Gametocyte

“ Male and female gametocytes are distinguished (roughly) by the arrangement of the pigment-grains; in the former, they are fairly evenly scattered throughout the cytoplasm, but in the megagametocytes the pigment tends to be aggregated centrally, around the nucleus. As they become full-grown and mature, however, the gametocytes lose their crescentic form and assume that of an oval, and finally of a sphere. At the same time, they are set free from the remains of the blood corpuscle. ”

“ The parent-individuals of the microgametes, or microgametocytes, are distinguished as a general rule by clearer protoplasm, free from coarse granulations, and a larger nucleus, more rich in chromatin. The macrogametocytes, on the other hand, usually have coarsely granular cytoplasm, rich in reserve food-stuffs, and a relatively small nucleus. The gametocytes produce the gametes by methods that vary according to the degree of specialization of the gametes. ”

“ The cytoplasm of the male gametocytes is pale-staining and the nucleus is elongate, while the cytoplasm of the females is darker and the nucleus is smaller and round. Formation of male gametes from male gametocytes (the so-called process of “exflagellation”) may occur on a slide of drawn infected blood, also fertilization, and formation of the oökinete, as first seen by MacCallum. ”

“ The male elements (microgametes) are formed in a manner essentially comparable to that in which the formation of merozoites takes place. Although the details of the nuclear changes and divisions vary somewhat, the end-result is similar, a number of little nuclear agglomerations being evenly distributed at the surface (VII. ♂) Each of these elongates considerably, becoming comma-shaped and projecting from the gametocyte. Nearly all the body of the male gamete (VIII. ♂) consists of chromatin, the cytoplasm only forming a very delicate zone or envelope around the nucleus. ”

“ The male cell resembles the female cell very closely, except that the protoplasm is hyaline and homogeneous-looking, whilst that of the female cell is granular. It has already been noted that when the blood is withdrawn from the body certain of the malarial parasites become flagellated. These flagefla may be looked upon as sperm elements, which, forming in the male gametocyte, are extruded from that cell, and, once set free, seek out the granular female gametocytes. A single flagellum becomes attached to a small projection that appears on the female cell ”

“ A-G, Amoebula of quartan parasite to sporulation; H, its gametocyte; I-M, amoebula of tertian parasite to sporulation; N, its gametocyte; O, T, "crescents" or gametocytes of Laverania; P-S, sperm-formation ”

“ Parthenogenesis is not recognized as occurring in the protozoa, but was supposed by Schaudinn to take place in the case of the malaria parasite and to be responsible for the relapses of that infection.
These sporonts, still in the blood of the vertebrate host, develop into sexually differentiated cells (gametocytes) , which are quiescent until they are removed from the blood; when this occurs both male and female cells extrude two polar bodies preparatory to the sexual process, and are then known as gametes. ”

“ A considerable proportion of these free, dropsical-looking bodies, with active hæmozoin, are probably male gametocytes which, after being placed on the micro- scope slide, and after escaping from corpuscles, have failed to project their microgamete filaments; others, doubtless, are granular female gametes. The failure to project microgametes, in many instances, is probably not normal, but an effect of mechanical dis- turbance from pressure of the cover-glass, or of other circumstances inherent to the artificial conditions under which we necessarily observe these bodies. ”

“ Male gametes. 1. Young form similar to female one. 2. Half grown form showing central chromatin. 3. Full grown microgametocyte showing large amount of centrally placed chromatin with light blue protoplasm surrounding. 4. Division of chromatin occurring in microgametocyte and developing in wet preparation. Note.—Chromatin division in gametes does not take place until blood is withdrawn. 5. Spermatozoon like microgametes developing from the microgametocyte. This only occurs in wet preparations or in the stomach of the mosquito.
Quartan Parasites ”

“ It is often found that not only are the gametes differentiated, but that their immediate progenitors may also exhibit characters which mark them off from the ordinary or indifferent individuals of the species. In such cases the parent-forms of the gametes are termed gametocytes, and they may differ amongst themselves in characters which render it possible to distinguish those destined to produce microgametes from those which will produce the other sex. ”

“ We know that living tissues give off products, and that these are not merely pure CO2 and H2O, but complicated compounds. The theory proposed by me in 1908 was that we have within the gonads numerous gametocytes whose chromosomes contain factors corresponding to the different parts of the soma, and that factors or determinants might be stimulated by products circulating in the blood and derived from the parts of the soma corresponding to them. ”

“ Once the parasite begins to divide, the trophozoites are called schizonts, consisting of many daughter merozoites (blood schizogony) . Eventually, the infected erythrocytes are lysed by the merozoites, which subsequently invade other erythrocytes, starting a new cycle of schizogony. The duration of each cycle in P. falciparum is about 48 hours. In non-immune humans, the infection is amplified about 20-fold each cycle. After several cycles, some of the merozoites develop into gametocytes, the sexual stage of malaria, which cause no symptoms, but are infective for mosquitoes [5] . ”

“ Wright's stain the nucleus is less deeply colored than that of the lymphocyte, while the cytoplasm is very pale blue or colorless, and sometimes contains a few reddish granules. The size of the cell, the width of the zone of cytoplasm, and the depth of color of the nucleus are the points to be considered in distinguishing between large mononuclears and lymphocytes. When large forms of the lymphocyte are present, the distinction is often difficult or impossible. It is then advisable to count the two cells together as lymphocytes. ”

