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.
In the " seventies " of the 19th century feeling ran somewhat high over the rival doctrines concerning the origin of puscorpuscles, Cohnheim and his school maintaining that they were derived exclusively from the blood, that they were leucocytes which had emigrated through the walls of the vessels and escaped into the surrounding tissue-spaces, while Stricker and his followers, although not denying their origin in part from the blood, traced them, in considerable proportion, to the fixed elements, such as fibrous tissues and endothelia.
It is largely to researches on the bone marrow that we owe our present knowledge of the origin and the classification of the different cellular elements of the blood, both erythrocytes or red corpuscles, and the series of granular leucocytes or white corpuscles.
If the white cells be required, as in local suppurating abscess, general septicaemia, acute pneumonia, &c., there is an active proliferation of the myelocytes to form the polymorpho-nuclear leucocytes, so that we have in this condition a leucoblastic transformation of the fatty marrow.
Absorption of this infarcted zone is carried on by means of leucocytes and other phagocytic cells, and by new blood-vessels.
The polymorpho-nuclear leucocytes are seen in great numbers in the blood vessels.
To replace this cellular destruction there has been a demand for reinforcements on the home centres of the polymorpho-nuclear leucocytes - the bone marrow.
Leber experimented with several chemical compounds to find what reaction they had on these cells; by using fine glass tubes sealed at the outer end and containing a chemical substance, and by introducing the open end into the blood vessels he found that the leucocytes were attracted - positive chemiotaxis - by the various compounds of mercury, copper, turpentin, and other substances.
It has been proved that the pyo-genic bacterial toxins, if not too concentrated, will attract the polymorpho-nuclear leucocytes, but if concentrated, may have a repelling influence.
Along with the exuded serum this fills up the breach in the tissues and the whole is rapidly formed into a fibrinous mass due to the disintegration of the polymorphonuclear leucocytes setting free their ferment.
As early as six hours after the injury the polymorpho-nuclear leucocytes are seen passing in large numbers from the dilated and congested blood vessels of the tissues at the margin of the wound into the injured zone, where they carry on an active phagocytosis.
A small cellular area formed by emigrated polymorpho nuclear leucocytes surrounding a central mass of bacteria.
Numerous polymorphonuclear leucocytes and a few mononuclear cells, one of which has taken up a leucocyte into its interior (phagocytosis).
Massart and Bordet, Leber, Metchnikoff and others have studied the phenomenon in leucocytes, with the result that while there is evidence of their being positively chemiotactic to the toxins of many pathogenic microbes, it is also apparent that they are negatively influenced by such substances as lactic acid.
Certain free mobile cells within the body, such as blood-leucocytes, 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 leucocytes of the circulating blood.
104; Buchner, " Chemiotaxis of Leucocytes," Berl.
135; Lowit, " Relationship of Leucocytes to Bacterial Action," Beitr.
Ii.; Marshall Ward, Timber and some of its Diseases (London, 1889); Massart and Bordet, " Irritability of Leucocytes," Journ.
Sicherer, " Chemiotaxis of Leucocytes of Warmblooded Animals outside the Body," Munch.
The white blood-cells, or leucocytes, undergo other changes.
These are undoubtedly the organs which react most strongly to the parasites, and their enlarged condition is to a great extent due to their enhanced activity in elaborating blood-corpuscles and leucocytes to cope with the enemy.
The greater the number of leucocytes that can reach the spot where the invading microbes enter the more quickly can the microbes be destroyed and general infection prevented.
The microbes appear in many cases to attract the leucocytes (positive chemiotaxis), but when very virulent they usually repel the leucocytes (negative chemiotaxis) and excrete toxins which kill the leucocytes.
The irritation caused by the microbes generally is followed by dilatation of the vessels of that part and thus more leucocytes are brought up to the fight.
The toxins produced by microbes, if too weak to destroy the leucocytes, induce them to secrete antitoxins, which not only act as antidotes to the toxins and are injurious to the microbes, but also increase the phagocytic power of the leucocytes (opsonius of Wright).
The vaccine is usually made by sterilizing a virulent culture and the proper dose is ascertained by noting 'the extent to which the power of the leucocytes to envelop and digest the microbes is increased.
Where there has been local mischief due to inflammation the dead leucocytes must be removed, and this is done either by their being converted into pus in one mass, and making their way through the tissues to the nearest surface, whether of skin or mucous membrane, from which it can be discharged, or they may undergo a process of fatty degeneration and absorption, leaving behind in some cases cheesy matter, in others hard connective tissue.
Red corpuscles (Bordet, Ehrlich and Morgenroth), leucocytes and spermatozoa (Metchnikoff).
Such an effect may be demonstrated outside the body by making a (actiopsonic suitable mixture of (a) a suspension of the particular bacterium, (b) the serum to be tested, and (c) leucocytes of a normal animal or person.
The number of bacteria contained within a number of, say fifty, leucocytes can be counted and the average taken.
The average number of bacteria contained within leucocytes in the case tested, divided by the number given by the normal serum, is called the phagocytic index.
The behaviour of certain cells, especially leucocytes, with regard to anti-bacterial sera, the presence of phagocytosis cannot be regarded as the essence of immunity, but rather the evidence of its existence.
Thus the apparent increased activity of the leucocytes is due to a preliminary effect of the opsonins on the bacteria.
There is some evidence that in certain cases anti-substances may act upon the leucocytes, and to these the name of " stimulins " has been given.
While in immunity there probably occurs no marked change in the leucocytes themselves, it must be admitted that the increased destruction of bacteria by these cells is of the highest importance.
This, as already pointed out, depends upon the increase of opsonins, though it is also to be noted that in many infective conditions there is another factor present, namely a leucocytosis, that is, an increase of the leucocytes in the blood, and the defensive powers of the body are thereby increased.
Evidence has been brought forward within recent years that the leucocytes may constitute an important source of the antagonistic substances which appear in the serum.
Whether bacteria will be destroyed or not after they have been ingested by the leucocytes will depend upon the digestive powers of the latter, and these probably vary in different species of animals.
As regards the former, leucocytes are guided chiefly by chemiotaxis, i.e.
Variations in the bactericidal action of the serum in vivo, variations in the chemiotactic or opsonic properties of the serum in vivo, and variations in the digestive properties of the leucocytes of the particular animal.
The leucocytes or white blood corpuscles are very markedly affected by quinine, the characteristic "amoeboid" movements of the cells being arrested.
Hence quinine stops the process of diapedesis or emigration of the leucocytes from the blood-vessels into the tissues, and if applied to the, extravascular spaces it arrests the leucocytic movements there.
The explanation that this influence on the leucocytes explained the favourable action of quinine on certain inflammatory processes no longer holds, since we know that the inflammatory conditions are of microbic origin, and that the movements of the leucocytes are not objectionable, but highly desirable as a means of defence against bacteria and their products.
This product is largely derived from the nuclei of the leucocytes, which contain large quantities of the nucleo-proteids, of which uric acid is a decomposition product.
Quinine administered by the mouth or by any other means will soon enter the blood, and will then kill the haematozoon malariae, whether it be free in the blood-plasma, in the leucocytes or in the red blood corpuscles.