Phagocytosis

“ The white corpuscles of the blood are leucocytes. “The work of these cells is to prey upon and take into their substance bacteria and other micro-organisms within the blood and tissues. This destruction of bacteria, and other noxious organisms, has the biological name of phagocytosis.”
Dr. Alonzo Brown in Physician and Surgeon says of phagocytosis:—
“Recently a brilliant theory has been projected into the histological world. ”

“ It was found that the tissues were attacked by phagocytic cells that became enlarged and carried away fragments of the tissue; the cells were subsequently identified as leucocytes or blood-cells. Hence the opinion arose that histolysis is a process of phagocytosis. It has, however, since been found that in other kinds of insects the tissues degenerate and break down without the intervention of phagocytes. It has, moreover, been noticed that even in cases where phagocytosis exists a greater or less extent of degeneration of the tissue may be observed before phagocytosis occurs. ”

“ 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 amboceptors so necessary for the destructive action of the serum are produced by the body cells, particularly the leucocytes. The serum assists in pagocytosis by the action on bacteria of substances called opsonins which are contained in it, and the formation of which can be very greatly stimulated. Again, not all inclusion of bacteria within leucocytes is indicative of phagocytosis; in many cases the bacteria seem to find the best conditions for existence within the leucocytes, and these and not the bacteria are destroyed. ”

“ Undoubtedly the phenomena of racial and species immunity are affected by phagocytosis. But our present knowledge does not justify us in disregarding other possible and contributing agencies. We are still so little informed of even the grosser features of the body's metabolism that it would be premature to deny to it influence on susceptibility to infection. Between the metabolism of birds and mammals there is such wide disparity that an influence could easily be conceived ”

“ Thus he said in his paper to the Odessa Congress:
The theoretical study of Natural History problems (in the largest sense of the word) alone can provide a critical [121] method for the comprehension of truth and lead to a definite conception of life, or at least allow us to approach one.
And yet, until then, the theory of phagocytosis as a curative force of the organism was but a hypothesis, for he had not yet observed spontaneous phagocytosis in diseases and did not know pathogenic microbes. ”

“ In this process there are two factors concerned, viz. the ingestion of bacteria by the cells, and the subsequent intracellular digestion. If either of these is wanting or interfered with, phagocytosis will necessarily fail as a means of defence. As regards the former, leucocytes are guided chiefly by chemiotaxis, i.e. by sensitiveness to chemical substances in their surroundings—a property which is not peculiar to them but is possessed by various unicellular organisms, including motile bacteria. When the cell moves from a less to a greater degree of concentration, i.e. ”

“ On our way back we passed through Berlin, where Metchnikoff wished to see Professor Koch and to show him some interesting specimens of phagocytosis. The great savant received him very coldly. For a long time, while examining specimens of the spleen in relapsing fever, he refused to recognise in them an example of phagocytosis. Though he was at last obliged to bow to evidence, he yet remained unfavourable to the phagocyte theory, and all his assistants followed his example. ”

“ 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. ”

“ 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. ”

“ Phagocytosis is the act by which the leucocytes englobe and dissolve the invading microbe. By its amœboid movement the leucocyte flows around, and envelopes the microbe for which it has a positive chemiotaxis, and then begins the struggle of vitality between the two living germs. If the poison (leucomaine antitoxin,) and digestive ferment (enzyme) of the leucocytes are more deadly to the invading germ, than its ptomaines, toxins and enzymes are to the leucocyte, the white cell comes off the victor, and recovery takes place, but if the converse obtains the triumph is on the side of the microbe. ”

“ It remains to be fully investigated whether they enhance IgG recognition of specific variants of PfEMP1 or other surface antigens that are known to play a role in malaria immunity.
Antibody-mediated phagocytosis of iRBCs is believed to be an important effector mechanism in protection from malaria. Investigations with normal RBCs have demonstrated that monocytes preferentially phagocytose iRBCs compared to uninfected RBCs, and that this preference is potentiated by the binding of IgG to iRBCs [101] . ”

“ 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. ”

“ The serum of the susceptible rabbit, for example, is bactericidal to this organism, whilst the serum of the immune dog is not. In the case of the latter animal the serum contains an opsonin which leads to phagocytosis of the bacillus, and the latter is then destroyed by the leucocytes. It is quite evident that bactericidal action as tested in vitro outside the body does not correspond to the degree of immunity possessed by the animal under natural conditions. ”

