Aspects of pathogenesis and pathology of vascular lesions in Border
disease of sheep have been investigated.
Morphologically the lesion is recognised by the development of microscopical
lymphocytic-aacrophagic nodules, located mainly in the adventitia of small
arteries and arterioles of certain tissues especially CHS, In addition there
were minor degenerative changes, characterised by the fragmentation of the
nuclei of infiltrating and smooth muscle cells in the outer layers. Lightand electron- microscopically and histochemically virtually all the cells of
the infiltrate are typical- and atypical- lymphocytes and macrophages.
Evidence is provided that the lymphocytes originate from circulation and after
traversing the arteriolar wall lodge in the adventitia. Occasional cells
identified morphologically and histochemically as neutrophils could not be
confirmed electron-microscopically. Plasma cells and their precursors were
entirely absent in the infiltrate. Evidence of phagocytic activity in
macrophages was obtained from the M findings of secondary lysosomes,
phagocytosed and free necrotic cell debris, reiidual bodies and an unidentified
structure. However, M did not demonstrate cells rich in intracytoplasmic Rdft
or polyribosomes i.e. plasma cells capable of producing free antibodies. Nor
did JiM demonstrate localisation of circulating antigen-antibody complexes, and
no viral particles were evident at the magnification used. Furthermore, there
was no evidence of fragmentation or duplication of the elastic laminae,
proliferation and transformation of smooth muscle cells, fibrinoid degeneration
or fibrin deposition. The results with the FITC conjugated rabbit anti-sheep
fibrin serum eliminated the slightest possibility there being minute fibrin
deposits in affected vessels. The lesion appeared similar in all of the affected
blood vessels and no healing was observed.
Histochemical techniques for lipid revealed droplets which according to their
staining characteristics and extraction results are considered to be hydrophilic
lipids probably cholesterol, cholesterol esters and triglycerides. These were
present in and between the cytoplasm of infiltrated cells in the adventitia and
occasionally were observed in the media of affected blood vessels. On the
basis of their location, and the type of blood vessel affected, it is deduced
that they are possibly due to minor degenerative changes in the media.
study of the conditions under which the vasculitis was observed, revealed
that the lesion i3 present only in infected animals and is therefore one of the
manifestation of Border disease agent per se. However, vasculitis in both
progeny and ewes i3 dependent upon gestational age at infection —> 82 days for
progeny and < 70 days for mothers. The optimum time to produce vasculitis, in
terms of gestation is 110 days, when in two consecutive experiments 83% (10/12)
and 10a% (8/8) take was obtained in the related sub-groups.
A breed difference was also noticed during three consecutive experiments
using Cheviot x Dorset-Horn (C x DH) and pure Dorset-Horn (DH) lambs, where
C x DH lambs produced the lesion at earlier gestational ages, i.e. at 90 days
gestation a period where DH failed to show the lesion
Observations on a few goats revealed that the caruncular lesion can also
occur in species other than sheep.
The earliest time post-inoculation that the clearly developed lesion was recognised was
21 days in progeny and 17 days in ewes
It was found that the predilection site of the lesion is brain in progeny,
whilst in the dam the lesion is only present in the caruncles. However, in
progeny, vasculitis was also found in brain, spinal cord, epididymis, lung,
mammary gland, sciatic nerve, heart, adipose tissue of kidney and lymph nodes,
kidney, spleen, lymph node and skin in descending order of frequency.
Consideration of the relationship of the Border disease induced vasculitis
to age at infection and survival time led to the hypothesis of an immune response
associated with localisation of antigen on the blood vessel wall. In view
of absence of demonstrable antibodies this immune response seemed likely to
be either type III or type IV allergic reaction of the classification of
Coombs and Gell (1968). With the direct and indirect inmiuno-fluorescent
techniques, using conjugated and unconjugated hyperimmune serum against
Border disease and rabbit anti-sheep IgG the localisation of antigen was
demonstrated on the blood vessel wall. In vivo macrophage disappearance
test applied to lambs and guinea-pigs sensitised with Border disease agent,
showed 18.9%- and 37.6% drop in the number of macrophages in the peritoneal
exudate, compared with controls. These results support the immune hypothesis
and favour a type IV allergic reaction.
It was found that the lesion was confined to arterioles and small
distributing arteries. Infiltration of cells to the adventitia increased
the thickness of this coat, resulting in an overall increase of wall thickness
and consequently increased arteriolar ratio i.e. 1: 0.7
The lesion was studied by montage of tracings of serial, H & E stained
paraffin sections and found to consist of microscopic nodular swellings in
the adventitia along the course of the affected vessels. These nodules are
60-282 μ in length and show a unilateral or bilateral segmental distribution
with intervals of from 48-82 μ.
Comparison of Border disease induced vasculitis with other vascular
conditions of mammals suggests that though there are some similarities to
both periarteritis nodosa and the vascular changes of sex-urn sickness these
are so minor that the Border disease associated vasculitis may be considered
a unique and separate entity.
