Jean Broadhurst.

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Agglutinins. — Sometimes the antibodies which aid the white
corpuscles may be even more strikingly demonstrated by means of
the microscope. If the serum of a person who has had typhoid
fever be added to a drop of blood containing living typhoid organ-
isms, these actively motile bacteria slow their movement and finally
come to rest sticking together in groups or clumps, often several
dozen in a clump (see p. 215 and Figs. 60 and 61). This clumping
is just what would result if they had become sticky or glutinous,
and we therefore say they have agglutinated.

^ Like opsonium, a little-used word from the Greek, which is used for any-
thing eaten as a relish, such as olives or anchovies. The term opsonins,
therefore, implies that these substances are like relishes, making the bacteria
more attractive to the white corpuscles.



It has recently been shown that this same clumping or agglutina-
tion takes place in the body as well as in drops of serum observed
under the microscope. Such clumping is the result of a protec-
tive antibody formed by the body against the bacteria, and favors
their destruction by the white corpuscles (Fig. 51). It suggests
the old recipe for cooking hares, which began : " First catch your
hare/' for these clumped or agglutinated bacteria are more easily
caught and engulfed by the white corpuscles. Motile bacteria lose

Fig. 51. — A rabbit made immune to typhoid by earlier injections of Bacillus typhosus
was later given a heavy injection of the same organism. The left photograph of blood
taken from the heart 30 seconds later shows clumps of bacilli and indicates how rapidly
agglutination took place. The agglutinated cocci (right photograph) were from a rabbit
immunized against the pneumococcus (causal organism of pneumonia) and injected similarly
with pneumococci.

their power of movement ; the large clumps stick to the walls of the
blood-vessels, or are delayed in the smaller capillaries ; they are held
back in such glands as the lymph "nodes'' (G), and so are more
promptly disposed of by the white corpuscles.

It has been suspected for some time that this agglutination was
one of the aids against bacterial invasion, but it was not supported
by proof until Bull showed that this agglutination is a very prompt
reaction of the body, and that the bacteria are agglutinated, en-
gulfed by white corpuscles, and destroyed in a very short time, so
short a time that it had therefore been missed entirely by other


investigators. If live tj^phoid bacteria are injected into the blood
of an animal which has had typhoid fever, blood drawn one to two
minutes later from the heart or other organs will be found to con-
tain agglutinated clumps of bacteria and white corpuscles which
are already gorged with bacteria, often dozens in a single white
corpuscle. The reason this agglutination was not observed by
earlier investigators in such experiments was that they looked too
late, after the bacteria had been agglutinated and the white cor-
puscles had already destroyed most of them. Another surprising
thing is the strength of this antibody, the agglutinin. A horse in-
jected with typhoid bacteria, until he has become immune to
typhoid, may accumulate a very powerful agglutinin. An agglu-
tinin recently tested at Eockefeller Institute was so strong that one
drop of such horse blood agglutinated many billions of typhoid
bacteria, all that could be grown on four agar tubes.

In some cases these agglutinating substances work in such a
way that the collected clumps of bacteria are large enough to be seen
with the naked eye. If a horse has glanders, his blood-serum con-
tains substances which will clump or agglutinate glanders bacteria
when they are added to the horse's serum in a test tube. The
clumped bacteria are gathered together into a little rounded ball in
the bottom of the test tube, not at all in the way gravity would
cause them to settle. Usually, too, the rate at which they are so
precipitated is very much quicker than in the case of gravity. It
is thought that these precipitating substances are really the same as
the agglutinins, and that they act in the same way in the body, but
differ only in that they are demonstrated better in test tubes than
by the microscope.

