Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms causing nonresponsiveness to hepatitis B surface Ag (HBsAg) vaccines in humans remain largely unknown. The increased incidence of nonresponsiveness in subjects with HLA-DR3 or -DR7 haplotype suggests that immune response mechanisms governed by genes of the MHC are involved. It is conceivable that APC of nonresponders are defective in the presentation of HBsAg because they are unable to adequately take up, process, or present this Ag. To examine this hypothesis we have used PBMC from nonresponders to present recombinant particles containing S or PreS2-S sequences to HBsAg-specific T cell lines from haplo-identical responder vaccinees. The proliferative response of these lines was used to evaluate the efficacy of Ag presentation. Unfractionated PBMC from five DR2+ and six DR7+ nonresponders did not proliferate to HBsAg in vitro, whereas they vigorously proliferated upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. All DR2(15)+ nonresponders were able to present hepatitis B envelope Ag to HBsAg-specific, DR1501-restricted T cells. PBMC from six DR7+ nonresponders were all able to present HBsAg to DR07-restricted T cell lines and PBMC from three DPw4+ nonresponders were able to present HBsAg to DP0402-restricted T cell lines. Additional experiments showed that PBMC from two nonresponders presented HBsAg equally well and sometimes better than PBMC from two partially HLA-matched high responders. We conclude that HLA-DR2+, -DR7+, and -DPw4+ nonresponder vaccinees are able to take up, process and present HBsAg to allogeneic, haplo-identical T cell lines in vitro.
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PMID:Nonresponders to hepatitis B vaccine can present envelope particles to T lymphocytes. 781 65

The anti-retrovirus cell-mediated immunity was repeatedly investigated in seven monkeys (Macaca sylvana). Four of these animals were injected with cell-free supernatants containing human immunodeficiency viruses: two monkeys received HIV1 Bru (2.5 x 10(6) cpm), two received HIV2 Rod (1.5 x 10(6) cpm). Two additional animals were injected with a cell-free supernatant containing simian immunodeficiency virus SIV/mac 251 (1.5 x 10(6) cpm) and the last animal served as control. The four macaques infected with HIV2 Rod and SIV/mac 251 seroconverted. Freshly isolated and non stimulated peripheral blood mononuclear cells from these infected macaques and from the uninfected control were repeatedly assessed for cytolytic activity. Target cells consisted of heterologous human cell lines expressing HIV1 Bru, HIV2 Rod or SIV/mac proteins. A significant cytotoxic activity, non-restricted at the major histocompatibility complex class I (MHC-I), was demonstrated in one HIV2 Rod-infected animal (F8) and in one SIV/mac 251-infected animal (M1). This last animal showed progressively diminishing cytolytic activity that was correlated with a pronounced decrease in CD4+ lymphocytes. An AIDS-like disease developed in M1, with presence of lymphadenopathy, weight loss, diarrhea and opportunistic infections. Cytotoxic activity was active against SIV and HIV2-infected target cells in an MHC-unrestricted manner; it was specific to virus-infected cells and there was cross-reactivity between HIV2 and SIV. Cytotoxic effectors appeared to be mainly CD8+ cells. This model may prove to be very useful in evaluating the capacity of candidate AIDS vaccines to elicit effective cell-mediated immune responses.
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PMID:MHC-I non-restricted cytotoxic activity in Macaca sylvana experimentally inoculated with HIV2 and SIV/mac. 790 83

Cell-mediated immune responses are a major immune defence mechanism against the spread of human immunodeficiency virus type 1 (HIV-1) which may lead to acquired immune deficiency syndrome (AIDS). Therefore, the best candidate for a peptide vaccine preventive from the onset of the disease might be a chain section containing both B- and T-cell epitopes in regions of conserved sequences between the different HIV-1 isolates. We previously identified the highly conserved linear B-cell epitope (23 amino acids in the major core protein p24). Since the epitopes of cytotoxic T lymphocytes (CTLs) can be defined by short synthetic peptides, we examined whether this highly conserved region can elicit viral-specific, cell-mediated immune responses. The results showed specific induction of CD8+ CTLs in mice by immunization with the Gag 13-mer peptide. Lysis of targets is specific since unpulsed cells with the same MHC haplotype or cells with a different MHC haplotype pulsed with the peptide were resistant to lysis. This in vivo response induced by the Gag 23-mer peptide was almost the same as that induced by the 15-amino acid peptide from the HIV-1 Env gp120 which is an immunodominant domain in the V3 loop. Lymphocyte proliferation of T-cell fraction from immune spleen cells was observed after in vitro stimulation with the Gag 23-mer peptide, whereas there was no apparent lymphocyte proliferation with the Env 15-mer peptide. In addition, specific antibodies were raised against Gag p24 in mice immunized with the Gag 23-mer peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo induction of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes and delayed-type hypersensitivity by a 23-amino acid peptide from the highly conserved region in major core protein p24. 791 66

