Biomedical subjects
Publications and source records attributed to C R Stokes.
We have examined the morphology and functional characteristics of porcine intraepithelial lymphocytes (IEL). A subpopulation of IEL contains granules as seen in other species, and their ultrastructure was also similar. They were capable of producing T-cell growth factor and interferon on in vitro stimulation. IEL killed P815 cells in the presence of PHA, but did not kill K562 cells.
Intranasal vaccination with a cold-adapted strain of feline herpesvirus type 1 (FHV-1) two days before challenge gave partial protection, and four days before challenge gave complete protection, against feline viral rhinotracheitis. Protection at this time appeared to be specific since vaccination with FHV-1 did not affect the disease caused by the unrelated feline calicivirus. The time course of onset of protection also confirmed that the protective mechanism was likely to be specific. However, six days after vaccination only low levels of FHV-specific IgA and IgM antibody and of interferon were found in serum and nasal washings. In lymphocyte transformation assays neither peripheral blood lymphocytes nor tonsil lymphocytes gave a significant proliferative response in the presence of FHV antigen. Pathogenesis experiments demonstrated that the tonsil and nasal turbinates were the most important sites of virulent FHV-1 replication. Vaccination significantly reduced levels of infectious virus found in both sites. The results provide evidence that no one mechanism is responsible for protection following vaccination but local specific responses are more likely to be involved.
Intraepithelial lymphocytes (IEL) were isolated from the small intestine of pigs. They showed a strong blastogenic response to the T-cell mitogens phytohaemagglutinin A (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM); in contrast, mouse IEL responded weakly to these mitogens. The response of pig IEL was age-dependent, reaching adult levels by 9 weeks of age. Early weaning of pigs delayed the onset of this response. The effects of inflammatory mediators on the response of mouse IEL were also examined.
Antibody in serum, uterine and vaginal secretions was measured following local immunisation and experimental infection with the organism of contagious equine metritis (Taylorella equigenitalis). Intrauterine immunisation with killed T equigenitalis stimulated a systemic IgG titre and a uterine IgA and IgM response. Subsequent challenge with the organism, however, resulted in a characteristic metritis in both control and vaccinated mares. Antibody in serum and secretions was increased following challenge infection, dwarfing the response to immunisation. The local response was restricted to the IgA and IgM classes in both uterine and vaginal secretions. There was no elevation in local IgG antibody, although there was an increase in serum IgG in response to challenge infection. A second experimental challenge, following natural resolution of the initial infection and a period of reimmunisation, resulted in reduced clinical signs and bacterial isolation rates from both control and vaccinated mares, but no absolute protection from infection.
The effect of cycle stage on immunoglobulin and albumin levels in serum, follicular fluid, oviductal, uterine and vaginal secretions was measured. There was no variation in serum immunoglobulin levels during the oestrous cycle, although IgM levels were elevated in cyclic mares compared to non-cyclic (immature and anoestrous) animals. Similarly, there was no cyclical variation in follicular or oviductal protein concentrations. In the uterus, IgG and IgA levels relative to total protein were higher in oestrogenic than in progestagenic secretions, while the trend in relative IgM concentrations was reversed. Albumin levels were unchanged. In mares sampled repeatedly from the uterus and vagina during a single oestrous cycle, protein levels in secretions were affected by the collection technique. However, there was variation in absolute IgG, IgA, albumin and total protein concentrations, with maxima during dioestrus and minima at oestrus. Protein concentrations were higher in vaginal than in uterine secretions, although IgA relative to total protein was higher in the uterus than the vagina.
This study identifies nonimmune binding of equine immunoglobulin by the causative organism of contagious equine metritis. Immunoglobulin binding to the bacterium was strongest for immunoglobulin G (IgG) and less for IgM; IgA was not bound. Binding of equine IgG was inhibited by human IgG, but not by IgG of domestic animals. Immunoglobulin binding by the bacterium appeared to be directed towards an epitope in the hinge region of the immunoglobulin molecule.
The immunoperoxidase technique was adapted for the identification of free immunoglobulin and immunoglobulin producing cells in equine tissues. Staining specific for free IgG, IgA and IgM was detected at all levels of the reproductive tract, and secretory component staining was present in the uterine epithelium but not in the oviduct, cervix or vagina. Immunoglobulin producing cells were present at all levels of the tract, with IgG and IgA cells at equivalent concentrations, but with fewer IgM cells. There was no cyclical trend in free immunoglobulin staining, or plasma cell numbers. IgG and IgM plasma cell numbers declined from uterus to vagina, as did epithelial staining, and the ratio of IgG:IgA cells declined from oviduct to vagina.