Antitoxins. — The antitoxins are another very important class
of antibodies. They differ from all we have discussed in that they
do not affect the bacteria directly, but simply neutralize the poisons
(toxins) which the bacteria make; therefore, antitoxins. In a few
diseases, such as diphtheria, antitoxins are the most important aids
in overcoming the disease. Even when the bacteria are quite local-
ized and not distributed generally through the body, the toxins
formed by the bacteria may be rapidly distributed to all parts of
the body. For example, in diphtheria (Fig. 7), the organisms are
usually located in small patches in the throat, but the poisons these
bacteria make are absorbed by the blood and distributed to all parts


of the body; and we have as a result general irritation and dis-
turbance of many different parts of the body : headache, backache,
nausea, fever, as well as the sore throat one would naturally expect.
If a person is to recover from diphtheria, he must not only kill ofE
the diphtheria organisms in his bod}^, but he must also neutralize
or make ineffective the poisons they have formed. Antitoxins are
the most important protective agents or antibodies against diph-
theria and tetanus (lockjaw) and probably against the ga:s gangrene
bacillus also.

It is not thought that any one of the antibodies works singly or
exclusively in any disease. The serum contains more than one anti-
body, usually ; for example, while antitoxin is the most helpful agent
in aiding against diphtheria, the serum has at the same time some
bactericidal power, and the white corpuscles are also helping to
destroy the organisms. One of the hottest arguments in the history
of bacteriology was about the relative importance of these protec-
tive substances. Metchnikoff, working on tuberculosis, where pha-
gocytosis is the most important protective factor, claimed that re-
covery from disease was due to the action of white corpuscles.
Behring, working on diphtheria, claimed that recovery was due to
the action of the antitoxin. Each worker verified his own findings,
Metchnikoff for tuberculosis, and Behring for diphtheria, and pre-
sented still stronger arguments for his own side. If each had
worked with the other's material, he would have seen at once that
the other was also right. It was another case of the two Imights
and the two sides of the shield.

Immunity Following Disease. — The antibodies which are
formed by our bodies to protect us against invading bacteria are
usually produced in excess of what is actually necessary, and so they
may be found in the body a long time after the bacteria have all
disappeared. This is illustrated by the following diagram (Fig. 52).

The organisms causing a given disease enter the body and begin
to develop at the time represented by a. The body reaction begins
a short time afterward at &. The multiplication of the bacteria
and the increase in antisubstances are represented by the rising
lines a-c and h-d respectively. These two processes run a race, as
it were, and finally at c the antisubstances begin to be found in
excess, and this overproduction continues for a time to d; but from c
the bacteria have been decreasing and, finally, there comes a time.



e, when there are none of them left in the body. The antisub-
stances, however, may persist for some time: weeks, years, or
throughout life. They usually persist a long time after smallpox,
but a very short time after common colds, etc. The time from
e to f represents the time between the end of one attack and the
pojnt at which the individual might come down with another attack
of the same disease. In other words, e to f represents the immune
period following the recovery from a given disease.


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Fig. 52. — Diagram with a black line representing the development of bacteria in
disease, and a broken line representing the lormation of protective substances (white
porpuscles, antibodies). A to B represents the incubation period; EtoF represents the
immune period following recovery. (See p. 199.)

" Natural Immunity." — Sometimes a person's blood contains
some of these antisubstances or immune bodies, even though there
is no record of his having had the diseases in question. We some-
times speak of these people as naturally immune; that may be the
correct explanation, but it is very possible many of these " naturally
immune " people have really had an earlier attack of disease. There
are so many cases that are difficult to diagnose — ^non-typical cases —
as well as so many slight cases which may not demand the services
of a physician, that, we can never be sure how many of these
naturally immune people are really "missed cases."

In a few cases it is quite possible that "natural immunity"
may be related to the illness of the mother a short time before the
birth of the child ; in such cases the child may have had the disease


at the same time, or antibodies in the blood of the mother may have
been transferred to the child.

Other Types of Immunity. — Other types of immunity have
been described, such as racial and age immunities; negroes seem
less susceptible to yellow fever, children are more susceptible to
whooping cough, measles, or scarlet fever than adults (Fig. 53).
Sometimes racial immunity resolves itself into tolerance, and people
who think themselves immune to malaria are sometimes surprised
when the organisms are shown to be present in their blood. This
means that they are not really immune to the disease in question,

necrccLUf. i-n si^sr o p tihillis/ tff di.nfiirhfl.ri'.rx.

