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Biomedical subjects

D Befus

Publications and source records attributed to D Befus.

54 records · Page 3Linked to original sources
PubMed1986

Immunity in intestinal helminth infections: present concepts, future directions.

Although intestinal helminth and protozoan infections are prevalent throughout the world, their impact is poorly known. Nevertheless, the morbidity and mortality that occur have stimulated research into host resistance and pathogenesis. Unfortunately, despite an increasing knowledge base, the actual effector molecules which lead to parasite loss are unknown. IgA antibody, intraepithelial leukocytes and mucosal mast cells are thought to be involved. The role of these and other responses in making the intestinal microenvironment hostile to the parasite through effects of neurotransmission, epithelial cell differentiation and function, smooth muscle activities, and local inflammatory responses must be studied. Future research will include: further definition of the cellular and molecular immunologic repertoire of the intestine, identification of local effector molecules and investigation of interactions between antigen-specific immune responses and intestinal physiology. Studies of human infections will be more restricted but must include: assessment of parasite-specific local immunologic responses, inflammatory events in the intestine, and development of relatively non-invasive techniques to study gastrointestinal physiology during parasitic infection. Perhaps most importantly, research facilities must be established in developing countries to investigate intestinal immunological, inflammatory and physiological responses during infection. Through such investigations, risk factors for susceptibility and disease severity may be identified and therapeutic or prophylactic strategies developed.

Animals↗
PubMed1986

Unique characteristics of local responses in host resistance to mucosal parasitic infections.

Because of the tremendous impact that parasitic infections have on the health and productivity of humans and domestic animals, considerable research effort has been focused upon understanding the mechanisms of host-parasite coexistence, host resistance and immunopathology. Studies have employed a range of approaches including: kinetic analysis of parasite establishment, development, fecundity and survival in naive and previously-infected hosts; correlation between parasite survival and histopathologic responses at the site of infection; vaccination with attenuated parasites or their products; cellular and serum transfer of immunity to naive or immunocompromised hosts; pharmacologic manipulation of potential mediators of host defense using agonistic and antagonistic drugs. However, it is becoming increasingly clear that to understand the mechanisms associated with host resistance and parasite survival, one must define the characteristics of the local microenvironment at the host-parasite interface. One of the approaches by which such studies can be made involves the isolation and characterization of cells derived from the local infection site. This manuscript reviews some of these studies on local aspects of mucosal immune responses in parasitic infections. Examples that will be discussed include IgA antibody, intraepithelial leukocytes from the intestine, intestinal mast cell populations, macrophages derived from bronchoalveolar lavage, and local immunoregulatory responses during respiratory and intestinal parasitic infection. These studies have established unequivocally that local responses to mucosal parasitic infection can only be appropriately investigated using cells derived from the specific microenvironment. This conclusion should encourage others to further study these local responses and to be innovative in investigating unexplored aspects of the host-parasite interface.

Animals↗
PubMed1986

Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen.

We examined the effect of vasoactive intestinal peptide, substance P, and somatostatin on concanavalin A (1 microgram/ml)-induced lymphocyte proliferation and immunoglobulin (IgA, IgM, and IgG) synthesis by cells from spleens, Peyer's patches, and mesenteric lymph nodes. These neuropeptides (10(-7) to 10(-12) M) modulated immune responses in a dose-dependent manner. For a comparative study, neuropeptides were used at 10(-8) M concentration. Both vasoactive intestinal peptide and somatostatin significantly decreased DNA synthesis (30 to 50%), whereas substance P increased synthesis (40%) in lymphocytes from all organs tested. IgA synthesis was significantly altered by all of the neuropeptides tested, whereas IgM synthesis was less affected and IgG synthesis was virtually unchanged. Somatostatin inhibited IgA (20 to 50%) and IgM (10 to 30%) synthesis in lymphocytes from all three organs. Substance P increased IgA synthesis in mesenteric lymph nodes (50%), spleens (70%), and Peyer's patches (300%). It also increased IgM synthesis in Peyer's patches (20%) and spleens (30%), but was without effect on IgM synthesis in mesenteric lymph nodes. Vasoactive intestinal peptide increased the IgA response in mesenteric lymph nodes (20%) and spleens (30%), but inhibited IgA synthesis in lymphocytes from Peyer's patches (60%). Interestingly, in Peyer's patches, IgM synthesis was increased by vasoactive intestinal peptide (80%), whereas it was unchanged in mesenteric lymph nodes and spleen. Thus, not only did these neuropeptides have different effects on the production of different immunoglobulin isotypes, but their effect was also organ-specific. Because neuropeptides which are abundant in the intestine can modulate IgA and other immunoglobulin synthesis in vitro, they may play a significant regulatory role in mucosal immune responses in vivo.

