New data on the mechanism of action of immuno-adjuvants: Applications in veterinary medicine

Certain natural or synthetic peptidoglycans which act as watersoluble adjuvants represent a new family of drugs which can act selectively on certain lymphoid cells, B or T cells or macrophages. Some of these molecules can inhibit the immune response.We have developed a technique which enables either normal membranous vesicles, (cellular surface on the outside, RSO), or inverted vesicles, (cellular surface on the inside, IO), to be taken from a murine plasmacytoma. Some peptidoglycans act on the RSO vesicles, others on the IO vesicles, in every case by activating and/or inhibiting membranous enzymes such as 5-nucleotidase and Na⁺/K⁺ ATPase.It is likely that the immuno-adjuvants act selectively and that the same substance can activate or inhibit according to the dose used.

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Kurzfassung Bestimmte natürliche oder synthetisch hergestellte Peptidoglykane (wasserlösliche Adjuvanzien) sind eine neue Familie pharmakodynamischer Agenzien, die elektiv auf bestimmte Lymphoidzellen, B-Zellen, T-Zellen oder Makrophagen wirken. Bestimmte Moleküle können die Immunreaktion inhibieren. Es wurde ein Verfahren erarbeitet, mit dem aus einem Plasmozytom bei Ratten oder Mäusen Membranbläschen gewonnen werden konnten, die entweder richtig geformt (Zelloberfläche aussen, RSO) oder umgekehrt (Zelloberfläche innen, IO) sind. Manche Peptidoglykane wirken auf RSO, andere auf IO; in allen Fällen ist diese Wirkung gekennzeichnet durch die Activierung und/oder Inhibierung von Membranenzymen wie der 5-Nukleotidase und der Na+/KA—ATPase.Voraussichtlich haben die Immunitätsadjuvanzien eine Zielspezifität und derselbe Stoff kann je nach Dosierung stimulierend oder inhibierend wirken.Riassunto Gli adiuvanti idrosolubili, che sono peptido-glicani naturali o sintetici, costituiscono una nuova famiglia di agenti farmacodinamici in grado di agire selettivamente su alcune cellule linfoidi, le cellule B, T o macrofagi. Alcune molecole possono inibire la reazione immunitaria.Gli autori hanno messo a punto una tecnica che permette di ottenere, partendo da un plasmocitoma murino, vescicole membranose girate nel senso giusto (superficie cellulare rivolta all-esterno RSO) o rovesciate (superficie cellulare all'interno, IO). Alcuni peptido-glicani sono attivi sulle RSO, altrillo sono sulle IO; in ambedue i casi detta attività è caratterizzata dall-attivazione e/o dall'inibizione di enzimi membranosi come la 5 nucleotidasi e la Na⁺/K⁺ ATP-asi.Si puo ipotizzare che gli adiuvanti dell'immunita posseggano una specificita di bersaglio, e che la medesinna sostanza possa rivelarsi stimolante od inibitoria a seconda della dose impiegata.

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Resume Les adjuvants hydrosolubles que sont certains peptidoglycanes naturels ou synthétiques représentent une nouvelle famille d'agents pharmacodynamiques capables d'agir électivement sur certaines cellules lymphoides, cellules B, T ou macrophages. Certaines molécules peuvent inhiber la réponse immunitaire.Nous avons mis au point une technique permettant d'obtenir à partir d'un plasmocytome murin des vésicules membranaires tournées dans le bon sens (surface cellulaire à l'extérieur, RSO) ou inversées (surface cellulaire à l'intérieur, IO). Certains peptidoglycanes sont actifs sur les RSO, d'autres sur les IO: dans tous les cas cette activité est caractérisée par l'activation et/ou l'inhibition d'enzymes membranaires telles que la 5-nucléotidase et la Na⁺/K⁺ ATPase.Il est prévisible que les adjuvants de l'immunité ont une spécificité de cible et qu'une même substance peut se révéler stimulante ou inhibitrice selon la dose utilisée.

     

Subclinical pneumonia associated with an experimental adenovirus infection in the domestic fowl and the effect of concurrent infectious laryngotracheitis virus.

A CELO-type adenovirus (AV) isolated from fowls with respiratory disease was inoculated experimentally into the tracheas of young birds. No symptoms referable to respiratory infection were evident. Post mortem examination between days 2 and 5 after inoculation revealed pneumonia involving up to 30 per cent of the surface of the lungs. Histologically, a focal to diffuse interstitial lymphocytic infiltration and bronchiolar degeneration were present. Concurrent infections with a mild strain of infectious laryngotracheitis virus (ILT) failed to enhance the pathogenicity of either the AV or ILT infections.     

Tolerance breaking by lymphocyte activating factor induced by Escherichia coli O138 lipopolysaccharide from homologous macrophages.

Following an antigenic dose of 10 microgram or a tolerogenic dose of 200 microgram of Escherichia coli O138 lipopolysaccharide (LPS), BALB/c mice were examined on day 14 for percentages of theta-bearing cells. A considerable increase in T cells was noticed in lymphocytes from tolerant draining lymph nodes, and furthermore these cells did not possess receptors for LPS when tested for rosette inhibition. However, when the supernatant from 1 X 10(7) macrophages, pretreated with 150 microgram LPS, was given to tolerant mice on day 7, by day 14 tolerance was found to be broken, anti-LPS IgG was present in circulation and the draining lymph node contained T cells specifically committed to LPS. The change from suppressor to helper T cell activity is discussed in relation to enhancement of the immune response.     

Fish oil-induced yellow fat disease in rats. II. Enzyme histochemistry of adipose tissue

Adipose tissue in various stages of fish oil-induced yellow fat disease in the rat had the same acid phosphatase and 5-nucleotidase activity pattern as similar stages of the disorder in mink and pig. A weak acid phosphatase and 5-nucleotidase activity was seen in interstitial lipofuscin-laden macrophages in "stage M" yellow fat disease without fat cell degeneration. Activity of these macrophagic enzymes increased when there was fat cell degeneration ("stage S" and "stage E" yellow fat disease). This different phosphatase activity in the same cell type may result from phagocytosis of substrates with variable digestibility. Macrophages directly surrounding affected fat cells in steatitis areas ("stage S" and "stage E") had strong acid phosphatase and 5-nucleotidase activity. As in the pig, increased 5-nucleotidase activity was found in affected fat cells, which probably indicates plasma membrane damage. Increased nonspecific esterase activity occurred around affected fat cells. Only a small part of this esterase activity originated from inflammatory cells. This indicates that an increase of esterase activity in degenerating adipose tissue may be an endogeneous process in this tissue.