,^0^0 so "io 7.5 %

Fig. 53. — Diagram showing relative susceptibility of children and adults to diphtheria.
(From data in Health News)

but that they can tolerate the organisms. The relative immunity of
adults is often traced to " missed " or forgotten cases in childhood ;
children, too, come into closer contact with each other and are less
particular about handling things in a sanitary way, which also helps
account for the so-called partial " immunity of adults " to chil-
dren's diseases : so that all statements regarding immunity must
be weighed carefully before acceptance. Eacial or other predisposi-
tion to disease often resolves itself into increased opportunities for
infection, lessened resistance because of unsanitary homes or in-
sufficient food, etc.

Predisposing Factors. — Hunger, worry, alcoholic excess, over-
work, and overexposure are predisposing factors to disease; for ex-


ample, chickens are quite immune to tetanus, but it has been shown
by experiment that if a chicken is chilled, it succumbs to the in-
oculation of a small amount that otherwise would not affect it.


i In the preceding paragraphs we have spoken as if recovery al-
ways followed an attack of any disease — as if the white corpuscles
and the antibodies always increased at a sufficiently rapid rate to
prevent a deadly accumulation of bacteria and their toxins. Un-
fortunately, this is not true, and bacteria and their irritating prod-
ucts often multiply much more rapidly than the body can provide
protection by the formation of extra white corpuscles, antitoxins,
agglutinins, etc.

If, in our diagram, the line h-d never crossed the line a^c, the
bacteria would continue to multiply indefinitely, and death would
finally ensue. The length and severity of the illness would depend
upon how nearly the reaction or antibody line approached and fol-
lowed the bacteria line.

Chronic cases belong here; their body reactions always lagging
behind what is necessary to destroy all the bacteria.

Methods of Aiding the Individual. — It is now known that it
is possible to help the individuals who are too slow in forming these
protecting substances. "We can do it in three different ways: (1)
by giving them drugs or chemical agents which will kill the bac-
teria; (2) by stimulating the body cells to form the antisubstances
more abundantly; and (3) by giving the individual antisubstances
made in the body of another animal. We will discuss these three
methods separately.

Chemical Agents. — We are somewhat limited in the means we
can employ in the first way, for while there are many chemical
agents which could be used to kill the bacteria, there are not many
that could be used in sufficient strength without destroying the sur-
rounding tissues or irritating them so that they do not heal properly.
For example, strong acids cannot be used to disinfect wounds ; and
while such irritating chemicals as carbolic acid and turpentine are
sometimes used, they are used very sparingly or in very weak dilu-
tions. Eadium is another chemical agent which has serious attend-
ing dangers, as shown by the " radium burns " experienced by doc-
tors and radium handlers. These " burns " often refuse to heal.



even with the best treatment science affords. It is, therefore, con
ceivable that the radium treatment of diseased tissue {e.g., cancer
might injure the body cells before it affected the cause of tha dis-
ease. Below are listed the diseases most commonly treated by drugs
or chemicals:


Drug or chemical







A trade name for an arsenic-

Aniline dyes (gentian violet,
methylene blue)

benzol compound. Other
related drugs are in use for
advanced or severe cases

See table p. 189 for iodine,
alcohol, and other chemicals

Stimulating Body Reactions by Killed Organisms, — There
are several ways of stimulating the body cells to form protective
antibodies; these methods are all alike in that they use dis-
ease organisms which are greatly weakened or killed before they are
injected into the human body. In typhoid, for example, a known
amount of killed typhoid bacteria is injected into the flesh, usually
about 1 or 2 c.c, containing usually one-half to two billion bac-
teria. These bacterial substances are absorbed by the blood, and
stimulate the formation of the same antibodies as would typhoid
entering the body in food, water, etc. Usually three such injections
are given (at intervals of a few days) to make sure that the indi-
vidual forms enough antibodies to last for some time, usually two
to three years at least. Eecently, in the United States army a spe-
cial glycerin combination of three disease organisms has been given,
all in one injection, and with good results (see pp. 211 and 338).