Specific pathogen-free cats were experimentally infected with feline immunodeficiency virus (FIV) and subsequently exposed to common infectious pathogens and immune stimuli over a 3-year period. Cats with preexisting FIV infection showed signs of disease after exposure to Haemobartonella felis, Toxoplasma gondii, feline herpesvirus-1, and feline calicivirus similar to signs in non-FIV-infected cats, although they were more severe. No adverse effects of immunization with inactivated rabies virus vaccine and a synthetic polyproline immunogen were observed in either FIV-infected or non-FIV-infected cats, whereas the application of a diphtheria-tetanus-pertussis vaccine caused transient fever and lymphadenopathy in both groups of animals. Primary immune responses to pathogens or immunogens were usually delayed or diminished in FIV-infected compared with non-FIV-infected cats. Repeated infections and immune activation had no significant effects on the levels of FIV-specific antibodies or on the proportion of peripheral blood mononuclear cells (PBMCs) containing FIV proviral DNA. However, FIV-infected cats that were not exposed to immune stimuli had lower CD4+ T-lymphocyte numbers and lower CD4+/CD8+ T lymphocyte ratios at the end of the 3-year study than FIV-infected cats exposed to cofactors. The latter also had normal levels of interleukin-3 receptor (IL-2R) and major histocompatibility class II (MHC-II) antigen expression on PBMCs, while FIV-infected cats not exposed to cofactors had up-regulated IL-2R and down-regulated MHC-II antigen expression. It was concluded that repeated immune stimulation did not have a deleterious effect on the course of FIV-induced immunodeficiency.
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PMID:Effects of incidental infections and immune activation on disease progression in experimentally feline immunodeficiency virus-infected cats. 791 48

We have studied the putative roles of human immunodeficiency virus (HIV)-associated and cell surface-expressed major histocompatibility complex class I (MHC-I) molecules in the course of the HIV life cycle by the combined use of MHC-I molecule-positive and MHC-I molecule-negative virus particles and MHC-I molecule-positive and MHC-I molecule-negative CD4+ human cells. We found (i) that several anti-MHC-I monoclonal antibodies neutralize cell infection by direct interaction with HIV-associated MHC-I antigens, (ii) that these HIV-associated MHC-I antigens are however dispensable for cell infection, and (iii) that the cell surface-expressed MHC-I molecules are unnecessary for productive infection of CD4+ human cells. These results clarify further the functions of MHC-I molecules during the HIV life cycle.
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PMID:Involvement of human leukocyte antigen class I molecules in human immunodeficiency virus infection of CD4-positive cells. 791 59

A dynamical model for an N-terminal fragment of the human CD4 protein has been determined by computer simulation. The protein has been studied both in vacuo and in solution. Data from both simulations agree moderately well with each other and with the crystal structure. All elements of secondary structure were retained during simulation. Point mutation and sequence replacement studies have shown that a loop in CD4, residues 40-52 is involved in binding with gp120, the human immunodeficiency virus surface glycoprotein. Our results show that the gp120-binding loop and a few regions which bind to monoclonal antibodies and class II MHC molecules are the most highly motile areas of the protein. These results are consistent with the suggestion that CD4 binds to target molecules by using induced-fit contacts.
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PMID:Molecular dynamics studies of the human CD4 protein. 794 28

