scholarly journals STUDIES ON THE MECHANISM OF IMMUNITY IN TUBERCULOSIS

1939 ◽  
Vol 69 (4) ◽  
pp. 579-599 ◽  
Author(s):  
Max B. Lurie

1. Tuberculous and vaccinated rabbits and guinea pigs mobilize mononuclear phagocytes at the site of a non-specific inflammation with greater rapidity than do normal animals, just as they respond to tubercle bacilli. 2. The succession of cells that characterizes inflammation in general is accelerated in allergic rabbits and guinea pigs in response to non specific irritants. 3. The pH at the site of reinfection with tubercie bacffli in immun ized rabbits and guinea pigs and at the site of a non-specific inflammation in the latter is slightly lower than in a similar site in a normal animal. 4. No constant relation was found between the mobifization of mononuclears and the hydrogen ion concentration at the site of inflammation. 5. The rate of mitotic and amitotic division of mononuclears in allergic rabbits and guinea pigs in response to non-specific irritants is greater than in normal animals. 6. Mononuclears derived from actively tuberculous or vaccinated guinea pigs exhibit greater in vitro phagocytic capacity for carbon particles than mononuclears obtained from normal animals. 7. Mononuclears of tuberculous rabbits ingest more staphylococci than the phagocytes of the same type originating from normal animals. 8. Mononuclears originating from actively tuberculous rabbits and guinea pigs exhibit greater in vitro phagocytic capacity for tuberde bacilli than mononuclears obtained from normal animals. 9. The enhancement of the phagocytic capacity for tubercie bacilli afforded mononuclears by vaccination with a bacillus of low virulence is lower, and of questionable significance. 10. The increased phagocytic activity of mononuclears derived from tuberculous or vaccinated rabbits and guinea pigs for tubercie bacilli and for non-specific particulate matter occurs in media containing sera derived from normal and from tuberculous individuals. 11. The more rapid mobilization of mononuclears by immunized animals in response to specific as well as non-specific irritants is associated with their increased physiological activity. The significance of this enhanced activity conferred by the tuberculous process on the mesenchyme cells is discussed in relation to the mechanism of immunity to tuberculosis and other phenomena.

1953 ◽  
Vol 97 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Emanuel Suter

When monocytes derived from normal guinea pigs or rabbits were infected with tubercle bacilli and cultivated in vitro, the bacilli multiplied abundantly within the cytoplasm of these cells. By contrast, intracellular multiplication of the bacilli was retarded or completely inhibited within the monocytes of rabbits or guinea pigs vaccinated with BCG. This inhibition of growth was observed with both virulent or attenuated strains of tubercle bacilli. Under the conditions used in the present study, the ability of monocytes to inhibit bacillary proliferation was the same whether serum from a normal animal or from vaccinated animals was used in the tissue culture medium. Moreover, the serum of vaccinated animals did not inhibit multiplication of tubercle bacilli within monocytes derived from a normal animal. The ability of guinea pig monocytes to interfere with intracellular bacillary proliferation was first perceptible 8 days after vaccination.


1978 ◽  
Vol 41 (2) ◽  
pp. 305-321 ◽  
Author(s):  
W. A. Weems ◽  
J. H. Szurszewski

