The immune response to a synthetic amino acid terpolymer in man: relationship to HL-A type.

The immune response to the synthetic amino acid terpolymer (L-glutamic acid-55 L-lysine-33 L-tyrosine15)n (GLT) was studied in normal human volunteers. Delayed skin test reactivity to this antigen was seen in 34 of 61 subjects immunized with 150 mug of GLT. No antibody to GLT was detected in these responding individuals. There was a close correlation between the in vivo skin reactivity of volunteers to GLT and the ability of their lymphocytes to produce migration inhibitory factor (MIF) in response to GLT in vitro. However, a similar correlation was not seen when the in vitro proliferative response of lymphocytes to GLT, as measured by [methyl-3H] thymidine ([3H] T dR) incorporation, was assayed. HL-A typing of volunteers was studied to determine if responsiveness to GLT was correlated to HL-A type. No statistical association was seen after correction was made for the number of individual HL-A antigens.     

The high background immune reactivity of mice to polymorphic determinants on xenogeneic erythrocytes: theoretical and practical implications

Background responses have been assessed by fusing lipopolysaccharide- (LPS) stimulated spleen cells from unimmunized mice with MOPC 315.43 myeloma cells and screening the hybrids for the production of antibody against chicken red blood cells (CRBC). Clones specific for CRBC represented about 1% of total hybrid clones (1000 to 5000 clones were obtained per mouse). The majority of the anti-CRBC clones (greater than 95%) secreted antibody against polymorphic CRBC determinants (present on CRBC from some but not all chickens) rather than species-specific determinants present on all CRBC. Some of the polymorphic determinants were linked to the B locus (the MHC of the chicken) and some were non-B antigens. The relative amount of these 2 categories varied slightly according to the mouse strain. These results agree well with the specificities of natural mouse antibody and rosette-forming spleen cells. The response of immunized mice against CRBC and human RBC was also selective for polymorphic determinants. These results have considerable importance for the use of xenogeneic RBC as "standard" antigens, and are interpreted in terms of a model for the advantages of genetic polymorphism as a protection against antigen mimicry by parasites.     

Genomic instability, bystander effects and radiation risks: implications for development of protection strategies for man and the environment

The last few years has seen what people are now referring to as a "shifting Paradigm" in our way of thinking about radiation effects on biological systems. The concept of the central role of DNA damage due to double strand breaks induced by a radiation "hit" has been itself hit by many studies showing persistent effects in the distant progeny of radiation exposed cells. This phenomenon is known as radiation induced genomic instability. More recently evidence has been accumulating that not even the parent cell need be exposed to radiation (the bystander effect). The new paradigm suggests that cellular stress responses or damage signalling through a range of signal transduction pathways are involved and that cell-cell contact or secretion of damage signalling molecules can induce responses in undamaged and unirradiated cells. Are these new effects relevant to risk assessment, or does it matter HOW radiation affects cells if we have good epidemiological evidence of which to base our risk estimates? The aim of this paper is to introduce the new concepts and to consider reasons why they might alter our methods of risk estimation. The paper also considers the impact of the new concepts on environmental protection and discusses the need for research in the field of comparative radiobiology if we are to develop policies which can adequately protect biodiversity.     

Stress-induced immune dysfunction: implications for health

Folk wisdom has long suggested that stressful events take a toll on health. The field of psychoneuroimmunology (PNI) is now providing key mechanistic evidence about the ways in which stressors--and the negative emotions that they generate--can be translated into physiological changes. PNI researchers have used animal and human models to learn how the immune system communicates bidirectionally with the central nervous and endocrine systems and how these interactions impact on health.     

Radiation-induced lysosomal iron reactivity: implications for radioprotective therapy

A novel mechanism of radiosensitization involves radiation-enhanced autophagy of damaged mitochondria and various metalloproteins, by which iron accumulates within lysosomes. Hydrogen peroxide, formed by the radiolytic cleavage of water, generates in the presence of lysosomal redox-active iron extremely reactive hydroxyl radicals by Fenton-type chemistry. Subsequent peroxidative damage of lysosomal membranes initiates release of harmful content from ruptured lysosomes that triggers a cascade of events eventuating in DNA damage and apoptotic or necrotic cell death. This article reviews the role of lysosomal destabilization in radiation-induced cell damage and death. The potential effects of iron chelation therapy targeted to the lysosomes for protection of normal tissues against unwanted effects by radiation is also discussed.     

The dynamics of the cellular immune response to HIV infection: implications for vaccination

Recent advances in measuring T-cell responses to viruses have led to new insights into how these T cells respond. In the acute infection there are massive CD8+ T-cell responses to both Epstein-Barr virus (EBV) and to human immunodeficiency virus (HIV). Many of these T cells are effector cells and only a minority appear to be capable of maintaining immunological memory. In persistent virus infections, high levels of antigen-specific effector cells persist. If virus does not persist, the effectors fade in number but memory is maintained and is primed to react rapidly to a new challenge. A vaccine that stimulates only T-cell responses may protect when these memory cells respond rapidly enough to generate high numbers of effectors before the infecting virus becomes established.     

Ability of man to detect increases in his breathing.

The ability of four normal subjects to detect increases in their ventilation was studied at rest and at two levels of exercise using a raised inspired Pco2 to further increase ventilation. Subjects signaled when the increase in ventilation was recognized. The average tidal volume (VT) at rest was 520 ml with a frequency of 14; these values increased to an average of 3,300 ml and 21 at the highest work load. There was no significant change in frequency with CO2. Detection occurred when the tidal volume increased by 700 ml (varying 550-890 between subjects but constant for any one subject at the three levels of ventilation.) Thus the appreciation of increase is proportionately more sensitive at higher levels of ventilation. Experiments in which the ventilation was increased by hypoxia or by following a visual demand, and observations of other sensations (oral, cerebral) indicate that the increase in vetilation is recognized through increased breathing rather than awareness of ventilatory stimuli.