Animals↗
PubMed1986

Peripheral blood basophils, basophil progenitors, and nasal metachromatic cells in allergic rhinitis.

Relationships among mature blood basophils, blood basophil colony-forming units in culture (CFU-c), and nasal metachromatic cells (NMC) were investigated using hemopoietic and histochemical techniques in 29 patients with allergic rhinitis and in 7 nonatopic control subjects. Total blood granulocyte and basophil CFU-c were significantly elevated in atopy; the highest levels of basophil CFU-c were found in patients with low total NMC counts in nasal scrapings (Group I), compared with those with intermediate (Group II) or high (Group III) counts: 10 +/- 3 basophil CFU-c per 10(6) cells in 10 Group I patients, 4 +/- 2 in 10 Group II patients, 3 +/- 1 in 9 Group III patients, and 0.1 +/- 0.1 in nonatopic control subjects (p less than 0.05). Mean histamine content and frequency of histamine-positive granulocyte colonies correlated with counts of basophils in colonies (r = 0.864, p less than 0.001). Peripheral blood basophils, which stained metachromatically with toluidine blue at pH 0.5 after Mota's lead acetate but not after formalin fixation, were highest in atopic Group III and lowest in Group I; a similar relationship was observed only for NMC, which also failed to stain after formalin fixation. Metachromatic cells in colonies were similar to formalin-sensitive NMC and to peripheral blood basophils in their sensitivity to different fixatives. Nasal symptoms correlated inversely with the number of basophil CFU and directly with the number of either formalin-sensitive NMC or peripheral blood basophils. These findings confirm and extend evidence for increased nasal metachromatic cells, basophilia, and alterations in basophilopoiesis in atopy.

Adolescent↗
PubMed1985

Heterogeneity of metachromatic cells in human nose: significance of mucosal mast cells.

The distribution and abundance of histochemically and morphologically distinct subpopulations of metachromatic cells were investigated in nasal secretions and scrapings from patients with allergic rhinitis, as well as in nasal biopsy specimens from other patients. These analyses of the metachromatic cells demonstrate that basophils and two distinct mast cell populations are present in nasal specimens. One mast cell subpopulation was analogous to the atypical mucosal mast cell of the rat and human intestine, whereas the other cell population was similar to the typical connective tissue mast cell type. In nasal scrapings greater than 80% of the metachromatic cells was mast cells, almost exclusively of the atypical "mucosal" type. However, basophils were the predominant metachromatic cell type in nasal secretions, and atypical mast cells were more abundant than typical mast cells. Few basophils were observed in biopsy specimens, but mast cells were widely distributed in various anatomic compartments. Atypical mast cells outnumbered the typical type in the epithelium and lamina propria, whereas the reverse was true in the submucosa. When the number and type of metachromatic cell in scrapings were analyzed in relation to clinical findings, there was a significant correlation with severity of symptomatology and nasal swelling and pallor. Atypical "mucosal" mast cells were the major cell type in all specimens, from those with mild to those with severe clinical findings. When the distinct spectrum of responsiveness to antiallergic compounds of atypical mast cells is considered, these observations have important therapeutic implications.

Adolescent↗
PubMed1985

Mast cell heterogeneity in man. I. Histologic studies of the intestine.