1. In vitro studies were conducted on neurons within the inferior mesenteric ganglion (IMG) of guinea pigs to investigate how intrinsic features of the spike-generating process interact with preganglionic inputs to produce the output firing patterns of these neurons. Intracellular-electrode techniques were used to monitor and control electrical activity of IMG neurons. Preganglionic inputs were activated either synchronously by stimulating an attached nerve trunk or asynchronously by leaving the ganglion attached to a segment of terminal colon and activating the colonic-IMG mechanosensory system. 2. Ninety-seven percent of the neurons studied demonstrated an afterspike hyperpolarization (ASH). The ASH process was activated only by the occurrence of a spike and did not have a synaptically induced component. Further activation of this process was produced by two or more spikes having interspike intervals less than the duration of an ASH following a single spike. An aftertrain hyperpolarization (ATH) resulted from this progressive activation. The amplitude of both the ASH and the ATH decreased when the resting membrane potential was hyperpolarized by current injection or by increasing the external potassium ion concentration. 3. Neuronal excitability was reduced during the ASH. From this observation it was concluded that when IMG neurons operate in the occasional-firing mode, the ASH process prevents output frequency from greatly exceeding the reciprocal of the ASH duration produced by a single spike. 4. Two types of synaptically induced slow depolarizations were observed: a slow, long-latency depolarization and a short-latency depolarization (SLD). These depolarizations differed in their latency, onset, and duration. Both were capable of converting synchronous, preganglionic input from subthreshold (non-spike-activating) to threshold (spike-activating) activity. 5. Neurons having resting potentials more positive than -60 mV were capable of firing in the rhythmic-firing mode; 40% of these neurons demonstrated tonic- and 60% phasic-firing behavior. Frequency-current relations for tonic-discharging neurons were linear from the rhythmic-firing threshold to current levels approximately 2.5 times the threshold value. Minimal frequency for tonic firing and the slope of the linear portion of the frequency-current relation were indirectly related to the duration of the ASH. 6. This study suggests that sympathetic, noradrenergic neurons of the IMG can operate in either the occasional- or rhythmic-firing mode. In the physiologic state in vivo, most IMG neurons probably do not produce action potentials in excess of 10-15 Hz because of their intrinsic properties which regulate firing in both modes of operation.


2001 ◽  
Vol 281 (2) ◽  
pp. G371-G374 ◽  
Author(s):  
Linzi A. Thomas ◽  
Martin J. Veysey ◽  
Gerard M. Murphy ◽  
R. Hermon Dowling

Prolonged large bowel transit time and an associated increase in the proportion of deoxycholic acid (DCA) in serum and bile have been implicated in the development of cholesterol-rich gallstones and colon cancer. Prolongation of intestinal transit also increases intracolonic pH that, we hypothesized, should favor the solubilization and absorption of newly formed DCA within the colon. To test this hypothesis, we performed in vitro studies on homogenized cecal aspirates (obtained at colonoscopy) that were incubated anaerobically with [14C]cholic acid for 16 h after which the pH was adjusted to between 4.0 and 7.0 in 0.5-pH unit steps. The resultant reaction mixtures were centrifuged to separate the supernatant from the precipitate, and the specific activity of [14C]DCA was quantitated in both phases. As the pH in the aspirates was manipulated from 4.0 to 7.0, the proportion of newly formed, labeled DCA increased in the supernatant and fell in the precipitate, particularly at a hydrogen ion concentration of <100 × 10−7 (equivalent to pH 5.0–7.0). These results show that the solubility of DCA in colonic contents increases with increasing pH. If solubility is rate limiting, this should lead to increased absorption that, in turn, would explain why the proportion of DCA in serum and bile increases with the prolongation of large bowel transit time.


1963 ◽  
Vol 204 (6) ◽  
pp. 1048-1054 ◽  
Author(s):  
Ronald B. Miller ◽  
Ian Tyson ◽  
Arnold S. Relman

Intracellular pH of isolated rat diaphragm was measured with both a C14-DMO method and a tissue CO2 technique. The values for intracellular pH by each method, although slightly different, changed in parallel under most experimental conditions. Acute, severe potassium depletion in vitro had no detectable effect on intracellular pH, nor did prior depletion in vivo followed by incubation in a potassium-free bath. This was true whether or not the potassium-depleted muscle was exposed to normal or elevated extracellular levels of bicarbonate, and was unaffected by the presence of cationic amino acids in the bath. Acute repletion of previously potassium-depleted muscle resulted in a small rise in cell pH, but this was no greater than that produced by loading normal tissues with potassium. It is concluded that under the conditions of these experiments there is no evidence of intracellular acidosis in potassium-depleted skeletal muscle. Rat diaphragm can lose up to half its potassium content in vitro without detectable increase in hydrogen ion concentration.


