Of all the arachidonic acid metabolites, only prostaglandin E (PGE) has been shown to have a clear role in the regulation of cellular and humoral immune responses. In cellular immune responses such as T cell proliferation, lymphokine production, and cytotoxicity, PGE usually acts as a feedback inhibor of the response. This is also true of macrophage and natural killer cytotoxicity. In some instances PGE is responsible for cellular activation rather than inhibition. This is clearest in the control of humoral immunity, where PGE production is a necessary component in the generation of some type of T suppressor cells. Disturbances in immune function found in several human conditions and diseases have been linked to changes in PGE mediated immunoregulation. Either increased production of PGE or increased sensitivity to PGE results in depressed cellular immunity. Conversely drugs which inhibit PGE production act as stimulants of cellular immune functionin vitro andin vivo.

Regulation of the immune response by prostaglandins

MACROPHAGES play a central and essential part in the immune response by presenting antigen to lymphocytes during the development of specific immunity and by serving as supportive, "accessory" cells...

Current concepts: immunology. Monocytes and macrophages.

The immunology of mycobacterial diseases.

Disease due to Mycobacterium avium-intracellulare.

The most important immunopathological consequence of experimental mycobacterial infection is the suppression of T cell-mediated immune response to both mitogens and mycobacterial antigens. We registered that there was decreased concanavalin A-induced spleen cell proliferation in infected susceptible BALB/c mice as compared to normal mice. In resistant (C3H/HeJ) mice, infection with the bacteria did not induce any suppression in the mitogen-induced lymphoproliferation. Likewise, delayed-type hypersensitivity (DTH) responses, to keyhole limpet hemocyanin and mycobacterial crude soluble antigen were suppressed in infected BALB/c mice but not in C3H/HeJ mice. This depressed T helper cell function may either be due to defective T cell-receptor occupancy by antigen-Ia complex or altered co-stimulatory signals provided by antigen-presenting cells. In the present study, we have investigated the status of certain co-stimulatory molecules on the infected macrophages from both susceptible and resistant mice. Our results demonstrate that upon mycobacterial infection, the macrophages are rendered incapable of delivering the co-stimulatory signals to T helper cells, possibly due to the involvement of prostaglandin, as inhibition of its biosynthesis by indomethacin reversed the defect. Furthermore, the selective regulation was bacteria-induced as killing of the bacteria by rifampicin abrogated the derangements in the expression of co-stimulatory molecules on the Mycobacterium-infected macrophages. Our observations revealed that upon infection with Mycobacterium tuberculosis, B7 was down-regulated while ICAM-1 was increased only in BALB/c but not in C3H/HeJ mice. Expression of VCAM-1 did not change during the infection in either strain of mice. We found that these changes in ICAM-1 and B7 expression on the surface of infected macrophages resulted in inhibition of DTH-mediating functions of T helper cells from BALB/c mice. The results obtained in this study describe not only a novel immune evasion strategy adopted by Mycobacterium, but also open up the possibility of immunotherapy of mycobacterial infection by selective manipulation of co-stimulatory molecules.

Macrophage-T cell interaction in experimental mycobacterial infection. Selective regulation of co-stimulatory molecules on Mycobacterium-infected macrophages and its implication in the suppression of cell-mediated immune response.

Indomethacin-responsive mononuclear cell dysfunction in “atypical” mycobacteriosis

The purpose of this article is to highlight past and prospective uses of dialyzable leukocyte extract (DLE) containing transfer factor (TF) in veterinary medicine. In addition, the current state of knowledge concerning TF in comparative studies is presented. Recent review articles on TF in domestic animals should be referred to for additional details ( 1 , 2 , 3 ).

Dialyzable leukocyte extract containing transfer factor–its future in veterinary medicine

Immune regulators in transfer factor : [proceedings]

Publisher Summary In addition to antigen specific activities such as conversion of delayed-type hypersensitivity responses and induction of antigen-sensitive lymphocytes that produce lymphokines, crude leukocyte dialysates contain substances that have antigen-independent or nonspecific effects on immunologic and inflammatory responses Several of these effects such as enhancement of recovery of the rosette-forming property of trypsin-treated T-lymphocytes; increases in the percentage of circulating T-lymphocytes in immunologically deficient patients; induction of cortisone resistance in thymocytes; accumulation of cyclic guanosine monophosphate in mononuclear leukocytes; and enhancement of T-cell responses to mitogens have also been attributed to thymic hormones Leukocyte dialysates from human and murine cells contain significant amounts of thymosin α 1 -like immunoreactive material This material could be related to some of the nonspecific and antigen-independent effects of leukocyte dialysates on modulation of immunologie and inflammatory reactions

THYMOSINα 1-LIKE MATERIAL IN DIALYSATES OF LEUKOCYTE EXTRACTS

Although chemotherapy of tuberculosis has resulted in a dramatic decrease in the number of new and active cases in the United States, relatively little improvement has been made in the treatment of diseases caused by nontuberculous mycobacteria. Depending on the type of hospital and population served by the hospital, the incidence of “atypical” mycobacteria may be as high as 30% of all mycobacterial infections (1). Aside from the clinical importance and economic consequences of these infections, these chronically ill patients provide a valuable source of new information concerning cellular defense mechanisms and resistance to chronic infectious diseases. Unlike patients with chronic fungal infections who commonly develop disease during early childhood, patients with “atypical” mycobacterial diseases are usually well during early childhood and adolescence (2). Thus, to explain the predisposition of individuals to infections with these organisms, one would predict an abnormality of immunoregulatory mechanisms rather than a failure to develop immunocompetent lymphoid cells.

Charles H. Kirkpatrick

Papers

Indomethacin-responsive mononuclear cell dysfunction in “atypical” mycobacteriosis

Dialyzable leukocyte extract containing transfer factor–its future in veterinary medicine

Immune regulators in transfer factor : [proceedings]

THYMOSINα 1-LIKE MATERIAL IN DIALYSATES OF LEUKOCYTE EXTRACTS

Improvement of Abnormal Lymphocyte Responses in “Atypical” Mycobacteriosis with Indomethacin