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Title: The immune response of the mouse to the intestinal trematode Diplostomum phoxini (Faust, 1918)
Author: Mawdsley, Melody Ann
ISNI:       0000 0001 3621 7808
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1983
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It was found that starvation of CFLP and NIH mice for six hours prior to infection was sufficient to produce a marked improvement in the level and consistency of establishment of oral infections of D. phoxini metacercariae, if the mice were starved from 6 AN, allowing stomach emptying to occur before infection. In contrast to spermatogenesis, the detection of vitellogenesis and oogenesis in D. phoxini in the NIH mouse was markedly delayed compared with that reported in the duckling. There was no difference in establishment or loss of a 200 metacercarial oral infection in male and female NIH mice. Loss began on day 6 and was complete by day 11 pi. Growth of flukes was complete by day 3. Flukes were largely confined to the anterior 10 cm of small intestine until the loss phase, when some attached to the region 10-20 cm post pylorus before being lost. The method used detected a very low rate of egg production which declined rapidly after the onset of the loss phase of infection, although at this time there was not a corresponding decline in the percentage of flukes bearing eggs* Implantation of metacercariae into different regions of the small intestine led to the following conclusions. 1. Establishment was best 30-60 % post pylorus, and very poor in the posterior 40% of the small intestine. Inconsistent establishment in the anterior duodenum could be due to lack of preincubation, combined with other factors. 2. Recovery of flukes five days after transplantation of metacercariae was best in those implanted in the anterior 30% of the small intestine and the percentage of egg bearing flukes was highest in the anterior 10 cm of small intestine. 3. Flukes that survived until day 5 were the same size if found near to the site of implantation. Those which had moved in a posterior direction were smaller.Reduction of infection size from 400 to eight metacercariae resulted in a four day delay in expulsion of primary infection, which otherwise occurred normally. Some delay in growth of flukes in a 400 metacercarial infection may have been due to changes in the gut preceding expulsion. Cortisone acetate treatment delayed the onset of main fluke loss, which occurred after day 13 pi, by which time a normal primary infection was completely removed. 11% of flukes still remained on day 25 pi in treated mice. It is suggested that this represents loss due to senescence, or to a delayed, reduced immunological response. Flukes in cortisone acetatetreated mice were large (comparable to those from low level infections) and remained in the anterior 10-15 cm of the small intestine. Serial transplantation also resulted in increased longevity of flukes but losses were greater, probably due to the trauma of recovery and transplantation. Transplantation of flukes undergoing expulsion resulted in their reestablishment in naive donors, though once again losses occurred. Transplanted flukes then had a longevity similar to that of flukes in an oral primary infection. The results indicate 1. Expulsion of a primary infection is host-mediated. 2. D. phoxini is highly immunogenic as the expulsion of light infections (eight metacercariae) is similar to that of infections initiated by 400 metacercariae. 3. Damage to flukes is reversible, as shown by the establishment and survival of flukes in the process of expulsion, upon transfer to naive hosts. The characteristics of a 200 metacercarial secondary infection (administered three weeks after a 200 inetacercarial primary infection) are described. After normal establishment, rejection occurred between two and four days post infection. Fluke development was impaired, functional vitellaria did not form and eggs were not produced. Growth stopped before day 2 pi. No waning of immunological memory occurred when the interval between primary and secondary infections was increased to seven months. Reduction of the size of the immunizing infection to as few as five metacercari ae resulted in no reduction in the effect of the immune gut on the rate of expulsion of secondary infection, although the inhibitory effect on fluke growth was less marked. Abbreviation of a 200 metacercarial to 15h duration apparently did not diminish resistance of mice to subsequent reinfection. The effects of the immune gut on the growth, development and longevity of D. phoxini were found to be reversible when flukes from a secondary infection were transplanted into a naive host. The effect of the immunized gut on transplanted, almost mature (three day old) flukes from primary infection was less marked than the effect on metacercariae surgically implanted into the duodenum, survival of the three day old flukes in immune mice was almost as long as would be expected in primary infection, and development proceeded to completion. Serum from mice infected with D. phoxini eight days previously failed to transfer immunity. Immunity transferred adoptively by IMLNC was manifested as an acceleration of expulsion, and a retardation of vitelline development and reduced growth of flukes in recipient mice compared with controls. As few as 1x107 IMLNC affected expulsion. 2x107 IMLNC affected body length and vitelline development also. IMLNC taken from donor mice between days 2 and 6 of a primary infection were most effective. After day 6, efficacy declined, however IMLNC taken from donor mice on day 21 after primary infection unexpectedly had some effect on recipient challenge infection. IMLNC taken 12 hours after secondary infection were effective but those from days 6 and 12 of secondary infection were not. I MLNC transferred less than two days before challenge of recipient mice did not transfer immunity. T. lymphoblast activity was high and cellularity of the MLN increased following primary and secondary infections, but these changes were not coastsknL correlated temporally with the efficacy of I MLNC. T-lymphoblasts were ineffective but a population of mainly non-dividing B cells was effective in transferring immunity adoptively. Histopathological changes in the mouse intestine associated with D. ph oxini infection were characterized, and the effect of adoptively transferred immunity (via IMLNC) on these parameters was studied. Infection was characterized by marked globule leukocyte proliferation and eosinophilia which preceded and accompanied the expulsion phase of infection. Both responses occurred more rapidly in secondary than in primary infection. By comparison, the response of lamina propria mast cells was delayed and very limited, and was not marked in secondary infection. The response of goblet cells to infection was minor, and irregular during normal infection, however it is possible that mucus production by individual cells may be increased during infection. Adoptive transfer of immunity led to an acceleration of all cellular responses. sIg+ve MLNC transferred immunity most effectively and generated a level of inflammation which was severe compared with normal infection, and was uncharacteristic as it involved increased goblet cell differentiation. The poor ability of T cells to transfer immunity might have been attributable to low viability and/or selective depletion during cell separation. High variability was observed in the number of plasma cells in the intestine during infection. The most marked increases occurred in lgG, and 1gM secreting plasma cells during primary infection and lgG, during secondary infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology