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This article was published in 1939
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INSTITUTE OF INSPECTORS OF STOCK OF N.S.W. YEAR BOOK.

IMMUNITY AND DISEASE

J. R. STEWART. B.V.Sc.

People in professions dealing with life in any of its forms frequently contact diseases, and in the occupation of stock inspection we come closely in touch with their various manifestations. We talk of infection and resistance and use words which often to us are of parrot-like significance—scientific journals sometimes bewilder us with terms hard to understand and difficult to remember. So I thought to-day I would give you an outline of the various reactions which develop in the production of immunity and in the response of the body to disease.

The mechanism of resistance is complicated. In the study of this problem the blood serum has been most consistently investigated, and a number of names have been invented to describe the phenomena observed and the substances produced.

An ANTIGEN is any substance which, when introduced unchanged into the tissues of an animal, causes the production of a specific opposing or reacting material called an "antibody."

An antibody is any substance which makes its appearance in the serum in response to the stimulus provided by the antigen, and when brought in contact with that antigen reacts specifically in some observable manner.

Antibodies are divided into different classes according to what reaction they produce, "in" being placed behind the terms to signify the action. For instance, an antibody which dissolves or lyses is termed a lysin. Now if the particular antibody dissolves blood it is called a hemolysin, so we have "bacterio lysins." An antibody which gives rise to agglutination is known as agglutinin.

PRECIPITIN reaction: This is a chemical reaction of a colloidal nature. When the antigen is brought into contact with the antibody in suitable dilutions or concentrations, a cloudiness appears in the otherwise clear solutions, and in due course a precipitate settles out. The classical example is when white of egg is injected on several occasions into a rabbit and then the rabbit's serum is obtained and placed in a test tube and a few drops of egg albumen is introduced to the serum—a precipitate develops. Its practical application is to determine adulterations in foodstuff. e.g. horse meat in sausages.

AGGLUTINATION reaction: This reaction occurs when any foreign cells, such as yeasts, blood cells, bacteria, etc., are subjected to the action of serum from an animal whose tissues have been invaded by cells of the same type, such as occurs in contagious abortion. This differs from the precipitin reaction in that it is not colloidal but affects part of the structure of organised cells. The practical application here is the abortion test, typhoid test, B.W.D. test.

LYSINS. Lytle reaction: When red blood corpuscles, say of a sheep, have been freed from the serum by suitable washing and are injected into a rabbit and this operation repeated several times, and if the red blood corpuscles of the sheep are then brought in contact with that particular rabbit's serum, the red corpuscles will be ruptured and the hemoglobin will turn the solution red. This phenomenon is made use of in the reaction known as the "complement fixation reaction" and is used classically in humans to detect syphilis, and in veterinary practice to determine pleuro-pneumonia.

OPSONINS: These are described as products occurring in normal serum, acting on a variety of bacteria and rendering them liable to the phagositic action of leucocytes. This is made use of in determining the "opsonic index" (or ability to envelope) of white corpuscles in relation to certain disease microbes.

AGRESSINS are bacterial products which interfere with the defence mechanisms of the host in its fight against a particular disease. Certain organisms are fatal if a sufficiently large dose is given: if a dose too small to kill is given, and if there is added to it a suitable agressin, that dose will now kill: or if a dose of organisms which would slowly kill has added to it some suitable agressin, it will kill the animal rapidly, yet the injections of the agressins of a certain disease alone create an immunity which is far more effective than that produced by the inoculation of bacteria of that disease. In Blackleg agressin we have the application of this principle.

TOXINS are the poisonous products of bacteria, some are created by the organisms whilst living and are free in the fluid in which the organisms are growing; these are called exotoxins. Others are only developed through their liberation from the inside of the microbic cells on the death of the microbes, and are called endotoxins. Many diseases owe their significance to toxins, for instance, botulism and tetanus.