An enzyme-linked immunosorbent assay (ELISA) was adapted for the horse to investigate the production of antibody in response to subcutaneous, intrauterine or intravaginal immunization with dinitro-phenylated human serum albumin. An IgM response was not detected, but antibodies of the IgGab, IgGc, IgGT and IgA isotypes were measured in serum, uterine and vaginal secretions. Local immunization produced antibody titres in serum and secretions, with evidence of significant local production.
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Five-day-old pigs challenged with 10(3) pathogenic Escherichia coli (nalidixic acid resistant) showed no clinical signs of disease until subsequently weaned at three weeks. Dietary manipulation was shown to influence xylose malabsorption, diarrhoea and bacterial proliferation after weaning. Brief, but not continuous, contact with the diet before weaning markedly increased the severity of subsequent disease after weaning. Immunogenicity of the weaning diet was critical for the development of the disease. Two diets, identical except that in one the protein source (casein) had previously been enzymatically hydrolysed, were compared. Pigs fed the predigested diet showed no clinical signs of post weaning diarrhoea whereas those fed the untreated casein all developed diarrhoea.
Food was given to pigs before weaning to determine whether a hypersensitive response to dietary antigen might be a predisposing factor to postweaning diarrhea. Small amounts of food increased the severity and accelerated the onset of postweaning diarrhea. Postweaning diarrhea was dependent on the presence within the diet of antigenic material (bovine casein). A weaning diet, containing little antigenic material (hydrolyzed casein), had less effect on sucrase concentration in intestinal brush borders than did diets rich in antigens (native casein). Seemingly, immune-mediated intestinal damage may predispose the pig to postweaning diarrhea.
IgG, IgA, IgM and albumin concentrations were measured in serum, follicular fluid and oviductal, uterine and intestinal secretions of the horse. Follicular protein concentrations were found to be dependent on serum concentration and molecular size. Of the immunoglobulins only IgG was detectable in oviductal secretions, but IgG:albumin ratios did not differ significantly from those in serum. IgG, IgA and IgM were measured in uterine secretions, with IgG predominant. Serum transudation into uterine secretions was minimal. In intestinal secretions, IgA levels were slightly higher than IgG, with albumin and IgM at low levels. In five mares with histories of chronic metritis, IgG, IgA and albumin concentrations were significantly elevated in uterine secretions.
Immunoglobulin quantitation of fluids obtained from several regions of the female reproductive tract indicated the presence of IgG, IgA and IgM. IgG was almost invariably present in greatest amounts and IgM always made the smallest contribution. Although much of this immunoglobulin was derived from serum, evidence of the molecular size of IgA, the IgA and IgG ratios and that obtained from experiments involving the injection into sows of 125I-labelled immunoglobulin indicated that local synthesis within the tract also occurred.
Oral immunization with 25 mg/day of ovalbumin resulted in a number of changes in non-specific immune responsiveness, including increases in antibody produced to T-dependent but not T-independent antigens and the abrogation of tolerance induced by both oral and intravenous routes. The effect was transient, sex- and strain-dependent. Evidence suggests that it is a consequence of cell-mediated immunity to the oral immunogen.
Experiments were undertaken to investigate whether a hypersensitivity response to dietary antigen might be a predisposing factor in the aetiology of post weaning diarrhoea. The results indicated that: 1. very small amounts of food given to baby pigs before weaning significantly increased the severity and accelerated the onset of the disease; 2. post weaning diarrhoea was dependent upon the presence within the diet of antigenic material; 3. weaning diets containing little antigenic material had less effect upon sucrase levels in the brush borders than did diets rich in antigens. These results are discussed in relation to the hypothesis that immune mediated intestinal damage may predispose to post weaning diarrhoea.
The effect of feeding ovalbumin was studied in CBA, C3H, SWR/J and A inbred strains of mice. In non-immune animals differences were observed in their abilities to absorb intact antigen and eliminate it from their circulation. Following oral immunization, C3H mice were able to absorb significantly less ovalbumin than controls, however no evidence for immune exclusion was found in the other strains. Oral tolerance could be induced in all strains tested but in CBA and SWR/J mice oral immunization had to be continual, via the drinking rather than a single daily gastric intubation. The results suggest that genetic differences exist in the handling of antigen by the gut. If similar differences exist in man they may underly differences in susceptibility to food allergy.