570° 
NALTORE 
[ OcTOBER 2, 1902 
attack of cow-pox or vaccinia, ‘This disease is related to small- 
pox, and some still hold that it is small-pox modified and 
rendered less malignant by passing through the body of a calf. 
At any rate, an attack of vacciniarenders a person immune to 
small-pox, or variola, for a certain number of years. Vaccination 
is an instance of what is called protectéve ¢noculation, which is 
now practised with more or less success in reference to other 
diseases like plague and typhoid fever. The study of immunity 
has also rendered possible what may be called curatcve énocuda- 
tion, or the injection of antitoxic material as a cure for diphtheria, 
tetanus, snake poisoning, &c. 
The power the blood possesses of slaying bacteria was first 
discovered when the effort was made to grow various kinds of 
bacteria in it; it was looked upon as probable that blood would 
prove a suitable soil or medium for this purpose. It was found 
in some instances to have exactly the opposite effect. The 
chemical characters of the substances which kill the bacteria 
are not fully known; indeed, the same is true for most of the 
substances we have to speak of in this connection. Absence 
of knowledge on this particular point has not, however, pre- 
vented important discoveries from being made. 
So far as is known at present, the substances in question are 
proteid in nature. The bactericidal powers of blood are destroyed 
by heating it for an hour to 56° C. Whether the substances are 
enzymes is a disputed point. So also is the question whether 
they are derived from the leucocytes ; the balance of evidence 
appears to me to be in favour of this view in many cases at 
any rate, and phagocytosis becomes more intelligible if this 
view is accepted. The substances, whatever be their source or 
their chemical nature, are sometimes called alexins, but the 
more usual name now applied to them is that of Jacterio- 
lysins. 
Closely allied to the bactericidal power of blood, or blood- 
serum, is its globulicidal power. By this one means that the 
blood-serum of one animal has the power of dissolving the red 
-blood-corpuscles of another species. If the serum of one animal 
is injected into the blood-stream of an animal of another species, 
the result is a destruction of its red corpuscles, which may be 
so excessive as to lead to the passing of the liberated hemo- 
globin into the urine (hemoglobinuria). The substance or 
substances in the serum that possess this property are called 
haemolysins, and though there is some doubt whether bacterio- 
lysins and heemolysins are absolutely identical, there is no doubt 
that they are closely related substances. 
Another interesting chemical point in this connection is the 
fact that the bactericidal power of the blood is closely related to 
its alkalinity. Increase of alkalinity means increase of bacteri- 
cidal power. Venous blood contains more diffusible alkali than 
arterial blood and is more bactericidal ; dropsical effusions are 
more alkaline than normal lymph and kill bacteria more easily. 
In a condition like diabetes, when the blood is less alkaline 
than it should be, the susceptibility to infectious diseases is in- 
creased. Alkalinity is probably beneficial because it favours 
those oxidative processes in the cells of the body which are so 
essential for the maintenance of healthy life. 
Normal blood possesses a certain amount of substances which 
are inimical to the life of our bacterial foes. But suppose a 
person gets run down; everyone knows he is then liable to 
*‘catch anything.” This coincides with a diminution in the 
bactericidal power of his blood. But even a perfectly healthy 
person has not an unlimited supply of bacteriolysin, and if the 
bacteria are sufficiently numerous he will fall a victim to the 
disease they produce. Here, however, comes in the remarkable 
part of the defence. In the struggle he will produce more and 
more bacteriolysin, and if he gets well it means that the bacteria 
are finally vanquished, and his blood’ remains rich in the par- 
ticular bacteriolysin he has produced, and so will render him 
immune to further attacks from that particular species of bac- 
terium. Every bacterium seems to cause the development of a 
specific bacteriolysin. 