1936 ◽  
Vol 63 (6) ◽  
pp. 923-946 ◽  
Author(s):  
Max B. Lurie

1. There is an extracellular factor which inhibits the growth of tubercle bacilli in immunized rabbits. 2. Extracellular factors localize carbon particles, trypan blue and tubercle bacilli at the site of introduction to a greater extent in the immunized than in the normal animal. 3. This greater fixation is brought about by an increase in the density and extent of the fibrin barrier formed about the focus of the immunized animal. The more pronounced in vivo agglutination of tubercle bacilli and carbon particles in the vaccinated or tuberculous rabbit also tends to immobilize them in the tissues. 4. The growth inhibitory and localizing agents are effective in the fixation of small doses on reinfection at the portal of entry. 5. With large doses on reinfection, the increased lymph flow resulting from the intensified inflammation in the immunized animal brings about a more rapid dissemination of the bacilli to the draining lymph nodes than in the normal animal. 6. The most significant factor in immunity is the increased capacity of the rapidly mobilized mononuclear phagocytes to destroy tubercle bacilli. The impotent polymorphonuclear leukocytes quickly disappear from the site of reinfection. 7. The invading bacilli that reach the draining lymph nodes of the immunized animal are retarded in multiplication or destroyed by these phagocytes. 8. Vaccination of rabbits with BCG brings into play the factors tending to immobilize the bacilli of reinfection, inhibit their growth and destroy them with a resulting significant immunity. 9. A virulent primary infection affords a greater immunity than one of low virulence and the host reactions are expressed by a quantitative increase in those immunity factors which operate in a vaccinated animal.


PEDIATRICS ◽  
1969 ◽  
Vol 43 (5) ◽  
pp. 830-832
Author(s):  
Giles F. Filley

The PAPERS of Kildeberg and Engel and of Nelson and Riegel continue what has been called, inaccurately, "The Great Transatlantic Acid-Base Debate" betsveen two schools of acid-base physiology. Historically at least, these can be called the Continental and Anglo-American Schools and their current dispute a war of words. We will sketch their beginnings, describe some of their differences, and indicate the importance of the distinction between fundamental and derived measurement. The Continental School was probably founded by Hasselbalch, who in 1916 began the apparently never-ending search for a chemical index of a "metabolic component," i.e., a number indicating the quantity of non-volatile acid added to or lost from the body-"corrected" for respiratory effects. Hasselbalch index was typical of the genre because it required exposing a blood specimen in vitro to known CO2 gas mixtures and was called a "reduced hydrogen ion concentration." His successors have tended to work meticulously in chemical laboratories, to give special names to defined magnitudes, and to incorporate these into logical formulations. One example was that of Singer and Hastings, which was based on a thoroughgoing study of blood as a physicochemical system at various states of equilibrium outside the body. Another recent and carefully developed one is that of Siggaard-Andersen. Despite this and other authors warnings, this school formulations are subject to abuse perhaps especially by those who assume that an "Astrup determination" is a substitute for clinical judgement. The other school is less systematic, its members being more often physiologists or physicians than physical chemists.


1975 ◽  
Vol 229 (2) ◽  
pp. 344-349 ◽  
Author(s):  
KM Riegle ◽  
RL Clancy

The effect of norepinephrine (NE) on the intracellular hydrogen ion concentration [H+]i of isolated rat hearts perfused with a modified Krebs-Henseleit solution (SHS) was determined. The [H+]i was calculated with the [14C]-dimethyloxazolidinedione method. Respiratory or metabolic acidosis was produced by equilibrating the KHS with 20% C02 or decreasing the [HC03-] of the KHS, respectively. Three types of experiments were carried out: 1) beta blockade--MJ 1999 (Sotalol) was added to the KHS; 2) control--no pharmacological treatment; and 3) NE-norepinephrine was added to the KHS. The effective CO2 buffer values (delta[HC03-]i/deltapHi) during respiratory acidosis were: beta blockade, 11; control, 35; and NE, 84. The production of metabolic acidosis resulted in the following [H+]i changes: beta blockade, 52 mM; control, 60 nM; and NE 7 nM. These results suggest that NE markedly attenuates the changes in [H+]i accompanying respiratory and metabolic acidosis and may account in part for previous observations that the effective C02 buffer value of cardiac muscle in vivo is greater than that in vitro.


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