Phagocyte

“ Sometimes, however, the invading microbes come in, not in companies but in platoons, innumerable as Xerxes' Persians, and then "e'en Roderick's best are backward borne," and we die. For our life is the prize of the combat in these novel lists which science has revealed to our view through the microscope, and health is but the token of the triumphant victory of the phagocyte over the microbe. ”

“ In that article he expounded the phagocyte theory of immunity. [209] Among concrete examples of its application, he quoted the indications concerning the evolution of an infectious disease provided by the quantity of leucocytes in the blood, and the process employed by certain surgeons to diminish the danger of infection during an operation: just as, in case of an enemy menace, the Government mobilise an army, certain surgeons employ divers means to attract an army of phagocytes and to stimulate their activity in case any microbes should penetrate into the wound. ”

“ The mechanism of destruction of a bacterium once it has been taken up by a phagocyte is probably, just as in the instance of dead cellular material, one of intracellular digestion. The bacterium before being engulfed is probably inert in most instances, though it may yet prove too strong for the phagocyte. The next stage we can trace is the formation of a vacuole around the organism, or, if the latter be large, around a part of the organism, and the part thus surrounded quickly shows signs of destruction. ”

“ The bacteria elaborate a chemical substance which attracts the phagocyte, and this is termed "positive chemiotaxis."80 But it may occur that the chemical substance produced by the bacteria may have an opposite, or repellent, effect upon the leucocytes, in which case we have "negative chemiotaxis."81 It is not to be wondered at that such a theory of immunity based upon microscopical observations, should at first have been widely accepted, and there can be no doubt that Metschnikoff has collected a considerable mass of evidence in support of a theory of phagocytosis. ”

“ The extruded microgametes, if they do not break away as already described, may continue to move for an hour, or even longer—that is, if the flagellated body be not engulfed by a phagocyte, an occurrence very frequently witnessed. ”

“ Phagedena, Phagedæna, faj-e-dē′na, n. a sloughing ulcer, hospital gangrene.—adjs. Phagedē′nic, Phagedæ′nic. [Gr. phagein, to eat.]
Phagocyte, fag′o-sīt, n. a white or colourless blood-corpuscle—also called leucocyte—an active amœboid cell, which engulfs both nutritive and harmful particles.—adjs. Phagocyt′ic, -al.—ns. ”

“ If the bacterial theory of infection, constantly threatening life by such numerous pathogenic varieties of infecting organisms, must be looked upon as a gloomy one, the anti-bacterial Phagocyte Theory of Metschnikoff, professor of zoology in Odessa, is adapted to make one feel more comfortable, inasmuch as it brings into view the possibility of an antagonism to these infecting organisms, and explains the method of nature's cures. ”

“ This phagocytal action of certain cells of the body is held by Metchnikoff and his followers to have an important bearing on the pathology of immunity. Phagocytes act as scavengers in ridding the body of noxious particles, and more especially of harmful bacteria.
A further application of the facts of chemiotaxis and phagocytosis has been made by Metchnikoff to the case of Inflammation. It is well known that many attempts to define the process of inflammation have been made from time to time, all of them more or less unsatisfactory. ”

“ That phagocytes can paralyse, kill and digest many microorganisms is the main fact in Metchnikoff’s theory of the nature of immunity. The reaction may be readily studied by injecting a small quantity of a fluid culture of some mildly pathogenic organism into the peritoneal cavity of an animal, and in the course of an hour or so examining a smear from the surface of the omentum, when an abundance of phagocytes enclosing the organism in different stages of digestion will be found. ”

“ These cells are probably p/mgocytes. A phagocyte is a blood corpuscle that destroys foreign proteid bodies in the blood, or any unhealthy tissue of the body. It is hot probable that the insect phagocytes are the active cause of the destruction of the larval tissues, but they do engulf and digest particles of the degenerating tissues. ”

“ It is a commonplace that different people vary in their susceptibility to the attacks of different organisms, and different species of animals also vary greatly. This “natural immunity” is due partly to the power possessed by the leucocytes or white blood corpuscles of taking into their bodies and digesting or holding in an inert state organisms which reach the blood—phagocytosis,—partly to certain bodies in the blood serum which have a bactericidal action, or whose presence enables the phagocytes to deal more easily with the organisms. ”

“ 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. ”

“ Metchnikoff showed that in animals immune to a given organism phagocytosis is present, whereas in susceptible animals it is deficient or absent. He also showed that the development of artificial immunity is attended by the appearance of phagocytosis; also, when an anti-serum is injected into an animal, the phagocytes which formerly were indifferent might move towards and destroy the bacteria. ”

“ The increased ingestion of bacteria in active immunity would seem to depend upon the presence of immune opsonins in the serum. These, as already explained, are true anti-substances. Thus the apparent increased activity of the leucocytes is due to a preliminary effect of the opsonins on the bacteria. We have no distinct proof that there occurs in active immunity any education of the phagocytes, in Metchnikoff’s sense, that is, any increase of the inherent ingestive or digestive activity of these cells. ”

