RESPONSE OF TISSUES TO  STIMULATION A stimulus may be defined as every

change of the external agencies acting upon an organism; and if a stimulus come in contact with a body possessing the property of irritability, i.e. the capability of reacting to stimuli, the result is stimulation (Verworn) . Stimuli comprise chemical, mechanical, thermal, photic and electrical changes in the environment of the organism . A stimulus may act on all sides and induce a general effect with-out direction of movement, but in the production of movement in a definite direction the stimulus must be applied unilaterally . Stimuli applied generally, not unilaterally, in most cases induce increased divisibility of the cells of the part . Thus the poison of various insects induces in plants the cellular new formation known as a gall-nut; a foreign body implanted in a limb may become encysted in a capsule of fibrous tissue; septic matter introduced into the abdomen will cause proliferation of the lining endo(epi)thelium; and placing an animal (salamander, Galeotti) in an ambient medium at a higher temperature than that to which it is accustomed naturally, increases the rapidity of cell-division of its epithelium with augmentation of the number of karyokinetic figures . Hair and some other like structures grow luxuriantly on a part to which there is an excessive flux of blood . Bone (e.g. drill-bones) may develop in a soft tissue with no natural bone-forming tendencies, as a result of interrupted pressure, or a fatty tumour may arise in the midst of the natural subcutaneous fat in the same circumstances . Among stimuli acting unilaterally, perhaps none has proved more interesting, in late times, than what is known as Chemiotaxis . By it is meant the property an organism endowed with the power of movement has to move towards or away from a chemical stimulus applied unilaterally, or, at any rate, where it is applied in a more concentrated state on the one side than on the others, and more particularly where the concentration increases gradually in one direction away from the living organism acted upon . Observed originally by Engelmann in bacteria, by Stahl in myxomycetes, and by Pfeffer in ferns, mosses, &c., it has now become recognized as a widespread phenomenon . The influence of the chemical substance is either that of attraction or repulsion, the one being known as ,posita`es the other as negative chemiotaxis . The female organs of certain cryptogams, for instance, exert a positive chemiotactic action upon the spermatozoids, and probably, as Pfeffer suggests, the chemical agent which exerts the influence is malic acid .

No other substance, at least, with which he experimented had a like effect, and it is possible that in the archegonium which contains the ovum malic acid is

present . 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 . 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-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 . Some bacteria, such as those of anthrax, are seized upon in the same manner, indeed; very much as small algae and other particles are incorporated and devoured by amoeba . Melanine particles formed in the spleen in malaria, which pass along with the blood through the liver, are appropriated by the endothelial cells of the hepatic capillaries, and are found embedded within their substance . If the particle enveloped by the protoplasm be of an organic nature, such as a bacterium, it undergoes digestion, and ultimately becomes destroyed, and accordingly the term " phagocyte " is now in common use to indicate cells having the above properties . This phagocytal action of certain cells of the body is held by Metchnikoff and his followers tohave 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 .

Among the Iatest is that of Metchnikoff: " Inflammation generally," he says, " must be regarded as a phagocytic reaction on the part of the organism against irritants . This reaction. is carried out by the mobile phagocytes sometimes alone, sometimes with the aid of the vascular phagocytes, or of the

nervous system." Given a noxious agent in a tissue, such, let us say, as a localized deposit of certain bacteria, the phagocytes swarm towards the locality where the bacteria have taken up their residence . They surround individual bacteria, absorb them into their substance, and ultimately destroy them by digestion . The phagocytes are attracted from the blood vessels and elsewhere towards the noxious focus by the chemiotaxis exerted upon them by the toxins secreted by the bacteria contained within it . The chemiotaxis in this instance is positive, but the toxins from certain other bacteria may act negatively; and such bacteria are fraught with particular danger from the fact that they can spread through the body unopposed by the phagocytes, which may be looked upon as their natural enemies .