scholarly journals STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III

1936 ◽  
Vol 64 (2) ◽  
pp. 307-330 ◽  
Author(s):  
John F. Enders ◽  
Morris F. Shaffer ◽  
Chao-Jen Wu
Keyword(s):  
Virulent Strain ◽  
Blood Stream ◽  
The State ◽  
The Body ◽  
Polymorphonuclear Leucocytes ◽  
Natural Immunity ◽  
Phagocytic Cells ◽  
Fixed Tissue ◽  
Type Iii ◽  
Pneumococcus Type

Among the experimental findings reported in this paper to which we wish to give particular emphasis are the following: 1. The results which follow the intravenous injection into rabbits of two strains of Pneumococcus Type III of different degrees of virulence vary with the state of the capsule. Thus when this structure is completely developed both remain in the blood. A culture of either strain begins to become susceptible to the blood-clearing mechanism contemporaneously with the onset of capsular degeneration and the initiation of other concomitant changes at the surface of the organism (cf Paper II), which occur much earlier with the less virulent strain. 2. When, in either case, removal from the blood stream occurs, this is effected by the phagocytic cells of the body. There is no suggestion that a new or unknown mechanism is involved. The greatest share of the burden is borne by the fixed phagocytic cells of the liver and spleen, and to a less extent by those of the lung and bone marrow. Nevertheless, it has been demonstrated that the polymorphonuclear leucocytes may also participate. 3. Phagocytosis by the leucocytes of the normal animal either in intro or in vivo has been observed only at such a time as the capsule has become impaired. Ingestion of the organisms by the fixed tissue cells appears also to be effective only under the same condition and is accordingly observed with much younger cultures of the less virulent strain. 4. Following their removal from the blood and their accumulation within the fixed phagocytes of the organs, destruction of most of the cocci proceeds within 2 to 4 hours. Both strains are destroyed provided they are in the state favorable to phagocytic attack. 5. Evidence has been presented which indicates that just as in vitro, so in a local area of inflammation within the body, aging with attendant capsular loss and increasing susceptibility to phagocytosis may take place. 6. With organisms from either strain a variable period of lag follows their injection into the blood stream, even when they are introduced in a state of active multiplication and complete encapsulation. 7. Differences in virulence for rabbits of two strains of Pneumococcus Type III do not imply that this animal possesses a defensive mechanism which is absent in other species, since it has been possible to demonstrate similar differences when the organisms are injected intravenously into mice. This fact indicates that the factors determining the degree of virulence of these strains are to be sought in the organisms themselves, rather than in the kind of host.

scholarly journals STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III

1936 ◽  
Vol 64 (3) ◽  
pp. 425-438 ◽  
Author(s):  
John F. Enders ◽  
Chao-Jen Wu ◽  
Morris F. Shaffer
Keyword(s):  
Elevated Temperatures ◽  
Blood Stream ◽  
The Body ◽  
Intravenous Route ◽  
Natural Immunity ◽  
Phagocytic Cells ◽  
Adjuvant Effect ◽  
Type Iii ◽  
Essential Components ◽  
Pneumococcus Type

Since there is no evidence for the occurrence of type specific antibody in the normal rabbit and since, as we have shown, the Pneumococcus Type III whether avirulent or virulent is not removed from the blood stream or destroyed when the capsule is intact, the following factors which have been revealed in the course of our work appear to represent certain essential components, if not the complete mechanism, upon which the natural immunity of the rabbit against this organism depends. (a) The elevation of the body temperature after intravenous infection to 41°C. or thereabouts and its maintenance for varying periods. (b) The ability of the phagocytic cells, both fixed and mobile, to attack any cocci which have become vulnerable through the deterioration of capsular integrity. (c) The adjuvant effect of an antibody, reacting with the somatic C carbohydrate, which enhances the phagocytosis of such organisms as no longer possess a completely intact envelope. Conversely, the varying degrees of virulence for rabbits observed among Pneumococcus Type III strains are based upon: (a) differences in the ability of the organisms to multiply at the elevated temperatures encountered in the infected host. Strains markedly susceptible to the harmful influence of this factor fail to induce a generalized fatal infection. Not all "thermo-resistant" strains are highly virulent, however, and these may contrast sharply with regard to (b) size of the capsule and the ease with which it is impaired or completely lost. The capsules must be maintained intact for a sufficient time until multiplication of the organisms can proceed to such a degree that death of the host results. Avirulent strains even when capable of growth at 41°C. appear to be unable to satisfy this requirement. The differences in virulence of various strains apparently conditioned by these factors are not limited solely to the case of the rabbit, since for at least two strains similar differences in virulence have been shown to exist when the intravenous route of infection is employed in mice.

