#1. The method of investigating the seat of
origin of antibodies, especially the haemolysins,
bactericidal bodies and precipitins, by means of
"Organ extracts" is valueless: and no reliance
can be placed on results derived by such a method.
#2. Normal rabbits, injected intravenously
with ox blood corpuscles, show Immune body, in
their blood, against ox blood corpuscles, for the
first time, on or about the third day.
#3. Normal rabbits, from which the spleen
alone, the spleen and thyroid, the thyroid alone,
or one Kidney has been removed and into which,
within a week or so after the operation, ox blood
corpuscles have been injected intravenously, show,
like the controls, Immune body, against ox blood
corpuscles * for the first time on or about the
third day.
#4. The total leucocyte count of perfectly
normal rabbits may vary in different individuals
between roughly 4,000 and 15,000; in individual
rabbits, in ordinary and exaggerated conditions
of laboratory life, as regards feeding time of
day &c., the total leucocytes do not vary beyond
3,000 on either side of a mean per Cram,that is
beyond the limits to be allowed for experimental
error.
#5. The differential count, as regards
polymorphonuclears and lymphocytes, varies so
much, under ordinary laboratory conditions, in
the same rabbit, at different times, and in
different rabbits, that conclusions should be
drawn, with great caution, from any variation
under experimental conditions.
#6. The spleen was removed from a normal
rabbit. Two days after its removal, it was
injected intravenously with ox blood corpuscles.
Immune body appeared in its blood in three days
and yet there was no leucocytosis. To adopt the
usual criterion this may be taken as evidence
that a compensatory action on the part of the
hone marrow and lymphatic apparatus has been excluded.
#7. Injections into normal rabbits, intravenously, intraperitoneally, and subcutaneously,
of even large amounts of ox blood corpuscles
do not produce a variation in the total leucocyte
count beyond that in control animals.
#8. Such injections, - and I speak here
with the greatest caution - produce no effect on
the differential count.
#9. From the above results, I would conclude provisionally, that so far as such methods
can settle such a question, there is great
probability that neither, the spleen, nor the
bone marrow, nor the lymphatic apparatus, nor
the kidney, is the seat of formation in rabbits,
of Immune body against ox blood corpuscles.
#10. Normal rabbits, from whom blood,
a haemoiysin, agglutinin and precipitin for ox
blood has been carefully excluded, after being
fed for some time on ox blood, show in their
blood all of these active principles. This
gives some support to the view, to be advanced
in this paper, that the formation of antibodies
is allied to the ordinary physiological processes
of assimilation: and as the liver is accredited
by physiologists with a high role in such processes, to the liver being regarded provisionally as a possible seat of formation of Immune body, -
(for sensitised ox blood corpuscles.
#11. The amount of complement in leech,
citrate, fluoride, and oxalate plasmas of the
rabbit is the same as in the corresponding leech,
citrate, fluoride, and oxalate sera.
#12. Normal aqueous humour of rabbits and
the fluid from a tape worm cyst of the rabbit,
do not contain complement for sensitised ox blood
corpuscles. They are both highly specialised
secretions.
#13. The fluid that collects in a short
time after puncture in the anterior chamber of
the eye and Blister fluids do contain, such
complement. They are both of the nature of
transudates from the blood vessels.
#14. As showing the highly specialised
nature of the secretion in the anterior chamber
of the eye, some rabbits, with a blood serum, of
very high titre in Immune body against ox blood
corpuscles, may have none of this Immune body in
even 0.5cc of their aqueous humour).
#15. Normal rabbits may be bled to the extent
of more than one third of their blood at one
sitting, or of more than one half within 18 hours
without showing any change in the complement content of their serum for sensitised ox blood corpuscles .
#16. If a normal rabbit, whose blood has
been ascertained to be free from Immune body
against ox blood corpuscles, be injected intravenously with a large amount of ox blood corpuscles - 28cc equivalent to 56cc defibrinated
blood - the ox blood corpuscles can be recognised
in the rabbit's general circulation until about
the third day. At that time there is a critical
formation of Immune body, a critical disappearance
of the ox blood corpuscles, and a critical
haemoglobinuria. contrary to what Sachs found,
I did not observe any variation in the complement
content for ox blood corpuscles in such an experiment.
#17. The infection intravenously into normal
rabbits of unsensitised ox blood corpuscles, even
in very large quantity, does not produce any
diminution of complement. The injection intravenously into normal rabbits, of an amount of
sensitised or saturated ox blood corpuscles
calculated to be sufficient to use up all the
complement in the rabbit's body produces no
reduction of the complement, while the injection
of four times the calculated amount of such
corpuscles into a similar rabbit, produces a
scarcely perceptible diminution of the complement.
On the other hand, the injection intravenously
into rabbits, which have been immunised against
ox blood corpuscles, of a quantity of fresh,
sensitised, or saturated corpuscles far from
sufficient to use up all the calculated amount
of complement in the animal's body, markedly reduces the complement content of the animal's blood.
Such animals often die rapidly. The possible
explanation of both Phenomena may be,that the
sudden lysis sets free stromata, which absorb the
complement and further block the capillaries of
the lung and other organs.
#18. If a normal rabbit be injected intraperitoneally
with inactivated Immune serum
against rabbit corpuscles, obtained by injecting a guinea pig with rabbit corpuscles, this heated immune serum appears to be absorbed into the
rabbits bloodyto find complement there free in the
blood, to unite with it and to cause extracellular
haemolysis of the rabbi'ts red blood corpuscles and
intense haemoglobinuria.
#19. There is great probability therefore,
that complement exists, free in the circulating
plasma of the blood, and that, further, the organ,
producing complement, must be one of great metabolic
activity and of exceptional powers of regeneration.
#20. The extirpation of the spleen and of the
thyroid in rabbits may be said to cause no
variation in the complement content of rabbits'
serum.
#21. Taking such things in relation, with
the positive findings of Nolf, Ehrlich &c., I submit that the liver ought to be considered as a possible seat of origin of complement.
#22. When hen corpuscles are injected intravenously into rabbits, the corpuscles tend to
accumulate and to be retained in the liver.
#23. Such corpuscles are phagocyted to a
small degree by the liver cells and Kupfer cells.
No evidence was observed for phagocytosis taking
place in the spleen or any of the other organs.
#24. The liver cells are capable of a wide
variation in morphological appearance, possibly
corresponding with a similar wide range of metabolic activity and functioning.
#25. Taking into consideration the facts
exclusive and presumptive accumulated above
concerning the seat of origin of Immune body,
the facts of the accumulation and retention of
hen corpuscles in the liver and then phagocytosis there,
and the fact of the great variation
possible in the liver cell, I submit that the
liver ought to be considered as a possible seat
of origin of immune body.
#26. To generalise, I would submit the
possibility of the formation of antibodies being,
in nature, the hypertrophy of a normal physiological process - a process which physiologically deals with overflow from the intestinal tract of
material, toxic and non toxic, fluid and particulate, multiplying and non multiplying and which has escaped the process of intestinal digestion
to which the bulk of absorbed material is subjected before absorption