TOXOID is a chemical product allied to toxin, and is usually created from the toxin; it will absorb antibodies. Toxoid is of great significance in the standardisation of antitoxic sera. Toxoid has now found a practical application in the production of tetanus toxoid and many other products incapable of producing disease, but able to induce in the host a strong and lasting immunity.

THE TOXIN-ANTITOXIN REACTION. When you purchase some anti-tetanic serum, you see it contains a certain number of units. The standardisation of the strength of this, as of other biological products is commonly done by the toxin-antitoxin reaction by injecting varying dosages into laboratory test animals, such as mice, rats and guinea pigs.

The reaction is performed by the following method: The toxin is produced and its strength determined against a standard antitoxin which has been previously prepared, carefully standardised and carefully preserved. Then the anti-toxin which it is desired to determine the strength of is then tested against the same toxin, For example, if 1 c. of the standard antitoxin contains 100 antitoxic units, and if I c. of the toxin neutralises 1 c. of the standard antitoxin and also 1 c. of the antitoxin which it is desired to determine the unitage is similarly neutralised by 1 c. of the toxin, then the test antitoxin contains 100 antitoxic units in 1 c.

ANAPHYLACTIC and ALLERGIC reactions: Allergic reactions, in simple language, means hypersensitiveness resulting from previous reactions with certain protein derivatives. Common examples of these reactions may be cited in that certain people cannot eat oysters, strawberries, etc.; hay fever is another example, but the one we are particularly interested in is tuberculosis. The tuberculin reaction is an allergy, in this particular case a medium dose only being used, and the allergic or swelling reaction, or temperature reaction, only being evidenced.

Anaphylactic shock is the term used for a very severe allergic reaction, where the patient is prostrated within a short time after the introduction of the protein materials.

NATURAL ANTIBODIES. Antibodies of various kinds, antitoxins, agglutinins, etc., are constantly found in the serum of normal animals. The new-born of a naturally immune mother is endowed with a passive congenital immunity, which is enhanced by antibodies from the colostrum—this is short-lived. Young animals develop antibodies with advancing age. This production is dependent on the activity of what may be popularly termed "an antibody-forming apparatus" in the system, and that this apparatus is capable of forming non-specific antibodies. Antibodies also arise from external stimuli, such as mild and repeated contact or infection.

Antigens may be introduced in the system from the nose, the lungs, the mouth, the alimentary canal. These non-specific antibodies may have an immunising effect against several different varieties of disease, because several varieties of disease may have a certain common group in their make-up which is counteracted by the one antibody.

The word "immunity" has taken a deep hold in popular language, but it would be better replaced by the word "resistance."

Resistance, in terms of disease, may be defined as the reaction of the host in its endeavour to overcome the invading organism or parasite. We might divide immunity as follows:

(1) Innate Immunity.

(2) Acquired immunity:

(a) Active (i) Naturally acquired; (ii) Artificially acquired.

(b) Passive (i) Naturally acquired (congenital); (ii) Artificially acquired.

(1) Innate Immunity: This is of great practical importance in the relation of infective diseases to various species of animals. In nature, for instance, fowls do not generally acquire anthrax, nor sheep pleuro-pneumonia, or tuberculosis.

(2) Acquired Immunity: This is seldom absolute and different degrees and grades of immunity occur in different individuals.

(This diagram is taken from Topley &: Wilson's "Principles of Bacteriology and Immunity").

This diagram may act as representing an infection of the Invasive type associated with a bacteraemia and local lesions. The width of the black wedge-shaped areas at any level may be taken to represent the chance of death and the degree or frequency of bacteraemia, of local lesions, and of latent infections, in a species of animal possessed of approximately the same grade of resistance.

Thus, starting with the completely susceptible, we may assume that all, or almost all, infected individuals will develop an acute fatal bacteraemic infection. Local lesions will be infrequent and minimal when they occur. There will be no latent infections.

Passing to our next arbitrary grade—partial immunity of low degree—we find fatal bacteraemic infections becoming less common, local lesions more frequent and more pronounced, and a small but increasing number of latent infections.