Early in human immunodeficiency virus (HIV) infection CD4+ and CD8+ T cells are qualitatively affected. Loss of responses to recall antigen precedes impaired responses to allogeneic MHC and mitogens. The selective quantitative loss of memory T cells in early infection, only partially explains the observed defects. We investigated whether functional loss of T cells is preferentially observed for memory T cells or whether both naive and memory T cell subsets are affected in the course of HIV infection. We studied the proliferative response of CD4+ T cells from HIV-infected individuals to alloantigens, to which normally both naive and memory T cells respond, by limiting dilution analysis. The decreased proliferative response to alloantigens in HIV-infected individuals was associated with a decreased precursor frequency of alloreactive cells. The frequency was decreased in both the CD45RA+ (naive) and the CD45RO+ (memory) subset of CD4+ T cells. Analysis of four individuals in the course of HIV infection revealed similar kinetics of the decline in function in both subsets. Although initially T cell defects may be accounted for by the selective quantitative loss of memory cells, in later stages of HIV infection the function of both CD45RA+ and CD45RO+ cells is affected.
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PMID:Quantitative analysis of CD4+ T cell function in the course of human immunodeficiency virus infection. Gradual decline of both naive and memory alloreactive T cells. 796 40

An extensive genetic and physiological analysis of the cheetah by O'Brien et al. (1983; 1985; 1987) indicated that the cheetah showed monomorphism at the major histocompatability complex. This led O'Brien (1985) to propose that the cheetah suffered from an immunodeficiency and was highly susceptible to diseases. It was therefore decided to investigate cell-mediated and humoral immune responses and to apply the limited restriction fragment length analysis (using Pst 1 and Bam H1 enzymes) of the cheetah MHC I and MHC II genes. Antibody responses to antigens (feline viruses), as well as mitogen-induced lymphocyte blast transformation responses, were shown to be intact and comparable with that of the domestic cat, indicating a competent immune system in the cheetah. It was also suggested by the results that some polymorphism does exist in the MHC class II genes, but possibly not in the MHC class I genes.
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PMID:Lymphocyte blast transformation responses and restriction fragment length analysis in the cheetah. 797 May 77

CD4 cross-linking by antibodies or its natural ligands triggers a tyrosine kinase activity that is one of the necessary steps in the mechanism of human immunodeficiency virus type 1 (HIV-1)-induced syncytium formation and full Th-cell activation. In this study we mapped a part of the dimerization site of human CD4 to amino acids 87-98 using a bivalent CD4 immunoadhesin and a series of overlapping 12-mer peptides of the D1 domain. The dimerization site we found is part of the complementary determining region (CDR) 3-like region of CD4. Using the three-dimensional structure of other immunoglobulin dimers as a basis, a molecular modeling study was performed to dimerize the D1 domains of CD4. Both the peptide binding studies and molecular modeling studies independently led to the conclusion that the CDR3-like region is part of the CD4 dimerization site. The suggested dimerization of CD4 through its CDR3-like region explains the important role that has been ascribed to this region in Th-cell activation and HIV-1-mediated fusion. Based on this model of the CD4 dimer and published results of different mutational analysis studies, a model was proposed for the complex of the CD4 dimer with two MHC-II molecules. The CD4 dimer allows tight binding to a large surface of MHC-II and the complex of CD4 and MHC-II reconciles mutational analysis studies that were previously incompatible. Moreover, the complex suggests how CD4 can dimerize through ligand binding.
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PMID:Location of CD4 dimerization site explains critical role of CDR3-like region in HIV-1 infection and T-cell activation and implies a model for complex of coreceptor-MHC. 804 41

Replication of the human immunodeficiency virus (HIV) in CD4+ cells is suppressed in the presence of CD8+ cells from asymptomatic HIV-infected individuals. Although these CD8+ cells mediate HIV-specific, class I MHC restricted CTL activity, the predominant mechanism for inhibiting virus replication requires neither contact nor MHC matching between the CD8+ effector cells and CD4+ targets. Based on these data, a model involving two tiers of control on HIV replication by CD8+ cells is proposed. The first level would be mediated by a diffusible CD8+ cell-derived factor that prevents expression of the retroviral genome in a non-MHC restricted fashion. When this transcriptional control is lost, production of HIV proteins would sensitize the cell for lysis by class I MHC restricted, virus-specific CTL.
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PMID:Non-cytolytic control of HIV replication by CD8+ T cells. 810 64


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