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Biomedical subjects

D Gray

Publications and source records attributed to D Gray.

At least 217 records · Page 12Linked to original sources
PubMed1986

Virgin B cell recruitment and the lifespan of memory clones during antibody responses to 2,4-dinitrophenyl-hemocyanin.

The extent to which B cells newly formed in the bone marrow contribute to primary and secondary B cell responses was investigated. This was assessed by constructing chimeras between congenic strains of rats differing in their kappa light chain allotype. Recipient animals received 800 cGy whole body irradiation with hind limb shielding to protect a proportion of their hemopoietic capacity. These rats then received 3 X 10(8) kappa allotype-marked thoracic duct lymphocytes from donors previously immunized twice with either dinitrophenylated spider crab (Maia squinada) hemocyanin (DNP-MSH) or MSH alone. The chimeras were immunized with DNP-MSH and the production of anti-DNP antibody of both donor and host origin was measured. In the period immediately after immunization both newly formed host virgin B cells and donor memory B cells gave rise to substantial proportions of the anti-DNP antibody. After this initial period, antibody production became sustained by activation of memory B cells only. The chimeras were reimmunized with DNP-MSH at 32 days after their first immunization. There was again evidence of a brief period of both virgin and memory B cell activation followed by memory B cell activation only. Donor B cell clones remained dominant in the established response throughout the 5 months each chimera was studied. The data are interpreted as indicating two phases of B cell activation. It is suggested that the first phase where both virgin and memory B cells are activated may be associated with antigen presentation on dendritic or interdigitating cells outside follicles. It is argued that the second phase where only memory B cells are activated is more likely to be associated with antigen on follicular dendritic cells.

Animals↗
PubMed1986

Differences in the recruitment of virgin B cells into antibody responses to thymus-dependent and thymus-independent type-2 antigens.

The bone marrow of mammals generate large numbers of B cells throughout life. Most of these have a short life span. The subject of this report is to investigate the extent to which newly formed virgin B cells can be activated by thymus-dependent (TD) and thymus-independent type 2 (TI-2) antigens carrying the hapten 2,4-dinitrophenyl. The experimental approach used chimeras made between congenic rats of different kappa immunoglobulin light chain allotype. Host (kappa la) rats were depleted of peripheral B cells by whole body irradiation but had B lymphopoietic capacity conserved by shielding the hind limbs. Their peripheral B cell pool was reconstituted by transfer of kappa lb thoracic duct lymphocytes from donors immunized previously with the TD carrier. This provides test animals where newly produced virgin B cells only express kappa la but where initially most peripheral B cells are kappa lb. The TD antigen tested was able to activated both virgin and memory B cells in the period immediately following immunization. However, long-term antibody production was attributable to repeated activation of memory B cell clones without further virgin B cell recruitment. By contrast, antibody evoked by the TI-2 antigen initially was almost exclusively due to activation of donor peripheral B cells. However, over a period following TI-2 immunization there was a progressive increase in the amount of host antibody produced with corresponding decline of the donor component of the response so that the host response was dominant by six weeks. Control experiments were conducted to show that these effects could not be explained by allotype or isotype-directed suppression. The cellular basis of these differences was investigated further by studying the rate of repopulation of different B cell compartments in these chimeras by newly formed host and mature donor B cells. The results indicate that the onset of host antibody production to the TI-2 antigen closely correlated with the appearance of host B cells in the marginal zones of the spleen, whereas good TD host anti-2,4-dinitrophenyl responses antedated the appearance of host B cells in this compartment. These results are discussed in relation to other data implicating marginal zone B cells in responses to TI-2 antigens.

Animals↗
PubMed1986

Antigen-driven selection of virgin and memory B cells.

