It has been proved by experiment that, against many of those chemical substances, an artificial immunity may be given to the protozoa by accustoming them gradually. Very diluted solutions are added at first to the medium in which they live and, by gradually concentrating those solutions, an artificial immunity is conferred; the negative chimiotaxis becomes positive, allowing the protozoa to absorb and digest the poison, now become a food.
Habit is therefore the fundamental condition of artificial immunity; it must be that also of immunity naturally acquired. Having accidentally digested enfeebled microbes or having suffered an attack of disease, the unicellular being becomes accustomed to a stronger virus and becomes immune against it. The fact that so many unicellular beings have become thus accustomed is therefore connected with their sensitiveness and their digestion. Accordingly, sensitiveness, habit, and digestion are the fundamental factors of the mechanism of immunity in protozoa; this immunity thus indisputably belongs to the category of purely cellular phenomena.
Having arrived at this conclusion, Metchnikoff thought that the same mechanism of immunity must be found in other primitive and analogous cells, such as the phagocytes of multicellular beings. This was proved by a whole series of observations and by the fact that the immunity of higher animals is connected with an intense phagocytosis. In fact, as he ascended the scale of beings and studied their natural and artificial immunity, he ascertained that, in all of them, the essence of immunity, masked by the complexity of the organism, reduced itself to the phagocytes becoming accustomed to noxious agents. The mechanism of immunity in protozoa could therefore really be compared with that of immunity in multicellular beings.
Becoming accustomed and becoming immune are phenomena of a general order, for they can be manifested not only by animals, but also by plants. They, too, have to defend themselves against numerous diseases. Lower vegetables, such as myxomycetes (beings which stand on the limit between the animal and vegetable kingdoms), have an amœboid phase, in which they are but a simple heap of formless protoplasm. During that stage of their life, myxomycete behave towards noxious agents exactly in the same way as unicellular beings and, like them, acquire immunity by becoming gradually accustomed.
In higher vegetables, the mechanism is different because of their structure. The cells of nearly all plants are immobilised by rigid membranes; therefore they cannot surround their prey, but protect themselves by the production of tough membranes (cicatrisation) and by the secretion of various juices. Certain of these juices (gums and resins) become solid when exposed to the air and constitute a sort of natural (dressing); others (essences) are antiseptic. The secretion of these cellular juices in plants is therefore a powerful means of defence. This defence is due to the extreme sensitiveness of the protoplasma of vegetable cells: they react against irritation by a defensive secretion. Vegetables, as well as unicellular beings, can accustom themselves or become artificially accustomed to noxious influences and acquire immunity.
As to animals, Metchnikoff had already proved long ago that they defend themselves against morbid agents by phagocytosis, i.e. by intracellular digestion. It is always to be found in cases of immunity and is indispensable to it, on the same grounds as in unicellular beings. The organism of multicellular animals possesses various cells which play the part of phagocytes. There are some in the blood and humors, as also in the divers organs and in the tissues. These phagocytes are either mobile—leucocytes, or fixed—tissue-cells. However, all those cells may be classed into two principal groups: the microphages and the macrophages. Both categories of cells are capable of digesting microbes, but it is chiefly done by the microphages, whilst macrophages more especially digest figured elements (cells) of animal origin and poisons. It may be said that the microphages are vegetarians whilst the macrophages are chiefly carnivorous.
What, then, is the mechanism of phagocytic digestion?
Intracellular digestion by phagocytes is accomplished by means of digestive ferments, similar to those of our own digestive organs. “In both cases,” says Metchnikoff, “a diastasic action is due to soluble ferments produced by living elements. In intracellular digestion, the diastases digest within the cells, whereas in extracellular digestion the phenomenon takes place outside the cells, in the cavity of the gastro-intestinal tube.”
Only gradually has intracellular digestion given place to the digestion by secreted juices. The link between these two modes is to be found in certain transparent Invertebrates, such as the floating mollusc Phyllirhoë. The nourishment is first digested in the cavity of the digestive tube by secreted juices, and its treatment is completed within the amœboid cells of the cæcum.
In higher animals, the digestion of food is due to several digestive ferments (rennet, pepsin, trypsin, enterokinase, etc.) produced by divers organs (stomach, pancreas, intestines). The phagocytes also manufacture several digestive ferments; their principal digestive juice is a soluble ferment of the trypsin category, to which Metchnikoff gave the name of cytase.[25]