animals, and the sensations of a plasmodium obey like ours the law of Weber.

Chemiotaxis is a sort of chemical sense.

The phagocytes have also a sort of tactile sensibility. The leucocytes in their reaction apply themselves to the exciting body over the largest surface possible.

In defensive phagocytosis, the struggle of the body against the parasitic invaders, it is not necessary to suppose any purposeful cause but simply a function developed by evolution and selection. "Those lower animals in which the motile cells directed themselves towards the enemy, engulfing and destroying them, survived, whereas others in which the phagocytes did not act, were condemned to perish. All the useful characters and among them those which are concerned in the inflammatory reaction have become fixed and transmitted without the intervention of any preconceived purpose whatever" (Metchnikoff). Thus in the invertebrates with soft skins in which bacterial invasion occurs easily there has been a selective process at work in the phagocytic apparatus and the defensive measures have become perfected. Among the invertebrates possessing a natural protection, such as a chitinous covering, infection is rarer, but the means of defence have not found suitable conditions for their employment and development, so that the infected organism succumbs. The phagocytic arrangements are much reduced in the Insects, and in these the parasitic fungi have great difficulty in penetrating the cuticle, but if they are successful the insect is destroyed (for example in the beetle Cleonus punctiventris invaded by Isaria destructor). The nematode worms which are protected by a thick skin do not even possess cells capable of movement.

The phagocytes of man are both fixed and motile. Among the fixed are the large mononuclears, the Kuppfer cells of the liver, certain endothelial cells of the lung (the dust-cells) and the myeloplaxes of the bone-marrow. The motile phagocytes are the white corpuscles or leucocytes in general (except the small lymphocytes), the polymorphs, the eosinophils, the large mononuclear cells of the blood and of the lymphatic organs.

Metchnikoff has divided the phagocytes into macrophages and microphages; the former are chiefly concerned in the absorption of cells and cellular debris, and include the large mononuclears, the fixed phagocytes of the spleen, of the peritoneum and of the lymphatic glands. They digest the blood corpuscles and other phagocytes. The microphages

FIG. 52. Different leucocytes.
Polymorph.-
.-2. Microphage (poly-
morph) taking up staphylococci, st.
-3. Small lymphocyte.-4. Eo-
sinophil.-5. Large mononuclear
(macrophage). 6. Macrophage
from the peritoneum of a guinea-
pig taking up red corpuscles. — 7.
Macrophage from the peritoneum
taking up polymorphs (micro-
phages) and blood corpuscles.

are the polymorphs; their principal function is to digest bacteria. There are exceptions. In certain cases the microphages take up cells (red cells among others), while in certain. cases the macrophages take up bacteria; the large mononuclears surround the tubercle bacillus producing the giant cell, and take up also the spirochetes of fever and of

recurrent

syphilis.

It has sometimes been maintained that the phagocytes only take up dead bacteria and not living virulent ones; this is a mistake to which it will be necessary to refer again in connection with immunity. Under the microscope there can be seen inside the phagocytes living and even motile bacilli, and cultures can be obtained by inoculating into broth phagocytes full of microbes the leucocytes are destroyed and the liberated bacteria multiply. They were still quite alive therefore, although already seized by the phagocytes.

The phagocytes secrete digestive ferments. Rossbach has demonstrated the existence of a starch-splitting ferment in the leucocytes of the tonsils. The cells of pus can digest fibrin and gelatine, and must thus secrete proteolytic ferments. In cases of acute muscular atrophy the progressive digestion of

the muscle fibres can be observed in the interior of the phagocytes. The bacilli or cells taken up by the phagocytes become distorted, and before disappearing lose their affinity for stains. In the various cases of immunity the phagocytes digest the bacteria by means of endo-enzymes.

The surface of the skin, and in particular of the mucous membrane, is being continually besieged by bacteria, and never a moment passes but some point in the body is in a state of subinflammation. The phagocytes are in continual operation on the surface of the tonsils, of the mucous membrane of the intestine, and of the alveoli of the lungs.

Phagocytosis plays a pre-eminent part in chronic infections, especially in tubercle, and the tubercle itself is a phagocytic formation. In contrast to Baumgarten's contention that the tubercle is built up by epithelial cells, fixed cells from the diseased tissue itself, lung, liver, or kidney, Metchnikoff and his pupils have proved that it is really composed of migratory mesodermic cells which have come from elsewhere to the infected point. Borrel followed the formation of the tubercle from the time of the first contact between the white corpuscles and the bacilli, and found that injected bacilli were engulfed by the polymorphs while still in the circulation. The polymorphs perish and degenerate (in two or three days) and are followed by the macrophages which fuse together into a sort of little plasmodium with several nuclei, which is characteristic of the tuberculous lesion, and is called by the anatomists the giant cell. Later, the tubercle may soften, and there may be a new afflux of polymorphs attracted chiefly by the bacteria of a secondary infection.

In the squirrel-rat spermophilus, a rodent rather resistant to tubercle, the phagocyted bacilli lose their staining properties, degenerate, swell up and finally appear as yellowish bodies, such as are never observed either in cultures or outside the cells, and can only be residues of phagocytic digestion. In another rodent, the jerboa, there is found, especially in tubercle of the spleen, instead of bacilli amorphous bodies built up of concentric layers, which are encrusted with

phosphate of lime and may be dissolved by an acid. Observation of these tubercles at different stages shows that the concentric layers correspond to secretions of the bacillus which has been defending itself against the phagocytes. Analogous formations are known in actinomycosis (the club-forms of the granules). There is no essential difference between the struggle of the tubercle bacillus against the giant cell and the Tubercle bacillus

FIG. 53-Giant cell from the spleen of the jerboa: it contains a tubercle bacillus surrounded by concentric layers. (Metchnikoff.)

struggle of the gregarines and the nematodes (larvæ of Gordius or Rhabditis) against the phagocytes of the worm.

Inflammation is thus defined by phagocytosis: the vessels and nerves have their importance, but are merely accessory. Infection, inflammation, and immunity can all be seen in miniature in the examples of the Bipinnaria with its splinter surrounded by motile cells, and of the Daphnia with its globules in the act of devouring the spores of Monospora.

CHAPTER VII

THE PATHOGENIC PROTOZOA: FILTER-PASSING VIRUSES

Protozoal diseases-Laveran's discovery-Importance of the morphology and the life-cycle-Intracellular protozoa-Heredity in bacterial and in protozoal diseases-Diseases due to the so-called invisible microbes. -The ultramicroscope-Filtration-Various types of virus capable of passing filters-Microbes of extreme minuteness described in the pustular diseases of the epithelium--Lesions of the infected cells.

THE PATHOGENIC PROTOZOA

THE name of Pasteur must be inscribed at the head of this chapter. It was by his study of pébrine, a protozoal disease of silk-worms, that our ideas on the microbial diseases were so much advanced.

The studies on anthrax, the labours of Koch and the great discovery of the attenuation of viruses led the new science in the direction rather of bacteriology; the protozoa had even been somewhat forgotten, when in 1880 Laveran discovered among them the cause of malaria. Since that date their importance in pathology has never ceased to grow.

The methods of research cannot be quite the same as in bacteriology; they have not the same simplicity as the bacteria. In the case of the tubercle bacillus, the cholera vibrio, and the streptococcus, we practically know only one single constant fixed form for each, and there is no sign of a life-cycle. The majority of the pathogenic protozoa on the contrary go through a cycle in their existence whose successive forms may be very diverse and this cycle may take place, not in a single host, but often in two different ones. The discoveries of Ross on the