Live organisms have been advocated for typhoid protection, but
since typhoid may persist in the intestine and make people " typhoid
carriers," this seems a very unwise procedure.

Protection by Weakened Organisms. — The earliest use of
weakened organisms to prevent disease was in connection with
smallpox, which was formerly very common; as late as 1750-1780,
in England, France and Italy, less than ten people in every hun-
dred escaped smallpox. Lady Mary Wortley Montagu, in 1718,


introduced into England, after trial in her own family, a method
she found in practice in Turkey. Pus from an eruption on a
"light case" was inoculated into the blood of a person who had
not had smallpox, thus making it quite probable (though not at all
certain) that the inoculated person would have a similarly light
case. This practice was quite generally adopted in the United
States as well as England, and as late as our own Civil War was
used to prevent smallpox. The people of Eichmond, by a house-to-
house canvass, were besought to have their children inoculated ; the
scabs were collected and used to inoculate soldiers in the Confed-
erate army.

A better method of securing weaker smallpox organisms was
even at that time in use in England. Jesty, a farmer, and Jenner,
a physician, knowing the belief of dairy workers that people who
had cowpox did not take smallpox, performed experiments which
proved the accuracy of such beliefs. Jesty inoculated his wife and
two children with cowpox successfully. Jenner tested more directly
whether cowpox could protect against smallpox by inoculating with
smallpox pus ten people who had had cowpox. ISTot one contracted
smallpox, though twenty to fifty years had passed since five of the
number had had cowpox. Jenner added one more experiment, in-
oculating a boy with pus from a dairymaid who, through a cut in
her hand, had contracted cowpox from a cow she milked. This
cow pus " took " ; twice afterward Jenner inoculated the boy with
smallpox pus, but the boy was immune. The material taken from
the cow was called vaccine {vacca, a cow), and the process, vaccina-
tion. Inoculation of smallpox pus from human beings soon decreased
as vaccination was very much safer, and gave a much milder form
of the disease, because the organisms of smallpox had been weak-
ened by their period of growth in the cow.^ About forty years
afterward (1840) the newer method had so gained in favor, that
the English government forbade immunizing people by small-
pox pus.

Other Methods of Attenuating Organisms. — Organisms that
cause disease may be attenuated or weakened in other ways besides
growing them in less susceptible animals. If bacteria are grown in

* There is little doubt that cowpox is really a forin of smallpox con-
traeted bv cows from Iniman beings.


the presence of weak chemicals, subjected to too high or too low a
temperature, dried, or simply allowed to grow old, they may be-
come similarly attenuated. Pasteur used drying to attenuate the
rabies organisms which are found in the brain and spinal cord of
rabid animals. The methods generally used to-day are practically
his methods. The spinal cord of a rabid animal is cut into little
segments, and the pieces are dried to various degrees of dryness. The
pieces dried longest contain, of course, the weakest organisms. The
weakest segments are ground up into a fine emulsion and injected
into the body of the person who has been bitten. His body cells
react to those weak organisms, forming the r.ecessary antibodies.
This is repeated with' stronger and stronger organisms (cord seg-
ments dried for shorter periods of time), until almost full strength
organisms are given — dried for but three days, or even but one

Rabies organisms develop slowly; the repeated injections of or-
ganisms of increasing virulence call forth greater and greater num-
bers of antibodies, until the body is fully protected against all the
results that could have come from the organisms left in the body
when bitten by the dog. It is interesting to know Pasteur tried
this treatment on fifty dogs with success, but even then could not
by the laws of France try it on a human being. Finally he was
allowed to treat an unfortunate individual for whom there seemed
no hope, as he was badly bitten — in fourteen places — and vindicated
his theory.

