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Biomedical subjects

G L Ada

Publications and source records attributed to G L Ada.

At least 19 recordsLinked to original sources
PubMed1997

DNA immunization.

DNA immunization has recently emerged as a highly promising approach for the prevention and therapy of a wide range of infectious and non-infectious diseases. Here, we review the rapid development of this field and recent advances in our understanding of some of the mechanisms by which DNA vaccines stimulate the immune system.

Animals↗
PubMed1994

Human vaccines.

With very few exceptions the vaccines available for general medical use are to control relatively acute viral or bacterial infections. The vaccines are either live attenuated, inactivated whole organisms or subunit preparations. Developing live attenuated viral vaccines has been and continues to be a popular approach, because generally, they give long-lasting immunity after one or two administrations. Until recently this has been a less successful approach for bacterial vaccines, but the prospects are now brighter. Subunit preparations (oligosaccharides) of encapsulated bacteria as hapten:carrier conjugates also show considerable promise. The demonstration that a viral antigen, the surface antigen of hepatitis B virus, could be produced by genetic-engineering, opened the way to the development of chimeric live vectors.

Adult↗
PubMed1993

Affinity maturation of lymphocyte receptors and positive selection of T cells in the thymus.

In this review we have re-evaluated the dominant paradigm that TcR V genes do not somatically mutate. We highlight the many structural and functional similarities between Ig and TcR antigen-specific receptors on B and T cells. We have reviewed the factors influencing the somatic and germline evolution of IgV regions in B cells, have evaluated in detail various models which could be invoked to explain the pattern of variation in both transcribed and non-transcribed segments of germline IgV-gene DNA sequences, and applied this perspective to the TcR V beta and V alpha genes. Whilst specific TcRs recognize a complex of a short antigenic peptide bound to MHC Class I or II glycoprotein, and Ig receptors can recognize both oligopeptides and conformational determinants on undegraded polypeptides, they both employ heterodimer variable regions (Fabs) utilizing all three CDRs in epitope binding. We conclude that a plausible case can be made for the possibility that rearranged TcR V genes may undergo some type of somatic hypermutation process during T-cell development in the thymus (concurrent with or after the positive selection phase) thus allowing a repertoire of TvR alpha beta heterodimers to be both positively and negatively selected by the same set of ligands (self MHC + self peptide) in the thymus.

Animals↗
PubMed1989

Antibody-mediated enhancement of hormone activity.

The enhancement of hormone activity by antibodies has been known for many years; however, investigation into the molecular basis of the phenomenon has only recently begun. A number of mechanisms for this enhancement, including "buffering" or slow release, bivalency and Fc region, and conformational and receptor "restriction" effects, have been documented or proposed. The availability of panels of monoclonal antibodies of distinct combining site specificity have aided in these studies and contributed substantially to our understanding of hormone-receptor interactions.

Animals↗
PubMed1988

The initiation and early development of autoimmune diseases.

Our understanding of autoimmunity has changed considerably over the past years as a consequence of the demonstration that self-reactive B cells and T cells are not necessarily deleted from the immunological vocabulary. The critical event in initiating (or avoiding) autoimmune responses is presentation to T cells of the self-peptide-MHC antigen complex. Based on the premise that quantitative aspects are of paramount importance, we suggest that T-cell activity, MHC expression, and self-peptide binding determine the initiation of autoimmune responses.

Animals↗
PubMed1988

What to expect of a good vaccine and how to achieve it.

Vaccines have been used almost exclusively to prevent or control infectious diseases with the aim of long-lasting immunity. Some, composed of attenuated viruses, have been highly successful and this may be due to the generation of high levels of B memory cells and their steady recruitment to form antibody secreting cells. Some diseases, notably AIDS, are a much greater challenge and it will need all the expertise of molecular biologists and immunologists to devise a vaccine which may control the disease. Vaccination to enhance or decrease the action of hormones is now being actively explored as a practical way of controlling fertility in mammals or enhancing selected properties of other hormones. In this situation, the desired effect is for a defined period, possibly one year or less. These requirements underline further the need for controlled release formulations for vaccine delivery.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses.

A-strain influenza virus A/JAP (H2N2) was tested for its ability to induce cytotoxic T cells (Tc) after being rendered non-infectious by either UV or gamma irradiation. Gamma-irradiated virus proved to be more efficient than UV-inactivated virus in priming for a memory Tc cell response or in boosting memory spleen cells in vitro. Most importantly, gamma-inactivated, but not UV-inactivated, A/JAP immunized animals survived lethal challenge with heterologous (A/PC(H3N2), A/WSN(H1N1)) virus as effectively as mice primed with infectious virus.

Animals↗
PubMed1988

Cellular immune responses in the murine lung to local immunization with influenza A virus glycoproteins in micelles and immunostimulatory complexes (iscoms).

Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.

Animals↗
PubMed1988

Modern approaches to vaccine development with special reference to the needs of developing countries.

Vaccination has proved to be one of the most effective public health measures to control infectious diseases. The eradication of smallpox by world-wide vaccination represents one of mankind's greatest achievements. Despite the availability of vaccines to control many diseases, they are generally under-used in many developing and some developed countries. However, there are many diseases for which current vaccines are inadequate or vaccines cannot be prepared using conventional approaches. This article describes the new approaches which are now available and are being used extensively to develop new vaccines against viral, bacterial and parasitic diseases. Success has already been achieved in a few cases and the prospect for others is encouraging. In addition, progress is being made to develop vaccines to control human fertility as this development is seen to complement the control of infectious diseases.

Developing Countries↗
PubMed1988

Prospects for HIV vaccines.

This article initially discusses the types of responses elicited by infectious agents, such as viruses and the role of each response in preventing, limiting, and clearing the infection. An important response is the generation of immunological memory, in both the B and T cell compartments. Generally, attenuated viral vaccines have been highly successful at inducing long-lived immunity but our understanding of the reasons for this comes from the study of model systems, such as murine influenza virus infections. Specific antibody may largely prevent infection and specific cytotoxic T cells and antibody-dependent cell cytotoxic reactions are the main mechanisms for clearing viral infections. Recent evidence shows that for some months after infection by HIV, a strong cytotoxic T (Tc) cell response occurs in infected, asymptomatic individuals; these cells are continuously generated by HIV-infected stimulator cells that most likely also serve as target cells in vivo. A low level of specific antibody is also formed and a number of reasons are listed to explain why HIV escapes antibody-mediated neutralization and infects cells expressing CD4 receptors. Cells of the macrophage/monocyte lineage are also infected and these express Fc and complement receptors; there is the strong possibility that infection of these cells occurred following the formation of complexes of infectious HIV with antibody to the surface antigen and attachment of complement components. The continuous presence of activated Tc cells that, in contrast to many other viral diseases, does not clear the infection strongly suggests that foci of infected cells sequestered from or resistant to immune control become established. These secrete virus that infects other (stimulator) cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