Immunodeficiency reviews最新文献

Gene therapy for primary immunodeficiency disease. 原发性免疫缺陷疾病的基因治疗。

Immunodeficiency reviews Pub Date : 1992-01-01

R M Blaese, K W Culver

{"title":"Gene therapy for primary immunodeficiency disease.","authors":"R M Blaese, K W Culver","doi":"","DOIUrl":"","url":null,"abstract":"Gene therapy offers the potential for developing innovative new treatments for both inherited monogenic diseases as well as polygenic and acquired disorders. For most potential clinical applications, the technology has not yet progressed to the stage where it might be reasonably tested. Problems to be solved include the isolation and characterization of the genes involved, the development of gene delivery systems that will permit efficient gene insertion in the affected cells and tissues, and the development of mechanisms to control or appropriately regulate expression of the introduced genes. The primary immunodeficiency diseases as a group actually lend themselves to the development of gene therapy strategies with current technology more readily than almost any other class of disease. Theoretically any genetic disease that can be successfully treated by allogeneic bone marrow transplantation is a potential candidate for gene therapy directed at correcting the patient's own totipotent bone marrow stem cells. In addition, some disorders lend themselves to genetic correction of more mature cells, although gene transfer in this treatment strategy might have to be repeated periodically. The rationale and preliminary results of the first gene therapy protocol for ADA deficiency SCID are described and strategies for developing somatic cell gene therapy for the other primary immunodeficiency diseases are discussed.","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 4","pages":"329-49"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular basis of the autosomal recessive forms of chronic granulomatous disease. 慢性肉芽肿病常染色体隐性遗传的分子基础。

Immunodeficiency reviews Pub Date : 1992-01-01

J T Curnutte

{"title":"Molecular basis of the autosomal recessive forms of chronic granulomatous disease.","authors":"J T Curnutte","doi":"","DOIUrl":"","url":null,"abstract":"Chronic granulomatous disease (CGD) is an inherited group of disorders in which phagocytic leukocytes (neutrophils, eosinophils, monocytes, and macrophages) fail to undergo a respiratory burst when stimulated. The products of the respiratory burst, which include superoxide and hypochlorous acid, play a critical role in killing pathogenic bacteria, fungi, and parasites. As a result of the failure to activate the respiratory burst in their phagocytes, most CGD patients suffer from severe recurrent infections. While all CGD patients share this severe defect, there is substantial heterogeneity in the molecular mechanisms responsible. The enzyme that catalyzes the respiratory burst, NADPH oxidase, has been extensively characterized and found to consist of at least four subunits: gp91-phox and p22-phox (the two subunits of a low potential cytochrome b that is the terminal electron carrier of the oxidase) as well as p47-phox and p67-phox (two cytosolic oxidase components). CGD is caused by a defect in any one of these four components, thus explaining the previously confusing genetic heterogeneity of this disorder. In approximately thirty reported cases, the underlying mutations involving these oxidase components have been identified. The current understanding of the molecular basis of CGD is reviewed in the context of a recently completed Phase III clinical trial establishing the efficacy of recombinant human interferon gamma in the treatment of CGD.","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 2","pages":"149-72"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12722300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nonhuman primate models for HIV vaccine development. HIV疫苗开发的非人类灵长类动物模型。

Immunodeficiency reviews Pub Date : 1992-01-01

N L Letvin

引用次数: 0

Primary immunodeficiency diseases. Report of a WHO scientific group. 原发性免疫缺陷病。世卫组织科学小组的报告。

Immunodeficiency reviews Pub Date : 1992-01-01

引用次数: 0

Severe combined immunodeficiencies. 严重的联合免疫缺陷。

Immunodeficiency reviews Pub Date : 1992-01-01

A Fischer

引用次数: 0

Immunological abnormalities in the natural history of HIV infection: mechanisms and clinical relevance. HIV感染自然史中的免疫异常:机制和临床相关性。