“ Not only is there an incursion of lymphocytes into the parts but the connective tissue and endothelial cells in their vicinity revert to their embryonic state and begin the work of phagocytosis. But as a fact they have to deal with neither the effete products of molecular degeneration nor with an inert foreign body, for though virtually strangers cancer cells are by no means inactive. ”

“ 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. ”

“ From a pathological point of view the subject of chemiotaxis must be considered along with that of phagocytosis. Certain free mobile cells within the body, such as blood-leukocytes, as well as others which are fixed, as for instance the endothelium of the hepatic capillaries, have the property of seizing upon some kinds of particulate matter brought within their reach. Within a quarter of an hour after a quantity of cinnabar has been injected into the blood of the frog nearly every particle will be found engulfed by the protoplasm of the leukocytes of the circulating blood. ”

“ Various observers had previously found that the serum of an animal immunized against [v.03 p.0179] a particular bacterium had a special action in bringing about phagocytosis of that organism, and it had been found that this property was retained when the serum was heated at 55° C. It is now generally admitted that at least two distinct classes of substances are concerned in opsonic action, that thermostable immune opsonins are developed as a result of active immunization and these possess the specific properties of anti-substances in general, that is, act only on the corresponding bacterium. ”

“ It is the gathering of soldiers to destroy an invader. This is accomplished partly by means of phagocytosis—actual ingestion of the enemy—and partly by means of chemic substances which the leukocytes produce.
In those diseases in which leukocytosis is the rule the degree of leukocytosis depends upon two factors: the severity of the infection and the resistance of the individual. A well-marked leukocytosis usually indicates good resistance. A mild degree means that the body is not reacting well, or else that the infection is too slight to call forth much resistance. ”

“ 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. ”

“ Active immunity has thus been shown to be associated with the presence of certain anti-substances in the serum. After these substances have disappeared, however, as they always do in the course of time, the animal still possesses immunity for a varying period. This apparently depends upon some alteration in the cells of the body, but its exact nature is not known.
The destruction of bacteria by direct cellular agency both Phagocytosis. in natural and acquired immunity must not be overlooked. ”

“ 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. ”

“ On reaching the vicinity they leave the blood stream and join in the warfare—many performing their function of phagocytosis (q.v.) , others falling victims to the toxins. The tissues of the part become disorganized or destroyed, and their place is taken by the mass of warring cellular elements now recognized as pus.
As soon as the fluids and the polymorpho-nuclear leukocytes have succeeded in diminishing the virulence of the micro-organism, the second line of defenders—the large mononuclear leukocytes (fig. 23, Pl. II.) make their appearance at the field of battle in ever increasing numbers. ”

“ They further showed that this substance acted by combining with the organisms and apparently producing some alteration in them; on the other hand it had no direct action on the leucocytes. This opsonin of normal serum is very labile, being rapidly destroyed at 55° C.; that is, a serum heated at this temperature has practically no greater effect in aiding phagocytosis than normal salt solution has. ”

“ The infection begins with elementary bodies or elementary corpuscles which live at first extracellularly. An elementary body is a minute speck of chromatin, apparently devoid of cytoplasm, which can pass through a bacterial filter. It can enter a host cell, but the entry is not a process of phagocytosis.
2. Inside the host cell the elementary body grows in size, and becomes an initial body (fig. 119, a) .
3. A reaction on the part of the host cell results, for nucleolar, plastin substance is extruded from the cell-nucleus and surrounds the parasitic initial body. ”

“ As soon as a leucocyte touches a resisting body it reacts to the contact by applying the largest possible surface to it. It spreads out, becomes thin, stretches itself along, and ceases deforming itself only after it has obtained the maximum of contact. By such mechanism it penetrates objects that offer it any breach and overcomes them. When the foreign body has been disaggregated into fragments, into small enough grains, phagocytosis intervenes and disposes of the remains. In this way the organism sometimes rids itself of splinters of bone that remain in the tissues after a fracture. ”

“ Then, there may be more polymorphonuclear leucocytes in the sinuses, and necrotizing foci may be converted into miliary abscesses.
The change in the bronchial lymph glands cannot be considered other than an expression of an aplastic, inflammatory reaction. It finds an analogue especially in diseases like typhoid fever. The most constant picture includes an edematous, hemorrhagic reaction in which there is phagocytosis of sieved-out cells by the scavengers generated within the gland. Where necrosis or suppuration occurs, and this is rare, it may be considered as a complication. ”