The labors of M. Metchnikoff have made known one of the most curious mechanisms—perhaps the most effective—which Nature employs to protect the organism against the invasion and ravages of microbes. We are only beginning to learn the means which are provided for our defense against the countless swarms of enemies of this class, some of them exceedingly dangerous, among which we have to live and move. In the first rank of these defenses is phagocytosis. The struggle of the organism against its minute assailants is an image of human wars. The cutaneous or mucous integument, continuous over the whole body, constitutes a kind of fortified inclosure which the microbe can not penetrate, except where some breach has been made. On one side of that wall, in the living city, the phagocytes or leucocytes (white cells) form an immense defensive army in a state of continual mobilization, or, as M. Duclaux would say, an innumerable and vigilant police.
These phagocytes or leucocytes are the nomadic elements of our economy. The animal body may be compared to an organized city in which all the living corpuscles, all the cellular elements, are sedentary, each having its place and staying there. Hence the comparison, often made, with the stones of a building, which is not exact, however, because these vital elements grow and increase, enlarging the structure without change of arrangement, while the stones do not. The growth and nutrition of these anatomical elements, it should be added, are carried on exclusively at the expense of liquid matters. Nothing solid can enter them or come out from them.
An exception to these two fundamental rules is found in the single case of the leucocytes or white globules of the blood. They have no fixed or determined place in the organism. Besides being carried passively by the flow of the blood in a perpetual circulation along with the red corpuscles, they possess a motion of their own. They can swim in the current that carries them, fix themselves to the walls, and travel in a sort of creeping way, which has been called the amœboid motion.
They are also exceptions to the second law, according to which living cells can dispose only of liquefied matters. All solid bodies that pass within reach of the leucocytes are seized and incorporated by them, provided they are small or inert enough to be enveloped. The nature of the body is of little import. Whatever it may be, it is swallowed and quickly inclosed within the mass of the leucocyte and submitted to the dissolving action of its juices—or, in a way, eaten. Hence the names “phagocyte,” or devouring cell, given to the enveloping white globule, and “phagocytosis” to the process. No other element of the organism, or hardly any other, possesses this singular faculty of seizure and swallowing (inglobement).
All the other characteristics of the white globules flow from these two of mobility and phagocytism, the significance of which has been set in a clear light by M. Metchnikoff. These characteristics are the attributes of the most primitive types of animal life. They appertain to cells not yet differentiated, to the unicellular organisms which occupy the first stages of life. They translate the vital energy of elements still independent and isolated, without definite place in the social organization and as yet without special high function, but for that very reason better adapted to the needs of the simplest animality. Their voracity is useful for the preservation of the social organism. By eliminating old, exhausted, diseased cells they rejuvenate the structure and prepare the way for new generations. And when the fecundity of these is exhausted the leucocytes come in to occupy the vacated situations, and conduct the organism thus patched up through a senile degeneracy to natural death.
The leucocytes, white globules, or phagocytes, by virtue of their mobility, are found everywhere—in the blood, in all the organs, and in all parts of the body—but are perhaps most abundant in the blood. The study of them proceeds slowly, and we are still engaged in distinguishing the varieties among them. The most abundant and best known of them—those which answer most closely the description we have given—are those called the polynuclear, neutrophilous leucocytes. They are colored with neutral hues, and have a nucleus like a rolled-up scroll in structure. Other varieties—the eosinophiles, lymphocytes, etc.—are less mobile and have still less marked phagocytic properties.
The roll-call of the phagocytic army would be a long task. The phagocytes are numerous in the sanguineous fluid, but are still six hundred and fifty times less so than the red corpuscles. They are almost as numerous in the lymph and the conjunctival tissue, where, besides occurring in their normal condition, they sport into a variety which appears to have abandoned its migratory habit, for a time at least, and into a giant variety one hundred times larger than the ordinary leucocytes, which M. Ranvier calls clasmatocytes. They are further found in such tissues as the skin and the mucous membrane, where, notwithstanding the cells are so crowded, they make their way into the intestine, and, by a sort of diapedesis (passage through the pores or interstices) called the phenomenon of Stoehr, toward all the free surfaces, whither exterior soluble substances invite them. As they go they destroy the microbes which, advancing in an inverse direction, would invade the organism and provoke an infection of intestinal origin.
The fact that this immense army of phagocytes is always in motion was first clearly recognized by Cohnheim, in 1867. He saw, in inflamed regions, where the vessels are gorged and distended, the white globules thrusting out a prolongation which seemed to pierce the wall, but in reality simply insinuated itself between its elements, and elongating itself, drew its entire body, as it were, through the narrow channel. This emigration, which is produced without making a break, through the pores and interstices of the vascular wall, has been designated diapedesis. It is ordinarily provoked by some foreign body, a pathogenic microbe, for instance, which has introduced itself into the place and spread its irritating secretion or cause of infection there. The phagocytes, attracted from the interior of the vessel, come up and devour the invader. But if they are incapable of dissolving it they bear it away to work their own ruin; they degenerate in their turn, become transformed into globules of pus, and the inflammation results in purulence. The study of the mechanism by means of which the leucocytes traverse the tissues is very interesting.
These remarkable wandering elements are found in all classes of animals, and in all present the same essential characteristics. They are more like free existences than the other cells living in society which compose the bodies of animals, and their history is substantially like that of the naked one-celled organisms. Their various functions and properties are of the highest interest in all departments of physiology. It has been demonstrated, in particular, that the white globules of the blood give rise to the most energetic and most special agencies of living chemistry, to the ferments which determine the coagulation of the blood when drawn from the vessels (coagulating ferment, or thrombosis) and the consumption of sugar (glycolytic ferment), and to numerous diastases. The presence of nuclein in their bodies involves consequences which we are only beginning to perceive.
Behaving like independent beings, the leucocytes or phagocytes perform similar functions with those of the highest animals, feeding, respiring, and reproducing themselves; they move and feel—that is, are impressed by internal excitants. These operations, however, assume with them a character of extreme simplicity. They seem to be the direct result of the physical and chemical properties of the protoplasm that composes them, so that the mysterious side of those vital functions nearly vanishes when we scan them in these their very beginnings. Their respiration is the effect of a sort of affinity between their substance and the vital gas—a chimiotactism directing them toward oxygen. This may be illustrated by forming a microscopic preparation of fresh lymph, imprisoning a few bubbles of air, and sealing it hermetically with paraffin. After two or three hours we can see the leucocytes grouped around the bubbles. When the provision of air is exhausted, several hours afterward, the leucocytes will cease to move and become inert. On inserting a needle, the contact of the air revives them.