“ RIDGEON. Phagocytes.
SIR PATRICK. Aye, phagocytes: yes, yes, yes. Well, I heard this theory that the phagocytes eat up the disease germs years ago: long before you came into fashion. Besides, they dont always eat them.
RIDGEON. They do when you butter them with opsonin.
SIR PATRICK. Gammon.
RIDGEON. No: it's not gammon. What it comes to in practice is this. The phagocytes wont eat the microbes unless the microbes are nicely buttered for them. Well, the patient manufactures the butter for himself all right ”

“ Sometimes they pass back into the blood stream and carry the bacteria to various parts of the body for elimination. Not infrequently the white corpuscles die in the contest, and then may accumulate in the form of pus and make their way through the skin to be discharged directly. The battle between these phagocytes and the bacteria goes on vigorously. If in the end the phagocytes prove too strong for the invaders, the bacteria are gradually all destroyed, and the attack is repelled. Under these circumstances the individual commonly knows nothing—of the matter. ”

“ The known mechanisms for this in the body are ameboid cells, especially the phagocytes. It is most probable that these are the chief agents in getting bacteria into the tissues through various free surfaces. The phagocytes engulf bacteria, carry them into the tissues and either destroy them, are destroyed by them, or may disgorge or excrete them free in the tissues or in the blood.
DISSEMINATION OF ORGANISMS.
Dissemination of organisms within the tissues occurs either through the lymph channels or the bloodvessels or both. ”

“ The non-sensitiveness of a cell to a toxic body when brought into immediate relationship cannot, however, be explained further than by saying that the disintegrative changes which underlie symptoms of poisoning are not brought about. Then as regards natural powers of destroying bacteria, phagocytosis aided by chemiotaxis plays a part, and it can be understood that an animal whose phagocytes are attracted by a particular bacterium will have an advantage over one in which this action is absent. ”

“ A healthy eye, or finger, or tooth is not felt; it is nonexistent, as it were. Is it not clear, then, that consciousness of oneself is a sickness?
Apparently I am no longer a phagocyte which quietly, in a businesslike way, devours microbes (microbes with freckled faces and blue temples) ; apparently I am myself a microbe, and she, too, I-330, is a microbe, a wonderful, diabolic microbe! It is quite possible that there are already thousands of such microbes among us, still pretending to be phagocytes, as I pretend. ”

“ 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. ”

“ It may sometimes occur that the poison secreted by a microbe will paralyze and kill the leucocyte, unless care has been taken, by inoculations of virus, at first attenuated and afterward gradually increasing in virulence, to create an immunity in the phagocyte, to make it refractory to the poison and capable of swallowing the toxic bacterium without suffering from it. ”

“ The immunity of many persons from infectious diseases, so far as it is not effected by inoculations, would by analogy be explained on the theory that with such individuals the phagocytes are from the outset so constituted that they at once render harmless any stray bacteria which come within their domain by immediately devouring them. ”

“ Disease-germs, bacteria, or protozoa produce poisons which sometimes are too much for the phagocytes, poisoning them and so getting the upper hand. But, as Metschnikoff showed, the training of the phagocytes by weak doses of the poison of the disease-germ, or by weakened cultures of the disease-germ itself, brings about a power of resistance in the phagocytes to the germ’s poison, and thus makes them capable of attacking the germs and keeping them at bay. ”

“ The phagocytes absorb morbid matter, poisons or microorganisms by enveloping them with their own bodies. It is a hand-to-hand fight, and many of the brave little soldiers are destroyed by the poisons and bacteria which they attack and swallow. What we call pus is made up of the bodies of live and dead phagocytes, disease taints and germs, blood serum, broken-down tissues and cells, in short, the debris of the battlefield. ”

“ In a well-organized, well-developed, and therefore well-protected person the bacilli are overwhelmed by the irruption of phagocytes at the point of entry, and immunity is the result. In one of less protective power they may enter and be carried along by the lymphatics to the lymphatic glands, where they undergo digestion and destruction. ”

“ To this process Metchnikoff gave the name of phagocytosis, and he recognised two forms of phagocytes: (1) the microphages, which are the polymorpho-nuclear leucocytes of the blood; and (2) the macrophages, which include the larger hyaline leucocytes, endothelial cells, and connective-tissue corpuscles. ”

“ Metchnikoff was not content with observing lower animals but wished to study the reaction of the organism of mammals in infectious diseases. At that time, the best-known microbe was the bacillus of anthrax. He therefore chose that for his researches and ascertained that phagocytosis varied with the virulence of the microbes; thus, while phagocytes did [122] not attack virulent bacteria, they attacked and rapidly digested attenuated bacteria. Moreover, he observed a very active phagocytosis in refractory animals and the reverse in sensitive ones. ”

“ Phagocytosis or the destruction of the invading organisms within the leukocytes.
4. Opsonins which render the bacteria more readily taken up by the phagocytes.
5. Enzymes other than complement possibly play a part in the destruction of some pathogenic organisms or their products. This remains to be more definitely established.
6. It is possible that in natural immunity there might be no receptors in the body cells to take up the organisms or their products, or the receptors might be present in certain cells but of a very low chemical affinity, so that combination does not occur. ”

“ The prophylactic effects of inoculation are explained on the theory that by means of this operation the wandering cells are prepared, as it were, for subsequent accidental irruptions of similar pathogenic bacteria, are habituated or compelled thereby to at once devour such organisms when they enter the body spontaneously, and thus to render them harmless. Inoculation would thus be a sort of training or education of the phagocytes. ”