scholarly journals STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III

1936 ◽  
Vol 64 (2) ◽  
pp. 281-305 ◽  
Author(s):  
Morris F. Shaffer ◽  
John F. Enders ◽  
Chao-Jen Wu
Keyword(s):  
Bacterial Species ◽  
Early Period ◽  
Avirulent Strain ◽  
Polymorphonuclear Leucocytes ◽  
Natural Immunity ◽  
Experimental Conditions ◽  
Animal Body ◽  
Type Iii ◽  
Antigenic Properties ◽  
Pneumococcus Type

The results which have been presented show that under the conditions of artificial cultivation at 37°C. definite differences exist between two smooth strains of Pneumococcus Type III both of which are highly virulent for mice by the intraperitoneal route, but which may be sharply distinguished in their virulence for rabbits. These differences consist in the size of the fully developed intact capsule and the interval of time required for its loss. The somewhat smaller capsule of the avirulent strain, well formed and easily demonstrable during the early period of growth, diminishes quickly, while the large capsule of the strain virulent for rabbits is retained for a considerably longer period. Closely correlated with the time at which this reduction of capsule occurs is the appearance of changes in the surface properties of the bacteria which are revealed by a shifting of the range of acid agglutination, susceptibility to clumping in anti-R serum and ingestion by normal adult human polymorphonuclear leucocytes and serum. Since it has been shown that these alterations as growth continues, result in a loss of characteristics which distinguish the strictly type specific, fully capsulated pneumococcus and ultimately lead to a state temporarily approximating that of the completely avirulent R form, and since under the experimental conditions they are inaugurated sooner, advance more rapidly and are more complete in the rabbit avirulent organism, we believe that they may partly account for difference in rabbit virulence of the two strains. In the following paper an attempt has therefore been made to correlate this behavior in vitro with the events attendant upon inoculation into the animal body. The studies of Clark and Ruehl (16), Henrici (17), Bayne-Jones and Adolph (18) and others have demonstrated a marked increase in the size of the bacterial cell associated with the early phases of growth. These authors have dealt chiefly with noncapsulated rod forms and even Clark and Ruehl who included cultures of various cocci do not make reference to variations in capsule size. Recently Seastone (19) has called attention to the large volume occupied by young capsulated streptococci. Similarly we have found that increase and decrease of Pneumococcus Type III volume appears to be due largely to the formation of capsule in young cultures and its subsequent loss as the organisms age. Because of the relatively great proportion of capsule in comparison with soma, a greater disparity exists between the volume of young and old pneumococci than that found by those who have studied bacteria lacking this structure. Of interest in connection with our observations are those of Preisz (20) on the nature of the capsules of virulent anthrax bacilli and strains attenuated by cultivation at 42.5°C. The latter produced soft, rapidly dissolving capsules while such structures in the former were characteristically firm and were retained by the bacilli for longer periods. This worker also noted in confirmation of the earlier work of others, that the capsules of B. anthracis are lost during the course of growth in serum media and in the subcutaneous tissues of the susceptible mouse. We have demonstrated that the R variants derived under the same conditions from the two smooth strains of Pneumococcus Type III reveal certain characteristics by which they may be distinguished from each other in respect to cell and colony morphology, growth in broth, as well as growth at 41°C. (cf. Paper I). By employing the method of Griffith, these two R variants have been induced to revert to the S form. Following the injection into mice of the various possible combinations of living R variant and the killed S organisms of either rabbit virulent or avirulent strain, as well as very large numbers of the R variant alone, S forms emerged which in their various attributes, notably that of virulence for rabbits, resembled the original smooth strain from which the particular R variant involved was dissociated. The function of the smooth killed organisms in the process of transformation appeared to be only that of a stimulus toward reversion to the S. They apparently play no rôle in determining the virulence or the growth properties of the resulting S form. These observations indicate that the factors involved in virulence are conditioned by stable physiological properties peculiar to the individual strain and that although temporarily inactive during the R state, they are again resumed unaltered upon the transition to the S form. They serve also to reemphasize the fact, apparent from several studies but perhaps not sufficiently realized, that the R variants of the pneumococcus, even though obtained under the same conditions from the same type but from different strains, may vary definitely in their various attributes. Finally, they strongly suggest that the degree of virulence of a given strain of a bacterial species may be determined not only by its ability to multiply in the environment of the host and to synthesize certain substances of definite chemical and antigenic properties, but also by the capacity to elaborate these in greater or lesser degree and under the conditions of parasitism within the animal body to maintain them in contact with the soma of the cell in such state that they afford an efficient barrier to the defensive mechanisms of the host.

