Cellular immune response in virus infections

Two levels of specificity exist in the killing of virus infected target cells by immune effector T cells. One relates to the classic specificity for the virus, and the second involves the necessity for sharing expression of genes mapping in K and D but not I regions. Among the theories that could explain this is that of dual recognition with separate T-cell receptors detecting H-2 and viral antigen. Support for this possibility was provided by experimental influenza virus infection where evidence of specific recognition of viral products was obtained.     

Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis

Candida albicans mannan extracts encapsulated in liposomes were previously used to stimulate mice to produce antibodies protective against candidiasis. In the present study, mannan-protein conjugates without liposomes were tested as vaccine candidates. Mannan extracts were coupled to bovine serum albumin, and isolated conjugates consisted of carbohydrate and protein at a ratio of 0.7-1.0. Vaccination of mice with the conjugate and an adjuvant yielded antiserum that contained Candida agglutinins. Vaccinated mice challenged with yeast cells had a mean survival time of 56 days, compared with <13 days for control groups. The antiserum protected naive animals against disseminated disease. Naive mice given the antiserum intravaginally developed 79% fewer fungal colony-forming units, compared with control groups. The serum-protective factor was stable at 56 degrees C and was removed by adsorption with yeast cells. It is concluded that the conjugate vaccine can induce protective antibody responses against experimental disseminated candidiasis and Candida vaginal infection.     

Human cellular immune response to Giardia lamblia

Summary Human peripheral blood mononuclear cells (PBMC) from two individuals experimentally and one naturally infected withGiardia lamblia responded strongly (in anin vitro lymphocyte proliferation assay) to both heterologous and homologous (parasite origin)G. lamblia antigen stimuli. Proliferative responses to specific antigens as determined by T-cell blotting were due toGiardia T-cell epitopes mostly present in antigens lower than M_r 85,000 and 31,000 in isolates PM and GS/M-H7, respectively. Additionally, Il-2 production of PBMC respective to T lymphocyte subsets under antigen stimulation were determined in one selected patient. Proliferative and lymphokine responses could be associated with CD4⁺ PBMC depleted of CD8⁺ T cells and not with PBMC depleted of CD4⁺ T cells. These preliminary results suggest the initiation of larger studies addressing questions of cell-mediated immune response and the role of lymphokines in human giardiasis.

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Zelluläre Immunreaktion gegen Giardia lamblia beim Menschen

Zusammenfassung Periphere Blutmonozyten von zwei Personen mit einer experimentell und einer mit einer natürlich erworbenenGiardia lamblia-Infektion zeigten eine ausgeprägte lymphoproliferative Antwort nachIn-vitro-Stimulation mit Parasitenantigen, das sowohl aus homologen als auch heterologen Parasitenisolaten gewonnen worden war. Eine T-Zell-Blot- Analyse der lymphoproliferativen Immunantwort bezüglich der nach Molekulargewicht aufgetrenntenGiardia-Antigenkomponenten zeigte, daß das Spektrum derGiardia-Antigene mit T-Zell-Epitopen im M_r-Bereich von < 85'000 für das PM-1-Isolat und < 31'000 für das GS/M-H7-Isolat lagen. Bei einem der Patienten wurden Lymphozyten nach antigen-spezifischerIn-vitro-Proliferation auf ihre Lymphozytensubpopulationen und deren Fähigkeit zur Il-2-Produktion untersucht. Eine lymphoproliferative Antwort, verkoppelt mit einer Il-2-Produktion, war nur bei CD4⁺ Lymphozyten (nach entsprechender Eliminierung von CD8⁺ Lymphozyten) und nicht bei CD8⁺ Lymphozyten (nach entsprechender Eliminierung von CD4⁺ Lymphozyten) nachweisbar.

     

Human immune response and Chlamydia trachomatis infection

Chlamydia trachomatis is a prevalent pathogen in human populations in both developing and developed areas of the globe. Disease burden is heavy, since both acute and chronic complications can arise from infection. Emerging knowledge of the immune response to infection suggests that many of the complications of chlamydial infection are accompanied by important alterations in immunoregulation; new information suggests that both antibody-mediated and cell-mediated immune effectors may be significant in eliminating or limiting chlamydial infection. Further studies of the pathophysiologic mechanisms of host defense and the ways in which C. trachomatis escapes these defenses are needed. Elucidation of the immune response may provide the information necessary to redevelop a vaccine approach to disease control.     

狂犬病病毒感染免疫反应研究进展

狂犬病病毒感染机体后可引起严重的脑炎,病死率几乎为100%。暴露前预防免疫和及时的暴露后免疫可有效阻止脑炎的发生,一旦出现狂犬病临床症状后,几乎所有的治疗方法均无效。病毒感染机体后,激发机体产生先天性和获得性免疫应答,而在病毒进入中枢神经系统前,机体产生的免疫应答不足可能是免疫保护失败的原因之一。本文综述了机体对狂犬病病毒感染与疫苗免疫产生的免疫反应。     

Vaccination with a live retrovirus: the nature of the protective immune response.

