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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunobiology of human immunodeficiency virus (HIV) and the role of laboratory testing in the diagnosis and management of HIV infection are reviewed. HIV is one of a family of RNA viruses called retroviruses. HIV has three structural genes (one of which codes for reverse transcriptase) and six regulatory and maturation genes. Upon infection in humans, HIV commandeers the immune system by infecting and lysing T-helper lymphocytes. Since these cells are key to directing the body's immune defenses, the person becomes susceptible to a variety of opportunistic infections, neoplasias, and neurologic disorders. Laboratory tests for HIV are used for three purposes: screening of large populations (such blood donors), diagnosis of current or latent infection, and monitoring of disease progression. Diagnosis of HIV infection relies on HIV antibody detection, viral cultures, antigen detection, or polymerase chain reaction viral genome detection. Disease progression can be estimated using immunophenotyping with flow cytometry or using other immunologic markers. The immunologic variables associated with HIV infection disclose a growing spectrum of immune deficits. New tests for diagnosing and monitoring patients infected with HIV have been quickly incorporated into clinical practice.
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PMID:HIV infection: immunobiology and laboratory diagnosis. 1017 56

Pneumocystis carinii is a ubiquitous, atypical unicellular fungus. P. carinii pneumonia (PCP) is responsible for considerable morbidity and mortality in acquired immune deficiency syndrome (AIDS) patients, and is the leading complication in advanced human immunodeficiency virus (HIV) infection. Many different host (mammal)-specific species of Pneumocystis exist, but the life-cycle is not understood fully. Human strains are designated as P. carinii f. sp. (special form) hominis (at least 59 different types). P. carinii is spread via the airborne route. Disease is most frequently caused by fresh exposure to a source of P. carinii, rather than by reactivation of latent infection. Asymptomatic carriage among healthy persons may occur. PCP occurs in HIV-infected patients when the CD4+ count falls below a certain threshold; organisms multiply and gradually fill the alveoli. Symptoms, which include a mildly productive cough, progressive dyspnoea and fever, may persist for months prior to diagnosis. Without treatment, progressive respiratory insufficiency invariably ends in death. Pulmonary specimens may be obtained by procedures of varying sensitivity and risk. Diagnosis is usually confirmed by detection of stained organisms; however, staining procedures vary in sensitivity and ease of use. Robust polymerase chain reaction (PCR) protocols with good predictive results may be useful in the future. Therapy falls into two categories: for acute primary infections and for prophylaxis. A confirmed diagnosis ensures that patients do not receive potentially toxic medication (adverse drug reactions can occur). Prophylaxis can dramatically reduce the frequency of PCP in HIV patients, and its more widespread use should lead to a decline in the incidence of PCP in the future.
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PMID:Pneumocystis carinii infection in human immunodeficiency virus-positive patients. 1049 14

Central nervous system (CNS) toxoplasmosis is the most common cause of cerebral mass lesions in AIDS patients. Toxoplasma gondii is commonly acquired through ingestion of contaminated meats resulting in latent infection. With the onset of immunosuppression, it may preferentially infect the CNS, resulting in a wide range of clinical presentations. Effective antibiotic therapy is available and capable of producing rapid remission of active infection but must be continued throughout life to prevent recurrence. Characteristic presentations and rapid therapeutic response permit presumptive diagnosis and initiation of specific antibiotics in many cases; however, appropriate clinical and radiographic monitoring to detect alternative or mixed pathologies is necessary. Unusual presentations may hinder rapid diagnosis and should be considered in AIDS patients with cryptic CNS symptoms. Despite increasing attention to primary prophylaxis, the worldwide distribution of this parasite, its potential to be the presenting illness in previously unidentified human immunodeficiency virus-infected individuals, and failures of prophylaxis are likely to make toxoplasmosis an important continuing source of neurologic morbidity in AIDS.
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PMID:Neurologic manifestations of toxoplasmosis in AIDS. 1071 41