scholarly journals STUDIES ON VITAL STAINING

1930 ◽  
Vol 51 (3) ◽  
pp. 379-394 ◽  
Author(s):  
H. P. Smith
Keyword(s):  
Vital Staining ◽  
Blood Stream ◽  
Partition Ratio ◽  
The Body ◽  
Phagocytic Cells ◽  
Bile Fistula ◽  
Prolonged Retention ◽  
Large Dosage ◽  
Partial Correction ◽  
Reticulo Endothelial System

Brilliant vital red injected into the blood stream of dogs is slowly taken up by phagocytes in various parts of the body, but eventually an equilibrium is established, after which the concentration as measured in the plasma remains almost constant for long intervals of time. This equilibrium can be disturbed by injecting more dye, and in this case the phagocytes resume ingestive activity, apparently with normal or nearly normal vigor. This activity continued until a rather large part of the newly injected dye has been removed, and as the reaction again slows up we note that both plasma and tissues contain more dye than before. It is difficult to be certain that the distribution ratio of dye between plasma and tissues remains unaltered with dosage, but evidence indicates that for non toxic doses, at least, this is approximately true. This study of this partition ratio is complicated by the fact that the liver slowly excretes dye into the bile, and this helps to reduce the amount of dye in the body. Partial correction for this factor can be made by ascertaining the dye output in bile fistula dogs. These latter studies show that dye elimination into bile is relatively less efficient when large doses of dye are given to the animal than with smaller dosage. This undue retention of dye in the body with large dosage helps to maintain the dye concentration in the plasma at unduly high levels. These peculiarities in liver excretion have an important bearing on liver physiology in general, and in addition they also have an important application in connection with the theory of "blockade of the reticulo-endothelial system." It is now obvious that prolonged retention of dye in the blood stream does not of itself prove that this group of phagocytic cells is "blocked" against the entrance of foreign material. Altered excretion by liver, kidney, etc. must be ruled out before we can accept such data as evidence of "blockade."

scholarly journals A HISTOLOGICAL STUDY OF TYPHOID FEVER

1898 ◽  
Vol 3 (6) ◽  
pp. 611-638 ◽  
Author(s):  
F. B. Mallory
Keyword(s):  
Blood Vessels ◽  
Lymphoid Tissue ◽  
General Circulation ◽  
Intestinal Tract ◽  
Histological Study ◽  
The Body ◽  
Polymorphonuclear Leucocytes ◽  
Phagocytic Cells ◽  
Mesenteric Lymph Nodes ◽  
Intestinal Lymphoid Tissue

The typhoid bacillus produces a mild diffusible toxine, partly within the intestinal tract, partly within the blood and organs of the body. This toxine produces proliferation of endothelial cells which acquire for a certain length of time malignant properties. The new-formed cells are epithelioid in character, have irregular, lightly staining, eccentrically situated nuclei, abundant, sharply defined, acidophilic protoplasm, and are characterized by marked phagocytic properties. These phagocytic cells are produced most abundantly along the line of absorption from the intestinal tract, both in the lymphatic apparatus and in the blood-vessels. They are also produced by distribution of the toxine through the general circulation, in greatest numbers where the circulation is slowest. Finally, they are produced all over the body in the lymphatic spaces and vessels by absorption of the toxine eliminated from the blood-vessels. The swelling of the intestinal lymphoid tissue of the mesenteric lymph nodes, and of the spleen is due almost entirely to the formation of phagocytic cells. The necrosis of the intestinal lymphoid tissue is accidental in nature and is caused through occlusion of the veins and capillaries by fibrinous thrombi, which owe their origin to degeneration of phagocytic cells beneath the lining endothelium of the vessels. Two varieties of focal lesions occur in the liver: one consists of the formation of phagocytic cells in the lymph spaces and vessels around the portal vessels under the action of the toxine absorbed by the lymphatics; the other is due to obstruction of liver capillaries by phagocytic cells derived in small part from the lining endothelium of the liver capillaries, but chiefly by embolism through the portal circulation of cells originating from the endothelium of the blood-vessels of the intestine and spleen. The liver cells lying between the occluded capillaries undergo necrosis and disappear. Later the foci of cells degenerate and fibrin forms between them. Invasion with polymorphonuclear leucocytes is rare. Many of the phagocytic cells pass through the liver and lungs, and get into the general circulation. A few come from the abdominal lymphatics through the thoracic duct.