We tested 3'-azido-3'-deoxythymidine (zidovudine) combined with interferon alpha as chemoprophylaxis after exposing mice to Rauscher murine leukemia virus. Therapy started 4 hr after inoculation and administered for 20 days prevented viremia and disease in all 234 mice tested. When the animals were rechallenged with live virus after cessation of therapy, 96% were resistant. The nature of this protective immune response was analyzed: Passive serotherapy of naive mice challenged subsequently with Rauscher murine leukemia virus was only protective at a high dose of immune serum. Immune, but not naive, T cells alone were fully protective against virus challenge. We conclude that vaccination with a live retrovirus that cannot replicate because of pharmacological blockade induces a T-cell response capable of protecting against a lethal retrovirus-induced disease.     

Human immune repertoire in hepatitis B virus infection

Hepatitis B virus (HBV) infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis, liver failure, and hepatocellular carcinoma. The HBV antigen- induced adaptive immune response plays an important role in HBV clearance. Immune repertoire sequencing (IRS) has been used to investigate the molecular mechanisms behind the immune system, find novel ways to treat HBV infection, and evaluate the genetic responses and immune characteristics of individuals infected by HBV or immunized by HBV vaccine. This review summarizes the human immune repertoire analysis methodology, and the application of the IRS in the prediction of HBV infection progression, treatment, and vaccination.     

Adaptive immune response during hepatitis C virus infection

Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.     

Cellular immune response to the hepatitis C virus

Hepatitis C virus (HCV) infection is most often clinically inapparent and rarely associated with symptoms of acute hepatitis. Most patients, however, fail to resolve the acute infection and proceed to develop chronic hepatitis with the risk of liver cirrhosis and hepatocellular carcinoma later in life. Since the kinetics of the earliest events of virus–host interaction are likely to determine the outcome of infection, research has focused on the characterization of the strength and kinetics of the antiviral immune response in different stages of disease. The identification of the immunological correlates of viral clearance is pivotal for the development of vaccines and efficient therapies.     

Human tumor-derived genomic DNA transduced into a recipient cell induces tumor-specific immune responses ex vivo

This article describes a DNA-based vaccination strategy evaluated ex vivo with human cells. The vaccine was prepared by transferring tumor-derived genomic DNA to PCI-13 cells, a highly immunogenic tumor cell line ("recipient cell"), which had been genetically modified to secrete IL-2 (PCI-13/IL-2). PCI-13 cells expressed class I MHC determinants (HLA-A2) shared with the tumor from which the DNA was obtained as well as allogeneic determinants. DNA from a gp100(+) melanoma cell line was transduced into gp100(-) PCI-13/IL-2 cells (PCI-13/IL-2/DNA). A T cell line specific for the gp100 epitope responded to PCI-13/IL-2/DNA cells by IFN-gamma-secretion measured in enzyme-linked immunospot assays. The T cell line also recognized the gp100 epitope presented by dendritic cells that ingested PCI-13/IL-2/DNA cells, which had been induced by UVB irradiation to undergo apoptosis. After up-take and processing of apoptotic PCI-13/IL-2/DNA cells, the dendritic cells primed normal peripheral blood lymphocytes to generate effector T cells specific for the tumor donating the DNA. The results indicate that tumor epitopes encoded in such DNA are expressed in recipient cells and can induce tumor-specific T cells. The findings support translation of this vaccination strategy to a phase I trial in patients with cancer.     

Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against group A streptococcus

BACKGROUND: The development of a vaccine to prevent infection with group A streptococcus (GAS) is hampered by the widespread diversity of circulating GAS strains and M protein types, and it is widely believed that a multivalent vaccine would provide better protective immunity. METHODS: We investigated the efficacy of incorporating 3 M protein serotypic amino-terminal epitopes from GAS isolates that are common in Australian Aboriginal communities and a conformational epitope from the conserved carboxy-terminal C-repeat region into a single synthetic lipid core peptide (LCP) vaccine construct in inducing broadly protective immune responses against GAS after parenteral delivery to mice. RESULTS: Immunization with the tetraepitopic LCP vaccine construct led to high titers of systemic, antigen-specific IgG responses and the induction of broadly protective immune responses, as was demonstrated by the ability of immune serum to opsonize multiple GAS strains. Systemic challenge of mice with a lethal dose of GAS given 60 or 300 days after primary immunization showed that, compared with the control mice, the vaccinated mice were significantly protected against GAS infection, demonstrating that the vaccination stimulated long-lasting protective immunity. CONCLUSIONS: These data support the efficacy of the LCP vaccine delivery system in the development of a synthetic, multiepitopic vaccine for the prevention of GAS infection.     

Human immune responses to a novel norwalk virus vaccine delivered in transgenic potatoes

A new approach for delivering vaccine antigens is the use of inexpensive, plentiful, plant-based oral vaccines. Norwalk virus capsid protein (NVCP), assembled into virus-like particles, was used as a test antigen, to determine whether immune responses could be generated in volunteers who ingested transgenic potatoes. Twenty-four healthy adult volunteers received 2 or 3 doses of transgenic potato (n=20) or 3 doses of wild-type potato (n=4). Each dose consisted of 150 g of raw, peeled, diced potato that contained 215-751 microgram of NVCP. Nineteen (95%) of 20 volunteers who ingested transgenic potatoes developed significant increases in the numbers of specific IgA antibody-secreting cells. Four (20%) of 20 volunteers developed specific serum IgG, and 6 (30%) of 20 volunteers developed specific stool IgA. Overall, 19 of 20 volunteers developed an immune response of some kind, although the level of serum antibody increases was modest.