We have studied the distribution and abundance of histochemically distinct mast cell subpopulations in the normal small and large intestine of man. One subpopulation has histochemical properties similar to the functionally distinct intestinal mucosal mast cell (MMC) of the rat and the other has properties similar to the widely distributed mast cell found in connective tissues and the peritoneal cavity of many animals. Both subpopulations are present in intestinal epithelium, lamina propria, submucosa and muscularis mucosa, and muscle. However, the subpopulation histochemically similar to the rodent MMC is significantly more abundant than the other in all sites in the large intestine and also in the lamina propria and muscle of the small intestine. It is important to determine whether these histochemically distinct mast cell subpopulations in man differ in their responses to various secretagogues and antiallergic compounds as in the rat.

Cell Count↗
PubMed1985

Mast cell heterogeneity: effects of neuroenteric peptides on histamine release.

Recent reports suggesting that the actions of certain neuroenteric peptides may be mediated in part by the secretion of histamine and other mast cell contents could have important implications for gastrointestinal motility and secretion. However, evidence for a mast cell-hormonal interaction is based on studies using peritoneal or cutaneous mast cells. Because intestinal mucosal mast cells (MMC) differ functionally from peritoneal mast cells (PMC), we compared the effects of several neurotransmitters and intestinal hormones on histamine secretion from two mast cell types in the rat. MMC hyperplasia was induced in rats by infection with the nematode Nippostrongylus brasiliensis, and MMC were isolated from the small intestine by collagenase digestion. Substance P, somatostatin, vasoactive intestinal polypeptide (VIP), neurotensin, and bradykinin had a potent secretagogue effect on (10(-7) to 10(-4)M) PMC which was temperature-, energy-, and calcium-dependent. In contrast to PMC, MMC released significant amounts of histamine only when challenged with substance P. Acetylcholine, bombesin, motilin, and pentagastrin had no secretory effect on either PMC or MMC. The differences between PMC and MMC in responsiveness to peptides could not be attributed to the MMC isolation procedure because PMC treated similarly or mixed with MMC suspensions retained their responsiveness to these stimuli. Our results extend the concept of neurocrine control of mast cell function, but indicate that mast cells from different sites have distinct profiles of responsiveness to regulatory peptides.

Animals↗
PubMed1984

Gut- and bronchus-associated lymphoid tissue.

Bronchus-associated and gut-associated lymphoid tissues (BALT and GALT) have both functional and morphologic similarities and are involved in seeding lung, gut, and other mucosal sites with predominantly IgA-containing B cells. Both types of lymphoid tissue are engaged in the regulation and the controlled amplification of immune responses, which vary from positive mucosal responses in both mucosae and peripheral tissues to local mucosal responses and systemic tolerance. Their further involvement in provision of cells destined to reside in the epithelial compartment of the body appears likely but requires further investigation. Their role in the provision of precursors of mucosal mast cells must also be explored further, but some participation in this event appears likely. The mucosa-associated lymphoid tissue (MALT) system appears to be integrated with the systemic immune system but may be considered as separate from it in several functional ways.

Animals↗
PubMed1984

Broncho-alveolar leucocyte responses during primary and secondary Nippostrongylus brasiliensis infection in the rat.

Using broncho-alveolar lavage, we have studied the cellular responses in the rat lung following primary and secondary infection with Nippostrongylus brasiliensis. During the primary infection, there was a biphasic increase in total broncho-alveolar leucocytes and in the absolute numbers of macrophages, neutrophils, eosinophils and lymphocytes. The first peak occurred on days 4-6, and the second peak occurred around day 16, after infection. During the secondary infection there was an anamnestic-like response by all cell types. These data suggest that the broncho-alveolar leucocyte responses to infection have an immunological basis and that in addition to the alveolar macrophage, neutrophils, eosinophils and lymphocytes may play a significant role in lung resistance against migrating helminth larvae.

Animals↗
PubMed1984

Mast cell heterogeneity and hyperplasia in bleomycin-induced pulmonary fibrosis of rats.