scholarly journals THE DISTRIBUTION AND STORAGE OF BLUE ANTIGENIC AZOPROTEINS IN THE TISSUES OF MICE

1949 ◽  
Vol 90 (5) ◽  
pp. 425-446 ◽  
Author(s):  
Heinz Kruse ◽  
Philip D. McMaster
Keyword(s):  
Kupffer Cells ◽  
Serum Proteins ◽  
Blood Stream ◽  
Body Fluids ◽  
The Body ◽  
Blue Dye ◽  
Protein Ratio ◽  
Fixed Tissue ◽  
Mesenteric Node ◽  
Antigenic Material

Intensely blue dye-azoproteins have been prepared by diazotization and coupling of the highly indiffusible blue dye T-1824, Evans blue, with various serum proteins and egg albumin. The products, whether purified by precipitation with alcohol or by chromatography, have a constant dye-to-protein ratio and tests have shown them to be essentially free from unlinked dye. An extremely diffusible dye, echt-säure-blau, has also been coupled to bovine γ-globulin. These materials are adapted to physiological experimentation. They seem to behave in the bodies of mice like other proteins; they fail to appear in either the bile or urine of normal animals, and they are strongly antigenic. When these soluble antigenic azoproteins are injected into the blood stream of mice for the first time they enter reticulo-endothelial cells in almost every organ of the body; the final distribution is like that of intravenously injected, finely divided particulate matter. The azoproteins appear in the cells which classical immunological studies have shown to be active in removing particulate antigenic materials or bacteria from the blood or body fluids. The Kupffer cells of the liver and sinus and reticular cells in lymph nodes, especially the great mesenteric node, are particularly active in the removal of the blue antigens from the blood, but many other R-E cells are active to a lesser degree. The storage of the antigenic material is in the cytoplasm only; it has not been seen within nuclei, nor has it been seen within cells of the brain. Serological methods disclose that the blue material seen within Kupffer cells of the liver after as long a period as 2 days is still antigenic in its reactions. The blue azoproteins, therefore, serve excellently as tracer antigens, especially since they can be seen directly in fresh and fixed tissue preparations and in the body fluids.

scholarly journals THE FATE OF TYPHOID BACILLI WHEN INJECTED INTRAVENOUSLY INTO NORMAL RABBITS

1915 ◽  
Vol 22 (4) ◽  
pp. 475-483 ◽  
Author(s):  
Carroll G. Bull
Keyword(s):  
Typhoid Fever ◽  
Blood Serum ◽  
Whole Blood ◽  
Blood Stream ◽  
The Body ◽  
Polymorphonuclear Leucocytes ◽  
Fresh Blood ◽  
Shed Blood ◽  
Destructive Processes

Typhoid bacilli are agglutinated promptly in the circulating blood of normal rabbits and quickly removed from the blood stream. The clumped bacilli accumulate in the organs and are taken up by assembled polymorphonuclear leucocytes in the liver, spleen, and possibly other organs. The phagocyted clumps of bacilli are digested and destroyed by the phagocytes. Hence, destruction of typhoid bacilli intra vitam is brought about by an entirely different process than is the destruction by serum and whole blood in vitro. While the latter is caused by bacteriolysis, the former results from agglutination and intraphagocytic digestion. Lysis by fresh blood serum is not appreciably affected by spleen or kidney pulp, but it is inhibited by liver pulp. The action of the liver is referable to its biliary constituents, which exert anticomplementary action. Probably in certain examples of typhoid fever in man the typhoid bacilli in the circulating blood being inagglutinable cannot be removed by the organs and hence are not phagocyted and destroyed. The observed disparity between the ready destruction of typhoid bacilli by serum and shed blood and the resistance sometimes offered by the bacilli in the infected body is explained by the essential differences in the destructive processes in operation within and without the body.

