[The future of vaccines: recombinant DNA vaccines]. / De toekomst van vaccins: recombinant-DNA vaccins.

Classical approaches to the development of vaccines have provided mankind with a number of safe and effective vaccines (think of the world-wide eradication of smallpox). Nevertheless, some obstacles e.g. the production of a safe Hepatitis B vaccine, could not be taken by classical techniques. In several cases, recombinant-DNA technology provided an elegant solution, though in other cases, this technique also failed. The present paper presents a brief review of the role of recombinant-DNA technology in the current development of vaccines.

Flurbiprofen and immunosuppression of Trypanosoma brucei infection in the goat.

Goats infected with Trypanosoma brucei and treated with the non-steroidal anti-inflammatory agent flurbiprofen, showed a marked increase in parasitaemia, followed in one of the four goats by death. The in vitro response to mitogens of peripheral blood lymphocytes and separated T- and B-lymphocytes from healthy goats treated with flurbiprofen was normal when compared with non-treated animals. T. brucei-infected goats, not treated with flurbiprofen, showed a marked immunosuppression which was mainly localized in the B-enriched lymphocyte fraction. A combination of T. brucei infection and treatment with flurbiprofen led to even more suppression, because the T-lymphocyte function was also suppressed. It is concluded that flurbiprofen first causes a rise in the parasitaemia and that this high parasitaemia is responsible for the observed immunosuppression.

Presence of antigen sensitized leukocytes in carp (Cyprinus carpio L) following bath immunization against Flexibacter columnaris.

Bath immunization of carp (Cyprinus carpio L) resulted in protection of fish at natural challenge. Stimulation of leukocytes derived from thymus, spleen, anterior kidney and mid-kidney of fish immunized with Flexibacter columnaris bacterin revealed the presence of antigen sensitized cells in all lymphoid tissues except the anterior kidney. After 28 days a response was obtained in thymus and spleen leukocyte cultures.

Optimization and kinetics of in vitro stimulation of carp (Cyprinus carpio L.) leukocytes.

The optimization of a leukocyte stimulation microassay with carp (Cyprinus carpio L.) leukocytes is described. Leukocytes were isolated from the thymus, anterior kidney, spleen, mid-kidney and peripheral blood. Leukocyte cultures were stimulated with PHA-P, LPS (Escherichia coli 055: B5) PWM, ConA and PPD from Mycobacterium fortuitum. The optimum incubation temperature for leukocyte cultures differed 3.5 days for leukocyte cultures derived from lymphoid organs and 4.5 days for peripheral blood lymphocyte cultures. Leukocytes from various organ sources showed similar reactivity patterns to stimulation in vitro by different mitogens. The results of these mitogen stimulations did not present sufficient arguments in favour of compartmentation.

Induction and effector phases of the immune response: physiological and pathophysiological features.

A review is given on the current state of knowledge about the induction and effector phases of the immune response. Physiological and pathophysiological features of the regulation of the immune response are discussed comparatively for both man and animals.

The histocompatibility complex GLA in the goat.

The current status of research on the major histocompatibility complex of the goat (GLA) is discussed, as well as its similarities to other species, although some of the results are preliminary.

Analysis of alloantisera against bovine lymphocytes. Joint report of the 1st International Bovine Lymphocyte Antigen (BoLA) workshop.

The results and agreements of the 1 international BoLA workshop, held in Edinburgh, Scotland in August 1978, are reported. Most of these concern the results from a comparison test of 249 alloantisera to bovine lymphocytes, the antisera being contributed by 9 laboratories. These sera were compared directly in Edinburgh on a panel of lymphocytes from 130 cattle of 21 breeds. In the microlymphocytotoxicity test used 75% of the sera reacted. Sixty eight of these sera were grouped into clusters according to their reaction patterns against the lymphocyte panel. Eleven of these clusters were clearly defined and were given workshop BoLA designations. In addition 22 sera were assigned to subgroups of the agreed clusters. There was no evidence that the method of production of the sera had any effect on their specificity. Although genetic data was not available, the phenotypes of the test panel of lymphocytes are consistent with the clusters detecting antigens controlled by multiple alleles at a single autosomal locus. It was agreed to name the genetic region where this putative locus is located BoLA (bovine lymphocyte antigen).

[Tissue antigens and bacterial infection (author's transl)]. / Weefselantigenen en microbiële infecties.

Rejection of tissue- and organ-grafts is due to the existence of tissue- or transplantation-antigens which are present in principle on every nucleated body-cell. These tissue antigens represent the phenotypical expression of a complex system of genes which are localized on an autosomal chromosome: the histocompatibility system. These systems may usually be compared with bloodgroup systems. Besides the successful use of tissue typing in transplantation, it became apparent that histocompatibility systems may have another function. Among others, tissue typing may be correlated with resistance to and susceptibility to particular diseases. However, it is not clear so far whether tissue antigens play a role themselves or only serve as genetic markers in this regulation of the immune response. The two possibilities are introduced, together with some instances. Finally, on the basis of possible veterinary and economic importance, studies on histocompatibility systems in pets and farm animals are reviewed, a number of possible uses being suggested.

