Strategies for exploiting the immune system in the design of vaccines.

There are three types of vaccines in medical use today--live, attenuated agents, mainly viruses; inactivated whole organisms; and subunit preparations. Though there are examples in each category of successful preparations, live attenuated viruses have almost invariably given long-lasting immunity after one or two administrations. Contributing reasons for this are gleaned, not from human vaccine studies, but from model systems and it is concluded that a vaccine needs to achieve four goals: activation of antigen-presenting cells; overcoming genetic variability in T cell responses; generation of high levels of T and B memory cells; and persistence of antigen for recruitment of B memory cells. Of the newer approaches to vaccine development, synthetic peptides have substantial limitations but should be successful in some cases. Subunit preparations may also be limited as a general method. Some live viral or bacterial vaccines, used as vectors of nucleic acid coding for other antigens, hold considerable promise as is illustrated by recent examples.

[Intestinal permeability disorders in children]. / Perturbations de la perméabilité intestinale chez l'enfant.

The intestinal mucosa has a certain degree of "porosity", which allows some molecules and macromolecules that are not subject to active transport, to cross the intestinal wall and enter the blood circulation. This permeability of the intestinal mucosa, which depends mostly on the size of the molecule and the state of the mucosa, can be studied with the assistance of protein macromolecules in an allergy-immunological investigation, or with inert markers, so permitting evaluation of the state of integrity of the small intestine. The markers used are polyethylene glycols (PEG) of various molecular weights, Cr EDTA, the monosaccharide sugars mannitol or rhamnose and the disaccharide sugars lactulose or cellobiose. Study of the intestinal permeability to inert markers allows detection of coeliac or Crohn's disease. It can be repeated, especially at the time of food provocation tests needed in the diagnosis of food intolerances in pediatrics in the enteropathology to cows milk proteins, atopic dermatitis and irritable colon in children.

Measurement of back clearance.

With improvement in dialysis membranes, back filtration becomes the focus of study. Because new membranes that remove low molecular weight proteins, such as beta 2-microglobulin by diffusion are now available for clinical use, both back filtration and back diffusion become problems. This paper gives the mass transfer rate of solutes from the dialysate to blood compartment. As markers of toxic or antigenic substances, inulin (MW 5,200), lysozyme (MW 14,300), and alpha-lactoalbumin (MW 14,400) were used. The dialyzers tested were the CLSU-12W, AM-FP10, BK-1.0P, and FB-110U. The UFR controller set the flow rate on the blood side at 200, dialysate at 500, and ultrafiltration (QF) as 0 to 50 ml/min. Under these conditions, the inulin back clearance is 16 (CLSU) to 26 ml/min (FB), even if the QF is 50 ml/min, and is 10 to 34 ml/min for lysozyme at QF = 0 ml/min. Although a substantial amount of solute moves into the blood compartment, back clearance does not drastically decrease with increase in QF. To avoid contamination of the blood side, clean-up techniques for the dialysis line or online protein adsorber should be followed.

Melano-macrophage centers in the aglomerular kidney of the sea horse (teleosts): morphologic studies on its formation and possible function.

In order to elucidate the process of the formation and possible function of the renal "melano-macrophage centers (MMC)" of fish, light and electron microscopic observations were carried out on the aglomerular kidney of the sea horse, Hippocampus kuda BLEEKER, injected with antigenic horse-spleen ferritin (AF) and nonantigenic carbon particles (CP). Kidneys of the sea horse have well-developed hemopoietic foci in the interstitial tissues surrounding the bundles of renal tubules. Each hemopoietic focus has a small artery in the central area and is framed with the densely arranged sinusoids lined with monolayered macrophages which have no melanin pigments. In the hemopoietic foci free macrophages (M phi) were hardly found, but large clusters of MMC filled with densely packed masses of cell debris with some melanin pigments were encountered. Some of them had degenerated M phi with fibrotic change surrounded by fibroblasts. AF and CP injected intraperitoneally entered quickly into blood vessels and were taken up actively by the sinusoidal M phi. The M phi full of AF or CP left the sinusoidal wall and moved gradually into hemopoietic foci to form the MMC or to fuse with the preexisting MMC. The melanophores in the interstitial connective tissue joined to form the MMC. No specific histologic change suggestive of immune response to the AF was present in and around the MMC. The results indicate that the MMC of fish should be only the aggregates of M phi to digest the ingested materials effectively. The process of formation of MMC and their possible function is discussed.

Effect of rotavirus infection and malnutrition on uptake of a dietary antigen in the intestine.

Intestinal absorption of ovalbumin (OVA), a dietary macromolecule, was studied in malnourished and normally nourished suckling mice after experimentally induced infection with rotavirus. All mice developed diarrhea within 24 to 48 h postinoculation. The malnourished animals exhibited more severe symptoms and an increased number of rotavirus-containing enterocytes in intestinal sections as compared to well-nourished mice when examined 3 d postinoculation, at the peak of diarrhea. Histopathologic examination revealed villus atrophy and pronounced vacuolization of villus enterocytes in association with malnutrition and rotavirus infection. The combination of malnutrition and viral infection resulted in more severe mucosal damage, including disruption of microvillus borders. After a single oral dose of 100 micrograms OVA at 3 d postinoculation, the concentration of OVA in serum, gastric content, intestinal lavage fluid, and intestinal tissue homogenates was measured at different time intervals. The concentrations of OVA in intestinal tissue were significantly higher in malnourished animals, whereas lower values were found in rotavirus-infected animals. In all mice, OVA was rapidly absorbed and could be consistently detected in the serum within 5 min. OVA levels peaked at 45 to 60 min and then gradually declined. In malnourished infected animals, the uptake of OVA was rapid and resulted in significantly higher serum levels when compared to well nourished or uninfected controls, respectively. The peak uptake of OVA per g body wt was about 4.5 times more in malnourished infected compared to well-nourished infected mice and 2.5 times higher in normally nourished infected animals when compared to uninfected controls. These results indicate that rotavirus infection in association with malnutrition may cause a significant rise in gut permeability to environmental macromolecules.