Perspective – Escape from destruction: how cancer-derived EVs are protected from phagocytosis

2020 ◽  
Vol 2 (1) ◽  
pp. 60-64
Author(s):  
Peter Altevogt ◽  
Marei Sammar ◽  
Laura Hüser ◽  
Viktor Umansky ◽  
Jochen Utikal
Keyword(s):  
Extracellular Vesicles ◽  
Immune Suppression ◽  
Blood Circulation ◽  
Blood Stream ◽  
Phosphatidyl Serine ◽  
The Body ◽  
Hostile Environment ◽  
Phagocytic Cells ◽  
The Stability

There is evidence that cancer-derived extracellular vesicles (EVs) have nearby and distant effects in the body. In order to reach distant sites, EVs need to travel through the blood stream and organs where they encounter a hostile environment in the form or phagocytic cells. However, the stability and homeostasis in the blood circulation and in the tumor microenvironment are not well understood. Phagocytosis is an important mechanism for the clearance of apoptotic and necrotic cells. As exosomes (small EV) express “eat-me” signals such as phosphatidyl-serine, it is likely that they are cleared similar to dead cells. Here we discuss measures that cancer cells have developed to protect their EVs from rapid depletion. The expression of “don’t eat me” signals such as CD47 and CD24 on the tumor cell surface and in released exosomes is of vital importance. We will focus on the role of the CD24-Siglec-10 binding axis as a stop signal at the interface between tumor cells and phagocytic cells. Extending the lifetime of EVs is essential for the cancer to achieve systemic immune suppression and to prepare metastatic niches for spreading. Keywords: CD24, CD47, Extracellular vesicles, Siglecs, carbohydrates, phagocytosis

scholarly journals STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III

1936 ◽  
Vol 64 (1) ◽  
pp. 7-18 ◽  
Author(s):  
John F. Enders ◽  
Morris F. Shaffer
Keyword(s):  
Natural Immunity ◽  
Type Iii ◽  
Pneumococcus Type

1. A correlation appears to exist between the failure of certain strains of Pneumococcus Type III to grow at 41°C. and their lack of virulence for rabbits. 2. It is likely that the capacity to grow at 41°C.—an attribute constantly but not exclusively associated with strains of Pneumococcus Type III virulent for rabbits—is a prerequisite, but not the sole factor, in determining their virulence for these animals.

scholarly journals ІМУНОЛОГІЧНІ АСПЕКТИ ГЕНЕРАЛІЗОВАНОГО ПАРОДОНТИТУ (ОГЛЯД ЛІТЕРАТУРИ)

2018 ◽  
Author(s):  
N. M. Saveleva
Keyword(s):  
Defense Mechanisms ◽  
The State ◽  
The Body ◽  
Human Immune System ◽  
Phagocytic Cells ◽  
Effective Prevention ◽  
Close Relationship ◽  
Analytical Review ◽  
Autoimmune Processes ◽  
Somatic Diseases

The article presents the results of an analytical review of literature data in the field of assessing the state of immunological indicators in patients with generalized periodontitis. These data indicate a close relationship between the state of the human immune system and the development of generalized periodontitis against the background of concomitant somatic diseases. The influence of periodontopathogenic microorganisms on the immune response of a macroorganism is described. Data on the state of local and systemic immunity of patients with generalized periodontitis, abnormalities in antibody formation and the functioning of cellular defense mechanisms, activity and content of phagocytic cells, T-lymphocytes, natural killers, imbalance in the cytokine system in the gums and peripheral blood are presented. A number of authors note a significant role in the development of generalized periodontitis secondary immunodeficiency, allergic reactions and autoimmune processes, the general state of the adaptive mechanisms of the body. Disclosure or deepening of knowledge about the pathogenesis of generalized periodontitis will allow to construct optimal adequate therapy and offer effective prevention of dental disease.

scholarly journals Through the Open Window: How Does the Brain Talk to the Body?

2021 ◽  
Vol 9 ◽  
Author(s):  
Ludmila Gordon ◽  
Gil Levkowitz
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Blood Stream ◽  
The State ◽  
The Body ◽  
Brain Cells ◽  
Open Window ◽  
Food Digestion ◽  
The Brain ◽  
Sleep Cycles

The brain controls the activities of the body, including food digestion, drinking, sleep cycles, temperature, blood pressure, and more. These functions are essential to keep the body in homeostasis, which is the state of being steady and balanced. To control homeostasis, the brain talks to the body with the help of chemical messengers called hormones. Hormones travel through the blood stream from the brain to the body and back. However, in order to protect the delicate brain cells from unwanted intrusions, the blood vessels of the brain are tightly sealed, preventing the passage of most molecules. How, then, does the brain bypass this barrier to communicate with the body? The answer is that, in certain parts of the brain, the blood vessels contain special window-like openings that allow passage of hormones. Scientists are investigating why and how some blood vessels open their windows while others remain sealed.

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