Human herpesviruses are characterized by distinct states of infection. Typically in permissive herpesvirus infection, abundant virus production results in cell lysis. In latent transforming Epstein-Barr virus (EBV) infection, viral proteins that induce cell growth are expressed. The immunodeficiency-associated hairy leukoplakia (HLP) lesion is the only pathologic manifestation of permissive EBV infection; however, within HLP, viral proteins characteristic of latent infection have also been detected. In this study, we further analyzed expression of EBV latent genes and investigated their contribution to the unique histologic phenotype of HLP. Coexpression of lytic and transforming viral proteins was detected simultaneously within individual HLP keratinocytes. LMP1 has now been shown to be uniformly expressed in the affected tissue, and it is associated and colocalizes with tumor necrosis factor receptor-associated factor (TRAF) signaling molecules. Effects induced by activated TRAF signaling that were detected in HLP included activation of NF-kappaB and c-Jun terminal kinase 1 (JNK1) and upregulated expression of epidermal growth factor receptor (EGFR), CD40, A20, and TRAFs. This study identifies a novel state of EBV infection with concurrent expression of replicative and transforming proteins. It is probable that both replicative and latent proteins contribute to HLP development and induce many of the histologic features of HLP, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV transforming proteins within the permissively infected HLP tissue enables epithelial cell survival and may enhance viral replication.
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PMID:Hairy leukoplakia: an unusual combination of transforming and permissive Epstein-Barr virus infections. 1090 15

Latently infected resting CD4(+) T cells provide a long-term reservoir for human immunodeficiency virus type 1 (HIV-1) and are likely to represent the major barrier to virus eradication in patients on combination antiretroviral therapy. The mechanisms by which viruses enter the latent reservoir and the nature of the chemokine receptors involved have not been determined. To evaluate the phenotype of the virus in this compartment with respect to chemokine receptor utilization, full-length HIV-1 env genes were cloned from latently infected cells and assayed functionally. We demonstrate that the majority of the viruses in the latent reservoir utilize CCR5 during entry, although utilization of several other receptors, including CXCR4, was observed. No alternative coreceptors were shown to be involved in a systematic fashion. Although R5 viruses are present in the latent reservoir, CCR5 was not expressed at high levels on resting CD4(+) T cells. To understand the mechanism by which R5 viruses enter latent reservoir, the ability of an R5 virus, HIV-1 Ba-L, to infect highly purified resting CD4(+) T lymphocytes from uninfected donors was evaluated. Entry of Ba-L could be observed when virus was applied at a multiplicity approaching 1. However, infection was limited to a subset of cells expressing low levels of CCR5 and markers of immunologic memory. Naive cells could not be infected by an R5 virus even when challenged with a large inoculum. Direct cell fractionation studies showed that latent virus is present predominantly in resting memory cells but also at lower levels in resting naive cells. Taken together, these findings provide support for the hypothesis that the direct infection of naive T cells is not the major mechanism by which the latent infection of resting T cells is established.
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PMID:Characterization of chemokine receptor utilization of viruses in the latent reservoir for human immunodeficiency virus type 1. 1093 89

Tuberculosis is the commonest opportunistic infection in HIV-infected patients in developing countries including India. The seroprevalence of HIV among tuberculosis patients in various parts of India has been increasing steadily. Children who are HIV-infected have a higher risk of progression after primary infection. Children born to HIV positive parents who are not infected themselves are also at higher risk of acquiring tuberculosis because of exposure. The clinical and radiological manifestations of tuberculosis are similar to those seen in HIV-uninfected individuals, except in those with advanced immunodeficiency. Most patients respond well to standard chemotherapy but mortality remains high because of other opportunistic infections. Preventive treatment with isoniazid for 6-12 months is effective in reducing those with latent infection.
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PMID:Tuberculosis with human immunodeficiency virus infection. 1112 8

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.
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PMID:Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients. 1159 23