This review has summarized the evidence indicating that far more B cells are produced in adult bone marrow than are required to maintain B cell numbers in the periphery. It is shown that most if not all these newly-formed B cells have the potential to become mature peripheral B cells. However, to do this they need to receive an appropriate signal in secondary lymphoid organs. Cells failing to receive such a signal die after a brief period. Two separate situations have been identified which result in recruitment of newly-formed virgin B cells into the peripheral B-cell pool: Following activation by antigen. When the peripheral B-cell pool has been depleted. It is proposed that the first of these signals requires T help and is initiated by antigen presented on interdigitating cells in extrafollicular areas of secondary lymphoid organs. This process seems to be confined to periods immediately following administration of antigen and does not continue in established immune responses to thymus-dependent antigens. It seems probable that continued B cell activation, occurring during long term antibody responses, takes place in the follicles of secondary lymphoid organs and is driven by antigen presented on follicular dendritic cells. Indirect evidence is cited which suggests that somatic mutation in rearranged immunoglobulin V-region genes occurs mainly following B-cell activation in follicles and not during primary B lymphopoiesis. It is suggested that this may involve a hypermutation process which is switched on in activated B cells in germinal centers. Evidence is presented suggesting that plasma cells generated from B cells activated early in immune responses have an average life-span of less than 3 d. However, plasma cells generated in established responses appear to have an average life-span in excess of 20 d. Later sections in the review consider how B-cell recruitment in thymus-independent antibody responses differs markedly from recruitment during thymus-dependent responses. The possible role of splenic marginal zone B cells in some thymus-independent antibody responses is discussed and the evidence indicating that SIgM + ve, IgD-ve marginal zone B cells develop as a distinct population from recirculating SIgM + ve, IgD + ve B cells is summarized.

Adult↗
PubMed1986

Effect of dietary supplements on acute mountain sickness.

Four fit young men participating in a high altitude mountaineering expedition took part in a 15-day trial of two high-calorie dietary supplements. They ate either a high carbohydrate or a high fat supplement, alternating every 3 days. All dietary intake was recorded. Subjects completed a daily questionnaire assessing the severity of symptoms. Within a single-subject design no statistically significant differences were obtained between the severity of symptoms and dietary carbohydrate or total calories. This suggested that the dietary supplements had no effect on symptoms, a finding that is discrepant with the existing literature. However, we did find that subjects consumed more calories while on the high carbohydrate supplement.

Adult↗
PubMed1986

Human immune responses in vivo to protein (KLH) and polysaccharide (DNP-Ficoll) neoantigens: normal subjects compared with bone marrow transplant patients on cyclosporine.

Thymus-independent (TI) and thymus-dependent (TD) primary immune responses were measured in 67 controls and 13 bone marrow transplant (BMT) recipients treated with cyclosporine (CSP) by immunizing with a synthetic antigen (DNP-Ficoll) and keyhole limpet haemocyanin (KLH). DNP-Ficoll induced similar TI antibody responses in controls and BMT recipients except that antibody levels declined much more rapidly in BMT recipients. The IgM and IgG antibodies induced by DNP-Ficoll only recognized the DNP epitope and not the Ficoll carrier. Both IgM and IgG classes of antibody showed similar TI behaviour upon immunization and re-immunization. The antibodies to DNP-Ficoll were overwhelmingly of the IgG1 subclass. The TD response to KLH evoked both delayed hypersensitivity (DH) and antibody production. DH developed at the site of immunization in 68% of controls and in 88% upon subsequent challenge with KLH. None of the BMT recipients on CSP developed DH. KLH antibody arose in 88% of controls but in only one BMT recipient on CSP. Eight BMT recipients were re-immunized with KLH 2-6 weeks after stopping CSP and only one made primary DH and antibody responses, arguing that CSP inhibited priming as well as any detectable response to KLH. The immunization procedure described has proved a sensitive and comprehensive method of quantitating human immune responses in vivo and is readily adaptable for in vitro studies.

Adolescent↗
PubMed1986

Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas.

Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes.

Cells, Cultured↗
PubMed1985

Enalapril maleate and atenolol combined with hydrochlorothiazide in moderate to severe essential hypertension.

This open randomised parallel trial compared the antihypertensive efficacy of enalapril and atenolol given alone once a day or with hydrochlorothiazide in 20 patients with moderate to severe hypertension. Active treatment was over a 26 week period, consisting of an initial titration phase followed by a fixed dose phase. Both treatment regimes effectively lowered systolic and diastolic blood pressures. All patients on enalapril reached normotension (supine diastolic blood pressure less than or equal to 90 mmHg) compared with 78% on atenolol. Pulse rate was not appreciably changed by enalapril, but was significantly reduced by atenolol. No serious adverse reactions or significant changes in laboratory values were noted in either group. The commonest adverse reaction with enalapril was dizziness which occurred in two cases and resolved on dosage reduction. Enalapril with hydrochlorothiazide given once daily may provide a useful combination in the treatment of moderate to severe hypertension.

Adult↗
PubMed1985

The treatment strategies of arthritis sufferers.