“ We know little if anything of the relation between the two conjugating cells or gametes, of the real nature of the attraction that causes them to approach each other and ultimately unite together. We have, it is true, some evidence that one cell affects the other by some chemical action, as for instance in the fact that the mobile male gametes of a fern are attracted to a tube containing malic acid, but this may be merely an influence on the direction of movement of the male gamete, while there are cases in which neither cell is actively mobile. ”

“ Sharply to be distinguished from the lymphocytes is the second group: the "large mononuclear leucocytes." These are large cells about twice to three times the size of the erythrocytes. They possess a large oval nucleus, as a rule eccentrically situated and staining feebly, and a relatively abundant protoplasm. The latter is free from granulations, feebly basophil, and in contrast to the protoplasm of the lymphocytes stains less deeply than the nucleus. This group is present in normal blood in but small numbers (about 1%) . ”

“ The shape of the gametes is not amoeboid, as is that of the twenty-four to thirty-six-hour-old schizont, but round or oval. The full-grown gametes have the pigment distributed and the chromatin in a single aggregation—just the opposite of nonsexual parasites. The male gamete stains a light grayish blue and has a very large amount of chromatin, usually centrally placed. The female gamete stains a pure blue, has only about one-tenth as much chromatin as plasma, with the chromatin often placed at one side. The pigment of the female gamete is dark brown while that of the male is yellowish brown. ”

“ Very constant also is a marked absolute, and often a relative, increase of eosinophiles and basophiles. Polymorphonuclear neutrophiles and lymphocytes are relatively decreased.
[p. 210] The red cells show the changes characteristic of a severe secondary anemia, except that nucleated reds are commonly abundant; in fact, no other disease gives so many. They are chiefly of the normoblastic type. Megaloblasts are uncommon. Blood-plaques are generally increased.
2. Lymphatic Leukemia.—This form may be either acute or chronic. There is marked loss of hemoglobin and red corpuscles. ”

“ In human blood the following varieties of leucocytes may be distinguished:—
1. The Polymorphonuclear Cell.—This possesses a nucleus of very complicated outline and a fair amount of protoplasm filled with numbers of fine granules which stain with eosin. They vary in size but are usually about 0.01 mm. in diameter. They are highly amoeboid and phagocytic, and form about 70% of the total number of leucocytes.
2. The Coarsely Granular Eosinophile Cell.—These large cells contain a number of well-defined granules which stain deeply with acid dyes. The nucleus is crescentic. ”

“ They [Pg 79] are about as large as the small lymphocytes, possess a rounded deeply stained nucleus, and a small shell of protoplasm studded with a neutrophil granulation. The relatively deep stain of the nucleus and the small share of the protoplasm in the total cell body prevent confusion with the small forms of myelocytes, which never reach such small dimensions. The neutrophil pseudolymphocytes are exceedingly infrequent, and represent products of division of the polynuclear cells; they were first described by Ehrlich in a case of hemorrhagic small-pox. ”

“ This simple method holds good for all counts of 1,000,000 or more. Thus, a count of 2,500,000 is 50 per cent. of the normal. If, then, the hemoglobin has been estimated at 40 per cent., divide 40 (the percentage of hemoglobin) by 50 (the percentage of corpuscles) . This gives 4/5, or 0.8, as the color index.
IV. ENUMERATION OF LEUKOCYTES
The normal number of leukocytes varies from 5000 to 10,000 per cubic millimeter of blood. The number is larger in robust individuals than in poorly nourished ones, and if disease be excluded, may be taken as an index of the individual's nutrition. ”

“ 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. ”

“ Myelocytes are rare.
The red corpuscles show the changes usual in severe secondary anemia. Erythroblasts are seldom abundant. Blood-plaques are decreased.
3. Pseudoleukemia (Hodgkin's disease) resembles lymphatic leukemia in that there is marked and progressive enlargement of the lymph-nodes. There is, however, no distinctive blood-picture. The changes in hemoglobin and red cells resemble those of a moderate symptomatic anemia, with rather low color-index. The leukocytes are commonly normal in number and relative proportions. ”

“ 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. ”

“ An index to this condition is the differentiation of the gametangia with respect to the number of gametes developed. The female gametangium tends to reduce the number until a single egg takes all the material of the oogonium. The male gametangium increases the number of sexual products, becoming an antheridium that may develop numerous sperms.
Third Stage.—Isogamy in that peculiar form when the gametes are similar in form at the time of their discharge from the gametangia, but different at the time of fusion, because the female gamete becomes a motionless cell. ”

“ The mononuclear cells of man however are finally transformed into the neutrophil granulated cells, whilst the cells of Kurloff remain free from granules in the course of their metamorphosis. In acute leucocytosis in the guinea-pig only the pseudo-eosinophil polynuclear cells are increased, which wander as such out of the bone-marrow, but not the polynucleated non-granulated forms, which but slowly grow to maturity in the blood. Thus the peculiarities of guinea-pig's blood, in which two kinds of polynuclear cells are recognisable, throw light upon the corresponding conditions in human blood. ”

“ Their voracity is useful for the preservation of the social organism. By eliminating old, exhausted, diseased cells they rejuvenate the structure and prepare the way for new generations. And when the fecundity of these is exhausted the leucocytes come in to occupy the vacated situations, and conduct the organism thus patched up through a senile degeneracy to natural death.
The leucocytes, white globules, or phagocytes, by virtue of their mobility, are found everywhere—in the blood, in all the organs, and in all parts of the body—but are perhaps most abundant in the blood. ”