The Term " Vaccine." — The term vaccine, as we have seen,
was first used for live but weakened organisms obtained from a
living animal^ the cow. Most vaccines, as the term is now used,
are not produced in living animals at all, but are grown in tubes
or flasks of broth in the laboratory; in treatment, some of these
broth growths or cultures are weakened by chemicals, unfavorable
temperatures, etc., but most of them are actually killed before they
are used.

Killed Organisms. — For vaccines made of these killed bacteria,
some authorities use the word tacterin, reserving vaccine for living
organisms. This distinction, however, is not generally made, and
the use of the term vaccine for the killed cultures so widely used
in the recent European war will make it impossible ever to restrict
the word vaccine to its original meaning.


The bacteria used in making all vaccines are taken originally
from disieased tissues and kept alive on such media as broth and
gelatin. Sometimes they lose their virulence in long-continued cul-
tivation on artificial media, but that does not always happen; for
iiLstance, the strain of diphtheria now in use in almost all parts of
tlJe world for making antitoxins was isolated years ago by the New
York City Board of Health, and it seems even mare virulent than
when originally isolated.

There are various types or varieties of most disease organisms.
The vaccine provided by any laboratory is often not made from the
special variety infecting a given individual, and, therefore, not quite
so helpful to him as if made from his own particular type. It can
be secured by taking material (bluod, pus, etc.) from the infected
area and getting from it the organism responsible for the trouble.
This organism may then be grown in broth, etc., and used as a
vaccine. Such vaccines are called autogenous vaccines. In serious
or quickly developing illness there is not time to wait for the
making of autogenous vaccines, as it takes at least two to four
days ; but it is often done in treating slow or chronic diseases, such
as persistent boils, especially if the patient does not respond to the
types of vaccine in general use.

Dosage. — The dosage varies greatly, depending upon the phy-
sician's diagnosis, the period through which the doses are given,
etc. The following figures indicate the wide range: typhoid, 2
million to 10 billion; influenza, 10 to 500 million; streptococcus, 5
to 500 million; staphjdococcus (for boils, etc.), 100 to 1000 million.

Antitoxins. — Some bacteria make large amounts of toxins
which, being soluble, are found in the broth in which the bacteria
are grown. If this broth is filtered, the material passing through
the filter (the filtrate) contains these soluble toxins. If this toxin-
containing filtrate is used for inoeiilation the person or animal reacts,
forming antibodies about as he would if the bacteria had not been fil-
tered out.^ The antibodies thus formed are called antitoxins.

The most recent method of preventing diphtheria in young
children is based upon the stimulation of body reactions by such

^ This is, whenever possible, a preferable method, as it means injecting
less foreign material. Foreign material is always irritating, and even
sterile substances, such as white of egg, not in themselves poisonous, may
cause irritation, abscesses, fever, and even death when injected into animals
in appropriate amounts and at certain intervals.


toxins. They are now inoculated with a modified diphtheria toxin
to cause them to produce sufficient antitoxin to protect tliem
against diphtheria during the susceptible jDeriod of childhood.

Even in diseases contracted naturally we do not, unfortunately,
always react with sufficient promptness to prevent serious illness or
death. It often happens, also, that many individuals do not re-
spond sufficiently even when they are also stimulated by such sub-
stances as vaccines and toxins. Such cases may be aided b}' giving
them the reacting substances formed by another person or animal
and present in the blood of that person or animal (Fig. 54), In
the recent infantile paralysis epidemic an attempt (on a small
scale) was made to protect affected children by injecting blood
from persons who had recovered from infantile paralysis.

It is difficult to secure sufficient amounts of such immune blood,
and, when possible, animals are substituted. Horses are commonly
used for securing such substances, as they are clean animals, free
from most of the diseases that might affect man ; and because it is
possible to draw at one time sufficient blood — ^usually eight to twelve
quarts — to make it worth while commercially. Antitoxins for diph-

Online LibraryJean BroadhurstHome and community hygiene; a text-book of personal and public health → online text (page 19 of 38)