31 children aged 1 to 9 years with malformations of the kidneys and upper urinary tracts were preoperatively examined for immune status. After plastic operation 14 children developed early postoperative infectious-inflammatory complications. It is suggested that early postoperative complications in some children with renal and upper urinary tract maldevelopments may arise because of weak compensatory abilities and immunodeficiency resultant from the operative stress. These created favourable conditions for activation of latent infection. Immunological assessment of the patient prior to surgery predicts early postoperative complications and thus enables proper preventive measures.
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PMID:[Immunity status in early postoperative complications in children with anomalies of kidneys and upper urinary tract]. 1123 30

The latency-associated nuclear antigen (LANA) is constitutively expressed in cells infected with the Kaposi's sarcoma (KS) herpesvirus (KSHV), also referred to as human herpesvirus 8. KSHV is tightly associated with body cavity-based lymphomas (BCBLs) in immunocompromised patients infected with human immunodeficiency virus (HIV). LANA, encoded by open reading frame 73 of KSHV, is one of a small subset of proteins expressed during latent infection and was shown to be important in tethering the viral episome to host chromosomes. Additionally, it has been shown that LANA can function as a regulator of transcription. However, its role in the progression of disease is still being elucidated. Since KS is one of the most common AIDS-associated cancers in the United States and BCBLs appear predominantly in AIDS patients, we examined whether LANA is able to regulate the HIV type 1 (HIV-1) long terminal repeat (LTR). Using luciferase-based transient transfection assays, we found that LANA was able to transactivate the HIV-1 LTR in the human B-cell line BJAB, human monocytic cell line U937, and the human embryonic kidney fibroblast cell line 293T. Moreover, we observed that the virus-encoded HIV transactivator protein Tat cooperated with LANA in activation of the LTR in a dose-response fashion with increasing amounts of LANA. Surprisingly, LANA alone was sufficient to transactivate the HIV-1 LTR in BJAB cells. In similar assays using a HIV-1 LTR construct with the core enhancer elements deleted; the activity of LANA was diminished but not abolished, indicating a mechanism which involves the cooperation of the core enhancer elements and downstream elements which include Tat. Furthermore, transient transfection of an infectious clone of HIV with LANA demonstrated effects similar to those seen in the reporter assays based on Western blot analysis of HIV Gag polypeptide p24. Interestingly, we also demonstrated that the carboxy terminus of LANA associates with Tat in cells and in vitro. These experiments suggest a role for LANA in activating the HIV-1 LTR through association with cellular molecules targeting the core enhancer elements and Tat and may have important consequences in increasing the levels of HIV in infected individuals and, hence, the disease state.
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PMID:Latency-associated nuclear antigen encoded by Kaposi's sarcoma-associated herpesvirus interacts with Tat and activates the long terminal repeat of human immunodeficiency virus type 1 in human cells. 1150 21

Although plasma virus load is invaluable for monitoring human immunodeficiency virus (HIV) infection, key pathogenesis events and most viral replication take place in lymphoid tissues. Decreases in virus load associated with therapy occur in plasma and tissues, but persistent latent infection and ongoing viral replication are evident. Many unanswered questions remain regarding mechanisms of HIV-associated lymphocyte depletion, but partial CD4(+) cell reconstitution after therapy likely reflects retrafficking from inflamed tissues, increased thymic or peripheral production, and decreased destruction. Rapid establishment of latent infection and the follicular dendritic cell-associated viral pool within lymphoid tissues suggest that only early intervention could substantially alter the natural history of HIV. If therapy is started prior to seroconversion, some individuals retain potent HIV-specific cellular immune responsiveness that is suggestive of delayed progression. Although complete virus eradication appears out of reach at present, more attention is being directed toward the prospect of boosting HIV-specific immune responses to effect another type of "clinical cure": immune-mediated virus suppression in the absence of therapy.
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PMID:Human immunodeficiency virus pathogenesis: insights from studies of lymphoid cells and tissues. 1151 93


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