Publisher Summary This chapter discusses the role of the immune response to Leishmania, with particular reference to the cutaneous disease caused by L. major. Leishmaniasis is caused by species of the intracellular protozoan parasite belonging to the genus Leishmania. There are three main categories of leishmaniasis: cutaneous leishmaniasis (oriental sore), mucocutaneous leishmaniasis (espundia), and visceral leishmaniasis (kala-azar). In humans, infection with Leishmania results in a spectrum of disease dependent upon the species involved and the efficiency of the host's immune response to the parasite. Diagnosis of active leishmaniasis is based primarily on the demonstration of the parasite in biopsies. A skin test using a killed whole parasite preparation (leishmanin) is used as a presumptive test. Genetic regulation of leishmaniasis is discussed in reference to mouse and humans, and the concept of suppressor T cells is reviewed. The various cytokines in leishmaniasis, including interferon (IFN) γ and interleukin (IL)-4, IL-10, IL-1, and IL-2 are also discussed.

Immunology of Leishmaniasis

The acquisition and extinction of the conditioned suppression or enhancement of one or another parameter of antigen-specific and nonspecific defense system responses have been documented in different species under a variety of experimental conditions. Similarly, stressful stimulation influences antigen-specific as well as nonspecific reactions. Moreover, both conditioning and stressful stimulation exert biologically meaningful effects in the sense that they can alter the development and/or progression of what are presumed to be immunologically mediated pathophysiologic processes. These are highly reproducible phenomena that illustrate a functional relationship between the brain and the immune system. However, the extent to which one can generalize from one stressor to another or from one parameter of immunologic reactivity to another is limited. Few generalizations are possible because the direction and/or magnitude of the effects of conditioning and "stress" in modulating immune responses clearly depend on the quality and quantity of the behavioral interventions, the quality and quantity of antigenic stimulation, the temporal relationship between behavioral and antigenic stimulation, the nature of the immune response and the immune compartment in which it is measured, the time of sampling, a variety of host factors (e.g. species, strain, age, sex), and interactions among these several variables. It seems reasonable to assume that the immunologic effects of behaviorally induced neural and endocrine responses depend on (interact with) the concurrent immunologic events upon which they are superimposed. Conversely, the efficacy of immunologic defense mechanisms seems to depend on the neuroendocrine environment on which they are superimposed. We seek to determine when and what immunologic (or neuroendocrine) responses could be affected by what neuroendocrine (or immunologic) circumstances. We therefore need studies that provide a parametric analysis of the stimulus conditions, the neuroendocrine and/or immunologic state upon which they are superimposed, and the responses that are being sampled. The neural or neuroendocrine pathways involved in the behavioral alteration of immune responses are not yet known. Both conditioning and stressor-induced effects have been hypothesized to result from the action of adrenocortical steroids, opioids, and catecholamines, among others. Indeed, all of these have been implicated in the mediation of some immunologic effects observed under some experimental conditions. We assume that different conditioning and stressful environmental circumstances induce different constellations of neuroendocrine responses that constitute the milieu within which ongoing immunologic reactions and the response to immunologic signals occur.(ABSTRACT TRUNCATED AT 400 WORDS)

http://psych415.class.uic.edu/Readings/Ader,%20Conditioning%20-%20immunology,%20AnnRevPsy,%201993.pdf

Psychoneuroimmunology: Conditioning and Stress

Publisher Summary The eye offers interesting opportunities for analyzing a panorama of immunological phenomena, including organ transplantation, immunological privilege, tolerance, and autoimmunity. This chapter addresses some of the unique immunological characteristics of the eye. The goal is not to provide an exhaustive review of ocular immunology, but to focus on the curious immunological “ground rules” peculiar to this organ. The weight of evidence suggests that the immune system is carefully regulated within the eye and, to a lesser degree, at the ocular surface. The apparent ease with which corneal grafts avoid immunological recognition suggests that the cornea is endowed with unique immunological characteristics and thus possesses an immunological privilege not shared by other organ grafts. Historically, three basic hypotheses have been offered to account for the privileged existence of corneal allografts. The simplest explanation suggests that the cornea, like certain neuronal tissues, is devoid of conventional major histocompatibility complex (MHC) antigens. Studies in rats, rabbits, and mice indicate that heterotopic transplantation of corneas to subdermal graft beds leads to rapid sensitization and swift rejection of the allografts. As for the anterior chamber, the known absence of lymphatic drainage to regional lymph nodes led early investigators to propose that the privilege of the anterior chamber could be traced to the sequestration of alloantigens within this compartment. The high incidence of spontaneous neoplasms that occurs in patients suffering from immunological disorders and in transplant recipients subjected to prolonged immunosuppression is cited as evidence in support of the immune surveillance theory. It is reasonable to suspect that the same situation occurs with immunologically privileged sites, such as the anterior chamber of the eye, where immunological censorship creates an environment that is expected to thwart the induction and expression of immunological surveillance.