The distribution, density, and histochemical subtype of mast cells were studied in the respiratory tract of rats with bleomycin-induced pulmonary fibrosis. In normal rats, mast cell densities were highest in the trachea and lowest in the bronchus and parenchyma. Two histochemically distinct mast cell populations were identified in the mucosa adjacent to the tracheal cartilage, but elsewhere only a single population of typical connective tissuelike mast cells was found. After intratracheally administered bleomycin, lung histamine levels (micrograms/g wet weight) increased as much as 14-fold by Day 50. Pulmonary mast cell changes were present early in the fibrotic process, and by Day 14 the mast cell density in the parenchyma was 10 times normal. These parenchymal mast cells were histochemically of the connective tissue type. Thus, pronounced mast cell hyperplasia occurs during the evolution of experimental pulmonary fibrosis. This model provides a powerful tool to study pulmonary mast cells and to identify their role in fibrotic disease.

Animals↗
PubMed1984

Expression of IgE receptors and histamine in cloned natural killer cell lines.

Natural killer (NK) activity is mediated by large granulated lymphocytes (LGL). Recently, the relationship of NK cells to mast cells and basophils has been suggested. We therefore examined three distinct interleukin 2-dependent cloned cell lines capable of mediating NK lysis. Virtually all the cells of each line contained membrane-bound granules. Interestingly, ultrastructural studies demonstrated that the granules in each cell line were morphologically distinct and thus heterogeneous. All three cloned, granulated NK cell lines were found to variably express low numbers (less than or equal to 1.3 X 10(4)) of low affinity plasma membrane IgE receptors (Fc epsilon R). In contrast to mast cells and basophils, however, none were found to express high numbers of high affinity Fc epsilon R. In addition, none of the three NK cell lines were found to contain histaminase-sensitive histamine. Our results suggest that NK cells are not related to mast cells or basophils.

Animals↗
PubMed1984

Complement-dependent killing of Nippostrongylus brasiliensis infective larvae by rat alveolar macrophages.

Histopathological studies have provided circumstantial evidence that helminth parasite destruction occurs in the lung; however controlled in vitro studies on the helminthocidal activity of lung cells have not been reported. This study presents evidence that Nippostrongylus brasiliensis infection in the rat induces alterations in broncho-alveolar lavage (BAL) cell numbers, differential counts, and in vitro helminthocidal activity. Normal, uninfected rats yielded 3.3 +/- 0.6 X 10(6) BAL cells/rat, consisting predominantly of alveolar macrophages (greater than 90%). However on days 2-8 post-infection there was a 1.5-2.4-fold increase in BAL cell numbers with a significant neutrophilia on day 2 and a significant increase in the absolute number of all cell types on day 8. On day 32 post-infection, BAL cell numbers had returned to control levels. Normal BAL cells neither adhered to nor killed N. brasiliensis infective larvae (L3) in the presence of rat complement. By contrast BAL cells recovered from infected rats on days, 2, 8 or 32 post-infection (D2, D8 and D32 BAL cells, respectively) adhered under similar conditions. However, only D8 and D32 BAL cells killed L3. This complement-dependent killing correlated with significantly increased numbers of C3 receptor bearing alveolar macrophages in D8 and D32 BAL cells. Complement-dependent alveolar macrophage helminthocidal activity may therefore play an important role in lung resistance against resident or migrating helminths.

Animals↗
PubMed1983

Regulation of lymphoblast traffic and localization in mucosal tissues, with emphasis on IgA.

A fundamentally important factor in the expression of immunity at mucosal sites is the migration of primed lymphocytes to, from, and among mucosal tissues. Despite considerable information in recent years on the selective localization of B lymphoblasts, especially those destined to make IgA antibodies in mucosal tissues, the basis for this remains obscure. Several cell-associated factors such as surface characteristics, histo-compatibility type, and organ derivation of the cells play a significant role for T and B lymphoblast localization. Factors that regulate lymphoblast delivery to tissues, such as blood flow, or control emigration from tissues, such as arachidonic acid metabolites, are discussed. Finally, factors such as the presence or absence of high endothelial venules, isotype-specific T helper cells, sex hormones, antigen, macrophages, and iron all may play a significant role in mucosal lymphoblast localization.

Animals↗