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|Title:||Studies of the Cellular Basis of Immunity at Mucosal Surfaces|
|Authors:||McDermott, Rundle Mark|
|Keywords:||Medical Sciences;Medical Sciences|
|Abstract:||<p>The origins of the immunoglobulin-containing cells in the intestinal, respiratory, mammary, and genital tissues were studied in mice, rats, and guinea pigs by using an adoptive lymphocyte transfer method. Proliferating lymphocytes (lymphoblasts) were obtained from various donor lymphoid sources and radiolabelled in vitro with either ³H-thymidine or ¹²⁵-deoxyuridine. Radiolabelled lymphoblasts were then injected into the circulation of recipient animals. Twenty-two - 24 h later, various tissues taken from recipient animals were examined for the presence of radiolabelled donor cells by either radiocounting or autoradiographic techniques. Furthermore, radiolabolled B-cells containing different immunoglobulin isotypes were identified in mouse tissues by a combination of immunofluorescent staining with autoradiographic procedures. It was found possible to greatly accelerate this procedure by the use of liquid scintillation fluid so that ³H-thymidine-labelled cells could be identified in less than 24 h as opposed to 4-6 wks in the absence of scintillation fluid.</p> <p>In mice and rats, mesenteric lymph node (MLN) lymphoblasts showed a propensity to selectively localize in the cut mucosa. Careful examination of other mouse tissues revealed that MLN lymphoblasts were present, not only in the intestinal lamina propria, but also beneath the mucosal epithelia of the respiratory and genital tracts, the mammary glands and in the MLN. In these mucosal tissues approximately 60% of these cells contained IgA and 25% contained IgG. In peripheral lymph noded (PLN), a few labelled MLN cells were observed and 40% of these contained IgG, whereas only 8% were of tho IgA isotype. The preference of MLN to populate mucosal sites was clear from the results.</p> <p>In marked contrast, when labelled PLN cells were adoptively transferred, the majority returned to their sites of origin and contained IgG. Of the small number of labelled PLN cells found in mucosal tissues, approximately equal percontages (30%) of IgA- and IgG-containing cells were soon.</p> <p>Dividing cells prepared from bronchial (mediastinal) lymph nodes (BLN) showed a propensity to localize in the lungs rather than in the intestine or lymph nodes. However, tho predominant immunoglobulin content of these donor cells in tho gut, lungs, and MLN was IgA. Thus, the BLN made a quantitatively minor, but presumably significant, contribution to the IgA plasmacytes found in the gut lamina propria; in the lungs, BLN made a quantitatively major contribution to population of IgA-containing cells residing in the lung mucosa.</p> <p>It was concluded that, in rodents, the MLN was a major contributor of the immunoglobulin-containing celIs beneath the mucosal epithelia of the gut, lungs, cervix, and vagina and gestational mammary glands. Thus, lymph nodes draining two mucosal surfaces, though differing in IgA plasmacyte precursor content, both possessed cells destained to localize in mucosal tissues. Furthermore, there was organ specificity for the distribution of these cells; those immediately derived from the lymph nodes draining the bowel tended to return to the bowel, whereas those from the lungs tended to return to the lungs.</p> <p>To further explore the properties of MLN lymphoblasta, the influence of the mouse estrous cycle on MLN lymphoblast localization in the cervix and vagina was investigated. Compared to proestrus and estrus, a 2-fold reduction in the number of MLN lymphoblasts localizing in the diestral cervix and vagina was observed. Detection of the immunoglobulin isotype of these cells suggested that this reduction was restricted to the IgA plasmacyte progenitor population, i.e., the major B-lymphocyte subpopulation entering these sites. No significant changes in B-lymphoblast subpopulation lodging in the small intestine were observed over the course of the estrous cycle. Moreover, although the small intestine more than doubled in wet weight by late gestation, this increased quantity of gut tissue did not appear to compete for a finite number of donor MLN lymphoblasts. It was concluded that changes in the sex hormone status of mice may influence selective localization of MLN lymphoblasts in sex hormone target tissues.</p> <p>Since subpopulations of cells can often be separated from each other on the basis of cell size, some preliminary studies were done to purify, on the basis of size, subpopulations of mouse MLN lyphoblasts. These results indicated that the labelled cells being transferred were all large in size, likely lymphoblasts, and that it was possible to use this technique to obtain donor cell populations highly enriched in the proportion of labelled cells. Some evidence was obtained to suggest that the MLN contained a minor population of lymphoblasta with a propensity to localize in the spleen.</p> <p>To examine the possibility that some lymphocytes in the gut mucosa may themselves have a predisposition to localize in other mucosal tissues (assuming that they were able to migrate), lymphocytes were mechanically prepared from the lamina propria of the guinea pig small intestine. A subpopulation of these cells incorporated ¹²⁵I-deoxyuridine and localized (within 24 h after adoptive transfer) in the gut mucosa in a manner similar to transferred MLN lymphoblasts and different from either PLN or Peyer's patch lymphoblasts. It was concluded that a portion of the lymphocytes seen in the gut mucosa were similar in migration characteristics to cells found in the MLN.</p> <p>The results of these studies support the concept of a common mucosal immunologic system in which different mucosal surfaces are linked by migrating IgA plasmacyte precursors originating primarily in the lymphoid tissue associated with the intestinal and respiratory tracts. s of these studies support the concept of a which different mucosal surfaces migrating IgA plasmacyte precursors originating primarily in the lymphoid tissue associated with the intestinal and respiratory tracts.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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