Helminth functional antigens (with special reference to S. mansoni)

Study of helminth antigens with a special reference to Schistosoma are reviewed, not exhaustively but rather as an overview of trends. These antigens are considered at four levels. Firstly, characterization and utilization of genus, species or stage-specific antigens should improve the efficiency of immunological diagnosis of helminth diseases. Then, some well-characterized antigens are of interest because of their involvement in the modulation of the immune response or in the immunopathological field. Finally, identification of relevant antigens capable of eliciting a protective immune response is a prerequisite to any attempt at immunoprophylaxy of helminthic infections.     

Serum protein polymorphism in Bali (Indonesia)

Serum samples from Bali, obtained in three different ethnic groups and in one isolated village were tested by isoelectric focusing electrophoresis for Gc, Pi, Tf and Hp subtyping. In addition to the three common alleles Gc1F, Gc1S and Gc2, two variants Gc1A1 and Gc1A8 were observed. In the Pi system, five alleles were present: PiM1, PiM2, PiM3, PiM4 and PiX. The Tf variability was exceptional with the presence of eight alleles: TfB1, TfC1, TfC2, TfC3, TfC4, TfC8, TfD1 and TfDchi. For Hp, there were two common alleles Hp1S and Hp1FS and two rare ones: Hp1F and Hp2SS. As expected, the genetic polymorphism is reduced in the isolated community. The anthropological significance of these genetic data is discussed.     

Failure to detect association of isolated cleft palate with HLA antigens

HLA antigen frequencies have been determined in 282 controls and in 33 individuals with isolated cleft palate or the related birth defect velopharyngeal incompetence. No association of particular HLA antigens with this birth defect was found. A previously reported association of HLA A2 with cleft palate, in males, was not confirmed.     

Studies of mycobacterial antigens, with special reference to Mycobacterium leprae.

Eight individual antigens were detected in soluble antigen preparations from Mycobacterium leprae bacilli by using pools of serum samples from lepromatous leprosy patients as antibody reagents in crossed immunoelectrophoresis. Two of these antigens were analyzed further. Antgent no. 1 gave an elution pattern on Sephadex G-200 corresponding to a molecular weight of 285,000. This antigen was also present in three slow-growing and eight fast-growing mycobacterial species. There was a reaction of complete identity in immunological tests using lepromatous serum pools as well as with rabbit antisera raised against M. leprae and M. smegmatis. Antigen no. 21 of M. leprae showed antigenic heterogeneity when compared with other species. Three types of antigenic determinants were detected; one, called 21A, was shared by all mycobacteria, another, called 21B, was limited to antigen no. 21 of M. leprae; a third, called 21C, was present in all mycobacteria except the leprosy bacillus. This submolecular heterogeneity may indicate a separate taxonomic position of M. leprae among the mycobacteria.     

Reassessment of HLA association with celiac disease in special reference to the DP association

Patients with the late-onset form of celiac disease have been studied for HLA association by conventional serology (DR and DQ typing) and by oligonucleotide probing with gene amplification (DP typing). Patients and controls were sampled in the Bologna area of northern Italy. Almost all patients were positive for DQw2 (94%), being DR3 positive (72%) and/or DR7 positive (65%). The proportion of DR3/7 heterozygotes in the patients was significantly increased over that expected from the Hardy-Weinberg equilibrium. No positive association with DR5 and no significant increase of DR5/7 heterozygotes were observed. Among the DP alleles reported to exhibit an association with celiac disease in other populations, only DPB3 showed a moderate increase of a borderline significance, not attributable to a linkage disequilibrium with DQw2.     

Studies on catalase in ageing Zaprionus paravittiger (Diptera) with special reference to an antioxidant feeding

Zaprionus paravittiger fed with an antioxidant (sodium hypophosphite, 1 X 10(3) microM) supplemented diet exhibited adaptive compensatory responses in catalase activity (quantitative as well as qualitative). The longevity and catalase activity were found to be positively linked. The study denotes that free radical formation and antioxygenic defenses are closely associated and are the possible determinants of life span and ageing.     

Identification of human lymphocyte antigens (HLA) in a semen stain

A method developed for the determination of HLA-A and HLA-B antigens in blood stains has been applied for the identification of HLA antigens in a semen stain, on the basis of the inhibition of the lymphocytotoxic activity of HLA-A and HLA-B antigens of semen stains.     

Analysis of soluble antigens in guinea-pig epidermis: I. An immunoelectrophoretic study with special reference to tissue-specific antigens and enzyme antigens

Soluble antigens of guinea-pig epidermis were analysed by immunoelectrophoresis using rabbit anti-epidermis, anti-gastric mucosa, anti-kidney and anti-brain sera. Fifteen antigens of non-serum origin were detected, one of which was an acid phosphatase. Histochemical staining excluded the possibility of the other antigens being one of the several enzymes tested. To simplify the comparison of immunoelectrophoretic patterns, an effect was made to standardize electrophoretic mobility, using guinea-pig lactic dehydrogenaze isoenzymes as markers. Comparison with thirteen other tissue antigens and an absorption experiment revealed that of the fifteen epidermal antigens, two were widely distributed and thus common antigens, four were specific to epidermis and the remainder were shared by some of the other tissues.     

Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA

Recent publications have shown that certain human leukocyte antigen (HLA) alleles are strongly associated with hypersensitivity to particular drugs. As HLA molecules are a critical element in T‐cell stimulation, it is no surprise that particular HLA alleles have a direct functional role in the pathogenesis of drug hypersensitivity. In this context, a direct interaction of the relevant drug with HLA molecules as described by the p‐i concept appears to be more relevant than presentation of hapten‐modified peptides. In some HLA‐associated drug hypersensitivity reactions, the presence of a risk allele is a necessary but incomplete factor for disease development. In carbamazepine and HLA‐B*15:02, certain T‐cell receptor (TCR) repertoires are required for immune activation. This additional requirement may be one of the ‘missing links’ in explaining why most individuals carrying this allele can tolerate the drug. In contrast, abacavir generates polyclonal T‐cell response by interacting specifically with HLA‐B*57:01 molecules. T cell stimulation may be due to presentation of abacavir or of altered peptides. While the presence of HLA‐B*58:01 allele substantially increases the risk of allopurinol hypersensitivity, it is not an absolute requirement, suggesting that other factors also play an important role. In summary, drug hypersensitivity is the end result of a drug interaction with certain HLA molecules and TCRs, the sum of which determines whether the ensuing immune response is going to be harmful or not.     

HLA antigens in adults negative for antibody to Epstein-Barr virus (EBV)

Evidence for a genetic component in susceptibility to Epstein-Barr virus (EBV) infection was sought by comparing HLA A and B phenotypes of EBV antibody-negative Scottish medical students and randomly chosen antibody-positive controls. No statistically significant differences were observed, but three antigens, (A10, A29 and B15), were relatively underrepresented in the EBV seronegative group; findings which agree with data previously reported from a similar study in Los Angeles. A strong association between the HLA A1/Blank phenotype and EBV seronegativity, evident in the Los Angeles population, was not confirmed in the present study.     

Association of HLA antigens with chronic active hepatitis (CAH) in children

HLA-A and -B antigen frequencies were investigated in a group of 46 children with chronic active hepatitis (CAH) and in a control group of 100 healthy children. The diseased group comprised 43 HBsAg positive and 3 HBsAg negative children. From the antigen frequencies relative risks (RR) were calculated according to the method of Woolf. The A1 and B8 antigens, known to be associated with autoimmune diseases, were only moderately more frequent in the CAH group than in the control. The relative risk for B8 antigen was 2.23 which is near to a significance level of p = 0.05. When the calculations were performed for 43 HBsAg positive CAH children the RR decreased to 1.70. Additionally, observations were performed on associations of HLA antigens with the occurrence of antinuclear antibodies (ANA) and anti-smooth muscle antibodies (SMA). Positive associations were found for ANA with B13 antigen (RR = 14.13) and for SMA with B5 antigen (RR = 13.66) with X2 4.85, and 5.51 respectively, at 1 degree of freedom. The p values, situated between 0.05 and 0.01 were insignificant after the correction for the number of antigens studied.     

Study of HLA antigens in a population of Mali (West Africa)

Eighty-two healthy individuals have been typed for HLA-A, B, C, antigens, and 49 of them also for HLA DR alleles. They were a sample representative of 11 of the 14 Malian ethnic groups living in the area of Bamako (Mali). Phenotypic frequencies have been compared to those of other Negroid and Caucasoid reference populations. As expected, in Negroids the increased frequency of HLA A23, A28, A30, and ATh was confirmed in the present series. Additionally, a significantly increased frequency of HLA B5 (B51 and Bw52) was noted--already observed in some but not all Negroid populations. Conversely, a decreased frequency--compared with that usually found in Negroid population--was observed for the alleles Bw42, Bw58, Cw6, and DRw6. Our results underline the originality of the Malian population among Western Africans.     

Some histological and metabolic properties of an isolated perfused rat brain preparation with special reference to monoamine metabolism

A method is described for perfusing the rat head which results in perfusion of the brain, its covering and the bony skull only. Dye and latex injection studies showed that there was no perfusion of extracranial tissue and thus it was not necessary to remove the lower jaw and facial tissues as described by previous authors. Perfusion with fluorescein demonstrated that the whole brain was perfused. Light microscopy after two hours of perfusion revealed no deterioration in brain-structure. Electron microscopy showed a small increase in the extracellular space and the perivascular space with good preservation of subcellular organelles. Glucose and acetoacetate removal were very similar to those reported for the adult rat in vivo as measured by arterio-venous differences. The concentrations of 5-hydroxytryptamine, dopamine and noradrenaline are maintained at values close to those in vivo during a 2-hr perfusion with a basal medium and the preparation will maintain linear rates of 5-hydroxytryptamine synthesis for 2 h when the medium contains L-tryptophan and tranylcypromine, at rates similar to those measured in vivo. The rate of uptake of L-tryptophan into the brain is similar to that reported after L-tryptophan loading in vivo. The histological and metabolic properties of the preparation are close to those observed in vivo. The method could provide a way in which monoamine metabolism in particular could be studied using an experimental model closer in its properties to the in vivo situation than tissue preparations such as slices or homogenates.     

Histocompatibility (HLA) antigens and diabetic microangiopathy.

To gain further insight into the genetic determinants of diabetic small vessel disease, we studied 22 HLA antigens in 110 juvenile-onset, insulin-dependent diabetics with terminal glomerulosclerosis and retinopathy, who were being prepared for kidney transplant. HLA antigens were comtemporarily determined in non-diabetic kidney transplant recipients and healthy controls. The frequency of antigens A1 and B8 were significantly higher in diabetics than in controls (P less than .02 and .011), but the frequency of BW15 was normal. The data are compatible with the concept that juvenile diabetes with microangiopathy is one of the HLA-B8 associated disorders.