK cell receptors responsible for detection of human leukocyte antigen (HLA) class I and class I-like proteins on potential target cells transmit inhibitory and activating signals that integrate to determine NK cell function. Advances in the fields of NK cell receptor biology and immunogenetics have enhanced our understanding of NK cell target recognition and may now guide studies to determine NK cell effects in the clinical setting. Analysis of NK cell receptor-ligand relationships, such as the inhibitory killer immunoglobulin-like receptors (KIRs) and their HLA class I ligands, has revealed the potential for NK cell-mediated benefit in allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

   

  PMID: 15846575 [PubMed - indexed for MEDLINE]

• 1: Immunology. 2006 Jan;117(1):1-10.

• Putting the natural killer cell in its place.

   

  <!--AuthorList-->O'Connor GM, Hart OM, Gardiner CM.

   

  School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

   

  Natural killer (NK) cells were originally described as 'null' lymphocytes, but we have increasing evidence of their role in recognizing pathogen, and our knowledge of NK cell receptors continues to expand exponentially. Human NK cells have many receptors for human leucocyte antigen (HLA) class I. These killer immunoglobulin-like receptors (KIRs) and CD94/NKG2 receptors can signal in both positive and negative ways to regulate NK cell functions. The inhibitory receptors are the best characterized, but even in these cases much of their functional biology remains elusive. In this review, some recent advances in terms of the three-immunoglobulin (3Ig)-domain KIRs are discussed. Natural cytotoxicity receptors (NCRs) are among the activatory receptors found on NK cells. While pathogen ligands for these receptors have been described, endogenous ligands remain elusive. NCRs and NKG2D, a receptor for stress-induced antigens, appear to play complementary functional roles in terms of NK cell activation. More recently described on NK cells are the Toll-like receptors. In particular, these receptors of the innate immune system allow NK cells to directly sense pathogen, and their ligation on accessory cells indirectly activates NK cells through cytokine production. It is becoming clear that none of these receptor systems functions in isolation and that it is the sum of the signals (which will reflect the pathogenic situation), in addition to the cytokine milieu, that will direct NK cell activation. The resulting cytotoxicity, cytokine production and direct cell-cell regulatory interactions with other cells of the immune system, for example dendritic cells, ultimately determine the role of the NK cell in the context of an overall immune response.

   

  PMID: 16423035 [PubMed - indexed for MEDLINE]

• Development of natural killer cells from hematopoietic stem cells.
• Yoon SR, Chung JW, Choi I.

   

  Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Korea.

   

  Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from CD34+hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

   

  PMID: 17846493 [PubMed - indexed for MEDLINE

• Autoimmunity. 2004 Mar;37(2):147-53.
• The role of NK cells and NK cell receptors in autoimmune disease.
• Jie HB, Sarvetnick N.

   

  Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

   

  Natural killer (NK) cells are the first line of defense against infection and transformation. Additionally, NK cells can play seemingly opposite roles in autoimmune disease. Here, we summarize the functions of NK cells as both regulators and inducers of autoimmune disease. The role NK cells play depends on which cells become targets for NK cell attack. The activity of NK cells is controlled by inhibitory receptors specific for MHC Class I molecules, and by activating receptors with diverse specificities. The ligands for both activating and inhibitory receptors are present on potential target cells. It is the balance in expression of these different ligands that determines NK cell activation and therefore whether the cell becomes a target for NK cell-mediated killing. We further discuss the roles of NK cell receptors and their ligands in autoimmune disease.

   

  PMID: 15293884 [PubMed - indexed for MEDLINE]

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• Trends Immunol. 2005 Nov;26(11):613-8. Epub 2005 Aug 22.
• NK cells: elusive players in autoimmunity.

• Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden.

   

  Natural killer (NK) cells were once regarded as relatively simple cells of the innate immune system. However, they are now revealing themselves as multifunctional regulatory cells that are present throughout the body. The role of NK cells in autoimmunity is attracting increased attention, although the picture is clouded by a conflicting literature that presents disease-promoting as well as disease-protective roles. In this review, we discuss how NK cells might use these dual roles, and suggest that future studies should focus on the impact of the anatomical localization of NK cells as well as the cytokine environment in which NK cells act in individual autoimmune diseases.
• PMID: 16118064 [PubMed - indexed for MEDLINE]

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• 1: Autoimmun Rev. 2008 May;7(5):384-90. Epub 2008 Mar 31.<script language="JavaScript1.2"><!--  var Menu18486926 = [   ["UseLocalConfig", "jsmenu3Config", "", ""],  ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=18486926&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""]  ]  --></script>

• NK cells in autoimmunity: A two-edg'd weapon of the immune system.

   

  <!--AuthorList-->Perricone R, Perricone C, De Carolis C, Shoenfeld Y.

   

  University of Rome Tor Vergata, Rheumatology, Rome, Italy.

   

  Natural killer (NK) cells are part of the innate-immune system and respond rapidly to a variety of insults via cytokine secretion and cytolytic activity. Their main function is first line of innate immunity across viral, bacterial and parasitic infections. NK-cells are not solely killers but can also act as regulators of adaptive immunity. It is evident from literature that NK-cells are deeply involved in autoimmunity, but the question is how and why they act as a two edged weapon. Number of circulating NK-cells can be frequently altered depending on the disease taken into consideration. Cytokine milieu, the microenvironment in which they mature and other stimuli acting on different cell surface receptors may differently trigger NK-cells response and influence their role in autoimmune diseases. Functional differences between NK-cells at different anatomical sites, the adaptability of NK-cells effector responses and genetic factors may also explain differences in such responses. Thus, NK-cell alterations may be associated with increased autoimmunity and the modulation in the number of circulating NK-cells seems to be a primary event rather than an active inflammation/drug administration consequence during inflammatory/autoimmune processes, playing a fundamental role in the pathogenesis of a number of autoimmune diseases.

   

  PMID: 18486926 [PubMed - in process]