Skin grafting and graft rejection in goats.

As part of a study to define the major histocompatibility complex of the goat and to show certain aspects of its biological function, a skin-grafting technique is described which might also be applicable for similar studies in other ruminant species.

Quantification of turkey immunoglobulins IgA, IgM and IgG in serum and secretions.

The immunoglobulins IgA, IgM and IgG of the turkey were quantitated in individual serum samples as well as in pooled sera. The variability of Ig levels in normal, healthy birds was quite high: IgA: mean value 0.633 mg/ml (4.0 -x - 2.5 -x); IgM: mean value 4.37 mg/ml (0.5 -x - 1.4 -x) and IgG: mean value 8.92 mg/ml (0.6 -x - 1.7 -x). Immunoglobulin levels in egg-yolk, egg-white, bile and some intraocular tissues were quantitated as well. An interesting finding was, that the forementioned variability was by far not so high with respect to IgG levels in 20 egg-yolk samples: mean value 5.1 mg/ml (0.86 x- - 1.17 -x). Though IgG and IgM could be detected in pooled turkey bile, IgA predominated in this secretion. In aqueous humor, iris tissue and vitreous body only IgG could be detected.

Protein A reactivity of various mammalian immunoglobulins.

Serum samples and immunoglobulin fractions of eight mammalian species were applied to a Sepharose--protein A column. As with the human immunoglobulin subclasses IgG1, IgG2 and IgG4, all examined IgG classes and subclasses were bound to a greater or lesser extent to protein A. However, the binding of IgG1 of ruminants was very poor. Polyclonal IgM and IgA of the pig, the dog and the cat may be separated in protein A reactive and protein A non-reactive fractions. In addition, monoclonal canine IgM and IgA partially reacted with protein A. In combination with methods such as ammonium sulphate precipitation, ion exchange chromatography and gel-filtration, affinity chromatography with protein A is recommended for the rapid purification of certain Ig (sub)classes of a number of mammalian species.

Common precursor molecule as origin for the ectopic-hormone-producing-tumour syndrome.

When messenger R.N.A. (m-R.N.A.) extracted from various hormone-secreting tumours was injected into Xenopus eggs, the translation products in all cases proved to be a protein of molecular weight 65 00. Analysis by polyacrylamide-gel electrophoresis and specific precipitation reactions with antibodies showed a striking similarity between the various proteins. When translation products of m-R.N.A. from calcitonin-secreting medullary thyroid carcinoma (M.T.C( and the non-secreting anaplastic form of M.T.C. were incubating with specific enzyme systems (the microsomal fraction) from both types of tumour, enzymes from anaplastic M.T.C. had no effect on the translation products, whereas enzymes from differentiated M.T.C. degraded the translation products from both differentiated and anaplastic M.T.C. The results support the hypothesis that the primary gene product of all the different types of carcinoma cell studied is a single large protein (a hormone precursor or prohormone) containing different specificities. The specific enzyme system in each carcinoma cell probably selects the specific hormone liberated from this primary protein.

In vitro stimulation of goat peripheral blood lymphocytes: optimization and kinetics of the response to mitogens and to allogeneic lymphocytes.

Experiments were performed to establish the optimal concentrations for specific and non-specific lymphocyte transformation in vitro, in cultures containing 10(5)-10(6) caprine lymphocytes. A microculture system was used in conjunction with a semiautomatic sample harvester. The assay was optimized for mitogen concentration (PHA-P, Con A, PWM and LPS) and allogeneic cell number, number of responding cells, incubation time and amount of tracer. The effect of addition of serum and the cytotoxic effect of phytomitogens on cultured cells is discussed.

The immunoglobulins of the turkey (Meleagris gallopavo). Isolation and characterization of IgG, IgM and IgA in body fluids, eggs and intraocular tissues.

The distribution of the immunoglobulins IgG, IgM, and IgA in turkey serum, bile, egg white, egg yolk, intestinal secretions, and some intraocular tissues has been studied. Just as in the chicken and the pigeon, IgG is the most abundant immunoglobulin in the serum and IgA in egg white, intestinal secretions and bile. In addition, IgM was detected in serum and egg white, and IgG in egg yolk, iris, vitreous body, and aqueous humor. The discussion deals with the importance of using purified immunoglobulin fractions and heavy-chain-specific antisera in disease studies in the turkey, specially in the case of infectious diseases which lead to the occurrence of "rheumatoid factors".

Histocompatibility in ruminants. The production and evaluation of allo-antibodies for GL-A typing in goats.

The production of goat lymphocytotoxic allo-antisera by immunization by lymphocytes or allografting is described. Analysis of typing results of several goat families and the correlation between the lengthening of allograft survival and graft exchange between compatible and incompatible animals, suggest the existence of a major histocompatibility system (GL-A) in goats.