Dean Befus

A Common Mucosal Immunologic System Involving the Bronchus, Breast and Bowel

The immune response of the upper respiratory tract is characterized by a predominance of secretory IgA anitbody in local secretions and IgA containing cells in the lamina propria (1). The amount of IgA which is present at various levels of the respiratory tract differs since much more IgA is found high, than low, in the respiratory tract (2). The amount of IgA relative to IgG diminishes in secretions derived from lower in the tract, so that washings derived from the alveolar spaces show a ratio of the two immunoglobulins which approximates that of serum (2).

Human Lung Mast Cells: Distribution and Abundance of Histochemically Distinct Subpopulations

Methods originally employed to demonstrate the heterogeneity of mast cells in the rat and more recently in the human intestine were used to study mast cell heterogeneity in the human bronchial mucosa and lung parenchyma. Thus, a quantitative survey of pulmonary mast cells using different fixation and staining procedures indicated that two distinct mast cell subpopulations (formalin-sensitive and formalin-resistant) are present and have distinct patterns of distribution and abundance. The findings are of potential clinical importance because histochemical heterogeneity may be a marker of functional mast cell differences in humans including differences in responsiveness to antiallergic drugs, as occurs in rats. The findings also indicate that conventional methods of fixation are likely to lead to a gross underestimation of total mast cell numbers.

Induction and Expression of Mucosal Immune Responses and Inflammation to Parasitic Infections

At least five million people die annually of gastrointestinal infection (Holmgren, 1981), and the morbidity level from such infections must be several-fold greater. In the veterinary field, an estimated 20% of pigs born in North America and Britain die before weaning of diarrheal disease caused by Escherichia coli and transmissible gastroenteritis (TGE) virus (Porter, 1979). The human and economic losses resulting from gastrointestinal infections are thus of staggering proportions; e.g., in Kenya, Ascaris lumbricoides infection, generally considered to be relatively nonpathogenic and unimportant, results in economic losses in excess of

Mast Cell Pleomorphism: Properties of Intestinal Mast Cells

5 million per year (Latham et al., 1977). Similarly depressing figures could be provided for the mortality and morbidity statistics of respiratory infections in the international community (e.g., World Health Organization Technical Report, 1980). The magnitude of the problem of mucosal infection has stimulated research directed at its solution and, given the success of vaccination programs with various infectious diseases, the potential for immunoprophylaxis is being vigorously explored.

Natural Killer (NK) Cell Activity Against Enteric Murine Coronavirus Mediated by Intestinal Leukocytes

Consistent with their nearly ubiquitous distribution throughout the body, mast cells interact with a variety of cell types and react to numerous environmental stimuli. They can be activated by macrophage (1) and T cell factors (2), by complement fragments, as well as by IgE-allergen interactions. However, mast cells are involved in more than immediate hypersensitivity reactions because under appropriate conditions their mediators play a role in cell and organismal toxicity, immunoregulation, promotion of neovascularization and fibroblast proliferation (3). Moreover, mast cells and the nervous system appear to communicate with one another, an association that implies important physiological functions. For example, intimate contact between mast cells and nerves is common (i.e., 4,5), vagus nerve stimulation enhances antigen-induced histamine release (6); and neuropeptides and endorphins degranulate mast cells (7,8). Whether mast cells activate nerves and are, therefore, engaged in bidirectional interchanges is unclear.

Spectrum of cellular immune responses in host resistance

Relatively little is known about local cell mediated immunity (CMI) in the gut and its role in resistance to enteric virus disease. Intraepithelial leukocytes (IEL), because of their location within the epithelium, may be involved in the defense of the gut mucosa against viruses. This study was initiated to assess the endogenous local CMI response of murine mucosal lymphocytes, especially IEL, to an enveloped enteric murine virus. The Yale strain of mouse hepatitis virus (MHV-Y) was chosen for these studies. MHV-Y causes diarrhea in infant mice (1) and has been shown to be highly tropic for the intestinal epithelium (2). It repucates in NCTC-1469 cells which have the H-2k phenotype (3).

Isolation and Characteristics of Small Intestinal Lamina Propria Cells from Normal and Nematode (Nippostrongylus brasiliensis)-Infected Rats

The complexity of antigen-specific and non-specific interactions involved in host resistance and pathology is unravelling at an exciting rate. Following infection, macrophage-dependent antigenic stimulation activates a diversity of T and B lymphocytes. This initiates a series of specific antibody and cellular responses which deal directly with the infectious insult and/or call in a range of other, non-specific effector cells such as macrophages, neutrophils, eosinophils, mast cells/basophils, and natural killer cells. These cells are protective through direct anti-parasite activities or by establishing a microenvironment compatible with cohabitation between host and parasite. They also amplify and modulate effector functions and facilitate repair mechanisms by activating local epithelial cells, goblet cells, smooth muscle cells, and even the nervous system. At the forefront of immunology are our efforts to dissect the chemical mediators of host protection such as tumor necrosis factor, lymphotoxin, oxidative pathways, toxic enzyme systems and phospholipid metabolites. Such chemical mediators and others including interferon and interleukins 1, 2 and 3, can be isolated, purified and studied on cloned cells to define their activities. The challenge that remains is to dissect the in vivo activities which facilitate host survival and productivity in the face of constant exposure to infectious agents.

NATURAL KILLER ACTIVITY IN MAST CELL-DEFICIENT W/WV MICE

Intestinal lamina propria (LP) cells were isolated from normal or nematode (Nippostrongylus brasiliensis)-infected rats. At certain times after infection (days 11-17), viable cell recoveries from infected rats were lower, whereas at other times (days 20-50), they were significantly greater than those from normal rats. The frequencies of lymphocytes, plasma cells, eosinophils, mast cells and macrophages from LP differed between normal and infected rats, and the histamine content did also. However, spontaneous 3H-uridine and 3H-thymidine incorporation and the number of cells with cytoplasmic immunoglobulin were similar. LP cells from normal rats were unresponsive to the mitogens phytohemagglutinin, concanavalin A and pokeweed. 125I-deoxyuridine-radiolabeled LP lymphoblasts from normal rats were widely distributed in recipients 22-24 h after transfer and showed no selective predilection to return to the intestine. The isolation procedure can be used to study intestinal LP cells from normal or diseased animals.

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

Publisher Summary This chapter discusses cell lineage of natural killer (NK) cells, which is still a matter of debate. Cells morphologically similar to large granular lymphocytes (LGL) have been found in the epithelium of the mouse small intestine, and it has been proposed that they are mast cell precursors with T-cell characteristics. In a study described in the chapter, the NK activity of splenocytes from 8-week old W/W v mice and from their littermates recognizable by their coat color was tested. LGL were observed in cell suspensions obtained from spleen and intestinal epithelium of W/W v mice. The results indicate that it is very unlikely that NK cells are mast cell precursors.