Immunity can more conveniently be produced gradually in 
animals, and this applies, not only to the bacteria, but also to 
the toxinsthey form. If, for instance, the bacilli which pro- 
duce diphtheria are grown ina suitable medium, they produce 
the diphtheria poison, or toxin, much in the same way that 
yeast-cells will produce alcohol when grown in a solution of 
sugar. Diphtheria toxin is associated with a proteose, as is also 
the case with the poison of snake venon, If a certain small 
dose called a ‘‘lethal dose” is injected into a guinea-pig, the 
result is death. But if the guinea-pig receives a smaller dose it 
NO. 1718. VOL. 66] 
will recover ; a few days after it will stand a rather larger dose ; 
and this may be continued until after many successive gradually 
increasing doses it will finally stand an amount equal to many 
lethal doses without any ill effects. The gradual introduction 
of the toxin has called forth the production of an antitoxin. If 
this is done in the horse instead of the guinea-pig the produc- 
tion of antitoxin is still more marked, and the serum obtained 
from the blood of an immunised horse may be used for injecting 
into human beings suffering from diphtheria, and rapidly cures 
the disease. The two actions of the blood, antitoxic and 
| antibacterial, are frequently associated, but may be entirely 
distinct. 
The antitoxin is also a proteid probably of the nature of a 
globulin; at any rate, itis a proteid of larger molecular weight 
than a proteose. This suggests a practical point. In the case 
of snake-bite the poison gets into the blood rapidly owing to the 
comparative ease with which it diffuses, and so it is quickly 
carried all over the body. In treatment with the antitoxin or 
antivenin, speed is everything if life is to be saved ; injection of 
this material under the skin is not much good, for the diffusion 
into the blood is too slow. It should be injected straight away 
into a blood-vessel. 
There is no doubt that in these cases the antitoxin neutralises 
the toxin much in the same way that an acid neutralises an 
alkali. If the toxin and antitoxin are mixed in a test-tube and 
time allowed for the interaction to occur, the result is an 
innocuous mixture. The toxin, however, is merely neutralised, 
not destroyed ; for if the mixture in the test-tube is heated to 
68° C. the antitoxin is coagulated and destroyed and the toxin 
remains as poisonous as ever. 
Immunity is distinguished into actzve and fasseve. Active 
immunity is produced by the development of protective substances 
in the body ; passive immunity by the injection of a protective 
serum. Of the two the former is the more permanent. 
Ricin, the poisonous proteid of castor-oil seeds, and aérin, 
that of the Jequirity bean, also produce when gradually given to 
animals an immunity, due to the production of antiricin and 
antiabrip respectively. 
Ehrlich’s hypothesis to explain such facts is usually spoken of 
as the side-chain theory of immunity. He considers that the 
toxins are capable of uniting with the protoplasm of living cells 
by possessing groups of atoms like those by which nutritive 
proteids are united to cells during normal assimilation. He 
terms these Aap/ophor groups, and the groups to which these are 
attached in the cells he terms receptor groups. The introduc- 
tion of a toxin stimulates an excessive production of receptors, 
which are finally thrown out into the circulation, and the free 
circulating receptors constitute the antitoxin. The comparison 
of the process to assimilation is justified by the fact that non- 
toxic substances like milk introduced gradually by successive 
doses into the blood-stream cause the formation of anti-sub- 
stances capable of coagulating them. 
Up to this point I have spoken only of the blood, but month 
by month workers are bringing forward evidence to show that 
other cells of the body may by similar measures be rendered 
capable of producing a corresponding protective mechanism. 
One further development of the theory I must mention. At 
least two different substances are necessary to render a serum 
bactericidal or globulicidal. The bacteriolysin or hemolysin 
consists of these two substances. One of these is called the 
zmmune body, the other the complement. We may illustrate the 
use of these terms by an example. The repeated injection of 
the blood of one animal (e.g. the goat) into the blood of 
another animal (e.g. a sheep) after a time renders the latter 
animal immune to further injections, and at the same time 
causes the production of a serum which dissolves readily the 
red blood-corpuscles of the first animal. The sheep’s— 
serum is thus hemolytic towards goat’s blood-corpuscles. 
This power is destroyed by heating to 56° C. for half 
an hour, but returns when fresh ‘goat’s serum is 
added. The specific immunising substance formed in the 
sheep is called the immune body; the ferment-like substance 
destroyed by heat is the complement. The latter is not specific, 
since it is furnished by the blood of non-immunised animals, 
but it is nevertheless essential for hemolysis. Ehrlich believes 
that the immune body has two side groups—one which connects 
with the receptor of the red corpuscles and one which unites 
with the haptophor group of the complement, and thus renders 
possible the ferment-like action of the complement on the red 
corpuscles. Various antibacterial serums which have not been 