This paper describes and analyses the reasons for variation in the treatment strategies used by arthritis sufferers. The research was undertaken among 103 people from the Australian city of Perth. Qualitative data was obtained from a clinical sample of 27 and, on the basis of that, an interview schedule was constructed and administered to a survey sample of 76 self-reported arthritis sufferers. Data collected included comprehensive case histories, knowledge and beliefs about arthritis, types of practitioners consulted and treatments used and a range of demographic and socioeconomic variables. On the basis of analysis, four basic treatment strategies were discerned. Named after their most salient characteristics and ranging from least to most inclusive these were 'general practitioner and/or self care', 'medical and paramedical care', 'medical and alternative care' and use of 'all sources of care'. The most important determinants of treatment strategy were characteristics of disease--severity, mode of onset and period since onset. The longer the period since onset, the wider the range of treatments utilized. When onset occurred at a relatively young age and when progression was rapid, the more frequently alternative services and treatments were employed. Disease characteristics were followed in importance by socioeconomic factors. Use of the less inclusive strategies was related to social class; with working class people relying primarily on 'general practitioner and/or self care' and middle class people using 'medical and paramedical care'. However, when onset and progression were rapid, the disease was severe and the person relatively young socioeconomic factors were of lesser importance and people from all classes made use of the more inclusive strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis↗
PubMed1985

Selective depression of thymus-independent anti-DNP antibody responses induced by adult but not neonatal splenectomy.

The effect of splenectomy was assessed on rats' capacity to respond to 2,4-dinitrophenol (DNP) conjugated to spider crab haemocyanin (MSH) or hydroxyethyl starch (HES). The response to DNP-HES was profoundly suppressed in all immunoglobulin classes and subclasses by adult splenectomy. This loss of responsiveness increased with time after removal of the spleen. By contrast no significant effect on the anti-DNP-MSH response was caused by splenectomy. Experiments in congenitally athymic rats confirmed the thymus dependency of anti-DNP antibody responses of all classes and subclasses induced by DNP-MSH. DNP-HES responses, however, were elevated in athymic animals. The effect of adult splenectomy in these animals was considerably less than that produced in euthymic rats. Neonatal splenectomy in euthymic rats only resulted in minor impairment of these rats' capacity to respond to DNP-HES as adults, indicating the ability of rats to compensate after neonatal but not adult splenectomy. These data are taken to show that the spleen plays an important role in responses against this thymus-independent type II antigen which is only partially replaceable by other compartments of the immune system.

2,4-Dinitrophenol↗
PubMed1985

Class and subclass anti-pneumococcal antibody responses in splenectomized patients.

Antibody titres against pneumococcal capsular and cell wall antigens and the immune response to polyvalent pneumococcal vaccine were measured in 21 splenectomized patients and 12 healthy controls. Most individuals possessed anti-pneumococcal capsular polysaccharide antibodies of IgG, IgA and IgM classes. The anti-capsular IgG was predominantly of the IgG1 and IgG2 subclasses; only occasional individuals had any detectable titre in IgG3 or IgG4 subclass. Most individuals responded to immunization with Pneumovax. There was no clear difference between groups of control and splenectomized subjects, although three of the splenectomized patients had undetectable pre-immunization anti-capsular titres in one or more subclass which failed to rise following immunization. All subjects tested had anti-phosphocholine antibodies in IgG, IgA and IgM classes with the exception of a single splenectomized patient who lacked detectable anti-phosphocholine IgM. Pre-immunization titres where similar in healthy controls and splenectomized patients. There was no demonstrable rise in anti-phosphocholine titre following immunization with Pneumovax.

Adult↗
PubMed1984

Marginal zone B cells express CR1 and CR2 receptors.

Opsonized yeast is known to bind strongly to the marginal zones in frozen sections of rat spleen (Kumararatne, D. S. et al., Eur. J. Immunol. 1981. 11: 858). This study reports an analysis of the cells involved in this binding. Sheep red cells coated respectively with C3b, C3bi or C3d were used as indicator cells. These showed homogeneous binding of both C3b and C3bi to marginal zones and germinal centers. C3d-coated red cells bound in a uniform speckled pattern to marginal zones. They also bound to germinal centers and the small lymphocyte zones of the follicles. Selective depletion experiments were undertaken to show that binding to marginal zones was a property of the IgM+ and IgD- B cells characteristic of this area. Binding to germinal centers was attributable to follicular dendritic cells. The C3d receptors in follicles were shown to be on IgM+ and IgD+ small B lymphocytes.

Animals↗