Immunodeficiency reviews Pub Date : 1992-01-01

F Miedema

{"title":"Immunological abnormalities in the natural history of HIV infection: mechanisms and clinical relevance.","authors":"F Miedema","doi":"","DOIUrl":"","url":null,"abstract":"Infection with the human immunodeficiency virus (HIV) ultimately results in profound immunodeficiency characterized by severe depletion of CD4+ T helper cells. In symptomatic infection a general perturbance of immune function is observed. Here recent insights in the sequence of events in progression to AIDS is reviewed. Following seroconversion a rapid persistent loss of inducible B cell function is observed. In addition, in long term infection, antigen-presenting cell functions of monocytes and dendritic cells are increasingly affected. T-cell non-responsiveness, preceding CD4 cell loss, appears to be induced through several different, sequential mechanisms. In early infection, the in-vivo deletion of memory cells can account for the in-vitro decreased responsiveness. Later on in infection, when the balance between memory and naive T cells is normalized, both CD4 and CD8 cells are non-responsive to nominal antigen and low dose anti-CD3 monoclonal antibodies. This anergy is at the level of IL-2 gene expression since early signal transduction events following CD2 and CD2 receptor occupancy are normal. This state of anergy, probably due to inappropriate activation in vivo, may be related to programmed cell death (PCD) observed in vitro for both CD8 and CD4 cells reflecting a systemic interference with maturation and differentiation of T cells. In progression to symptomatic infection, the proportion of non-responsive CD8 cells with immature or activated phenotypes increases and in about fifty percent of the cases, CD4 cell decline may accelerate in association with emergence of syncytium-inducing HIV variants. During this progressive stage, anti-CD3 reactivity is severely decreased, and alloantigen reactivity and finally the capacity to respond to phytohemagglutinin (PHA) are affected. These functional parameters appear useful for staging of HIV-infected individuals and for evaluation of anti-viral therapy.","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 3","pages":"173-93"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12528561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The programmed cell death theory of AIDS pathogenesis: implications, testable predictions, and confrontation with experimental findings. 艾滋病发病机制的程序性细胞死亡理论:含义，可测试的预测，以及与实验结果的对抗。

Immunodeficiency reviews Pub Date : 1992-01-01

J C Ameisen

引用次数: 0

Domestic animal models of severe combined immunodeficiency: canine X-linked severe combined immunodeficiency and severe combined immunodeficiency in horses. 严重联合免疫缺陷的家养动物模型:犬x连锁严重联合免疫缺陷和马严重联合免疫缺陷。

Immunodeficiency reviews Pub Date : 1992-01-01

P J Felsburg, R L Somberg, L E Perryman

引用次数: 0

Perinatal HIV transmission facts and controversies. 围产期艾滋病毒传播的事实和争议。

Immunodeficiency reviews Pub Date : 1992-01-01

J F Delfraissy, S Blanche, C Rouzioux, M J Mayaux

{"title":"Perinatal HIV transmission facts and controversies.","authors":"J F Delfraissy, S Blanche, C Rouzioux, M J Mayaux","doi":"","DOIUrl":"","url":null,"abstract":"In 1992, HIV infection in children is essentially due to vertical or perinatal transmission, i.e. from the mother to the fetus and neonates. This is a particularly serious public-health problem in Africa where the percentage of infected women of child bearing age is as high as 20% in some suburban areas. During the last few years, three important points have been established. (i) In Europe and North America, the rate of perinatal transmission is between 15 and 25% and appears to have remained relatively stable with time in various prospective cohorts. (ii) Considerable efforts have been directed at defining the optimal methods for early diagnosis of HIV infection in the infants. At present viral cultures and gene amplification of HIV DNA by polymerase chain reaction are the most promising procedures for early diagnosis within the first 6 months of life. (iii) Finally, the course of the disease in the infected infant has been well characterised, it takes two main forms--that of an early and severe disease or that of a slowly progressive infection: In addition, follow-up is now sufficient to confirm that children with negative tests at 15 months are indeed uninfected. However, knowledge is lacking in a number of essential areas. These include the exact timing of transmission (in utero, during delivery or post-partum), the relative frequency of transmission during each period, the mechanism(s) involved (particularly the role of the placenta), and, finally, the influence of maternal, fetal and viral factors. Answers must be found rapidly in order to develop preventive therapy, to identify women who may have an increased risk of transmitting the virus, to develop a reliable antenatal diagnostic test and, finally, to be in a better position to inform HIV-seropositive women of the relative risks.","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 4","pages":"305-27"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inherited deficiencies of the terminal components of human complement. 人类补体末端成分的遗传性缺陷。

Immunodeficiency reviews Pub Date : 1992-01-01

R Würzner, A Orren, P J Lachmann

{"title":"Inherited deficiencies of the terminal components of human complement.","authors":"R Würzner, A Orren, P J Lachmann","doi":"","DOIUrl":"","url":null,"abstract":"The particularly frequent occurrence of terminal complement deficiencies in patients with Neisserial infections suggests that the cytolytic activity of the complement system is important in resistance to Neisseria meningitidis. There are, however, geographical differences in the prevalence of terminal complement deficiency in patients with meningococcal disease. The data available suggest that either recurrent infection or infection with uncommon serogroups should alert the clinician in Western countries whereas recurrent disease is the important indicator in high risk endemic or epidemic areas. An association of terminal complement deficiencies with susceptibility to autoimmune diseases or non-Neisserial infections is doubtful. For a better understanding of complement deficiencies in relation to disease more accurate characterization of the defects involved will be helpful. Sensitive ELISA techniques and molecular biological assays will be needed. Thus it has been established that two types of deficiencies exist (at least for C6, C7 and C8): one with low but detectable amounts of the component and the other with a complete absence of the protein in question. The subtotal variety appears to show less association with Neisserial infection. Low amounts of functional terminal complement activity may be sufficient for many of its biological functions, suggesting that there is a wide \"safety margin\".","PeriodicalId":77170,"journal":{"name":"Immunodeficiency reviews","volume":"3 2","pages":"123-47"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12722962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0