With partial immunity of a medium grade we find bacteraemia and death much less frequent, local lesions common and relatively extensive, and latent infections increasing in frequency.

With partial immunity of a high grade, death no longer occurs, bacteraemia is infrequent, and when it occurs is slight and transient. Local lesions are becoming much less frequent, and when they occur, much less extensive. Latent infections reach a maximum frequency and then begin to decline.

Finally, we reach the ideal of complete or solid immunity. The host is entirely impervious to all attacks of the invader.

With a fully virulent pathogenic microbe invading a highly susceptible host, the microbe wins the battle. When a weak, avirulent microbe invades a highly resistant host, the microbe loses the battle. Between these two extremes we have all the gradations of disease reactions.

Active Naturally Acquired Immunity occurs when an animal suffers from a disease which produces an active and considerable antibody reaction and the host survives the infection.

Active Artificially Induced occurs as a result of a successful vaccination process which produces an active and considerable antibody reaction and the host survives the reaction.

Passive Naturally Acquired. This is congenital or may be a species resistance.

Passive Artificially Acquired by the introduction into the susceptible animal of a serum containing a large amount of antibodies.

In regard to artificially induced immunities, the lay conception appears to consider it something which is developed in an animal as a result of an injection, which stops the animal from dying of a particular disease. This is quite true, but the lay conception goes further: it thinks that this invisible protective force is always in the animal in unchanging quantity and is equal in every animal subjected to the same immunising process. This is quite wrong. Immunity is only relative, no matter how good immunity is it is possible to break that resistance down.

After an attack of disease or inoculation the immunity rapidly increases, it reaches its maximum in about three weeks and then commences to fall fairly rapidly at first, but later more gradually until finally the immunity is so low as not to be able to ward off another infection. When an animal is immunised and kept under ideal conditions the calls on the vitality of that animal are reduced to the minimum and consequently the immune elements in the system disappear at a slower rate than from an animal subject to droughts, breeding and other adverse conditions. In the case of a ewe in lamb, immunity is lost rapidly, particularly in such diseases as entero toxaemia; her system is depleted to provide for the lamb in utero, then the lamb removes from her system, through the colostrum, a considerable quantity of antibodies to protect itself during its early weeks of life: thus such a sheep would become susceptible to infection in a much shorter period than a similarly non-nursing ewe. High resistance or a strong state of immunity is maintained in an immune animal by repeated injections at not too distance intervals.

Phagositosis is the phenomenon of the leutocytes, or white corpuscles, enveloping and probably digesting certain bacteria; this is a common process of repair in disease.

We will now consider the various uses made of the above reactions in relation to our disease problems. As just mentioned, the tuberculin reaction, is allergic, as is the mallein reaction for the detection of glanders.

VACCINES are suspensions of bacteria in a suitable liquid and are used for the preventive or curative treatment of their specific type of disease. Their virtue is dependent upon the production in the system of any, all, or several of the antibodies described above. They may be dead vaccines, and in this case are often called bacterins, or they may be living vaccines; in this case they are usually modified in some manner to reduce the risk of fatal or undesirable results. There are a great variety of vaccines in use, the best being anthrax vaccines.

Virus is the living diaease, either in natural form or in suitable culture medium or diluent, of an organism so small that it will pass through fitters which hold back visible organisms.

Cow pox, fowl pox and scabby mouth are virus diseases and are prevented by means of suitable preparations of the appropriate virus. These are weakened strains of living pox virus and are usually grown and maintained upon animals of the same species to which they belong.

Antitoxins, toxicultures, etc., are products used for immunising against diseases, prepared by changing the toxins of certain pathogenic cultures into toxoids or modified toxins. Such products contain the organisms which produced the toxin, and the modification is commonly brought about by the addition of appropriate amounts of formalin. In black disease and pulpy kidney vaccines we have examples of this reaction.

Blackleg is prevented by means of blackleg agressin, anatoxins and modified blackleg organisms in the form of pellets and threads.

 


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