Immune privilege and immune regulation in the eye.

Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice

Environmental stressors are involved in the etiology of important livestock diseases, including transmissible gastroenteritis in young pigs, Newcastle's and Marek's disease in chickens and shipping fever in cattle. Unfortunately, very little research has been conducted to learn how stress alters host resistance, although it is generally assumed that the immune system of the host is affected. This paper identifies eight stressors that typically occur in modern livestock production units: heat, cold, crowding, mixing, weaning, limit-feeding, noise and restraint. All of these stressors have been shown to alter the immune system of animals. These changes in immune function may ultimately explain the physiological basis of disease-environment interactions. A thorough understanding of stress-induced changes in host resistance will also provide the scientific basis for effective prophylactic therapy. More controlled experiments are needed to learn how stress alters the susceptibility of animals to infectious and noninfectious diseases.

Stress and immune function: a bibliographic review.

A previous study (Eur. J. Immunol. 1977. 7: 714) has shown that mice injected intravenously (i.v.) with 4 x10(9) sheep red blood cells (SRBC) produce cells which suppress delayed-type hypersensitivity (DTH). These suppressor cells are theta-positive, antigen-specific and act via a soluble factor which does not bear immunoglobulin determinants (Eur. J. Immunol. 1978. 8: 168). The present paper demonstrates that these suppressor cells are inhibitable by cyclophosphamide (CY). Mice injected with graded amounts of CY two days prior to SRBC injection, showed maximum augmentation of DTH at 200 mg/kg body weight, a dose which completely suppressed the appearance of splenic plaque-forming cells (PFC) to SRBC. In contrast, lower doses of CY enhanced both DTH and PFC responses. Time course studies showed that CY inhibited the precursors of suppressor cells and had little or no effect on suppressor cells which have already encountered antigens. This was further confirmed by passive transfer studies which showed tha- suppressor cells were inhibited if CY was administered at the same time or 2 days before SRBC injection, but were not affected if CY was given after antigen stimulation. Direct evidence for the effect of CY on suppressor cells was obtained by cell fractination with a Ficoll density gradient. The denser suppressor cell population was absent from the spleens of mice treated with 200 mg/kg of CY 2 days before i.v. injection with 1 x 10(9) SRBC.

Regulation of delayed-type hypersensitivity. III. Effect of cyclophosphamide on the suppressor cells for delayed-type hypersensitivity to sheep erythrocytes in mice.

Mice injected with 1 X 10(8) sheep red blood cells (SRBC) into the footpad showed high levels of delayed-type hypersensitivity (DTH) to SRBC 4-8 days after the injection. In contrast, mice injected intravenously with 1 X 10(9) SRBC were unresponsive to DTH induction through 1 X 10(8) SRBC injected into the footpad. This suppression of DTH was maintained for at least 6 weeks and was transferable spleen, lymph node and thymus cells to normal syngeneic recipients. Bone marrow cells, on the other hand, did not contain the suppressor cells. The suppression of DTH was antigen-specific in that DTH to chicken red blood cells and contact sensitivity to 2,4-dinitrofluorobenzene was not affected. The suppressor cells were theta-positive and Ig-negative. They appeared in the spleen in optimum number 3-4 days after induction. The suppressor cells affected both the induction and manifestation of DTH. The presence of suppressor and effector cells for DTH inducible by different routes of antigenic presentation reflects the dynamic balance in the regulation of DTH.

Regulation of delayed-type hypersensitivity. I. T suppressor cells for delayed-type hypersensitivity to sheep erythrocytes in mice

An antigen-specific suppressor factor for delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in mice is described. Lymph node cells and spleen cells from mice injected intravenously with 1 x 10(9) SRBC 4 days previously were incubated in vitro for 48 h in culture medium. Supernatant obtained from the culture inhibited the induction of DTH to SRBC in normal mice. It also suppressed the expression of DTH in presensitized mice. The suppression is specific as the suppressor factor had no effect on the DTH to noncross-reacting antigen, chicken red blood cells. Treatment of the spleen cells with anti-theta serum and complement prevented the production of the suppressor factor, whereas treatment with anti-Ig serum and complement had no effect. Suppressor factor produced by H-2k mice suppressed the DTH in H-2b mice. The factor thus seems to act across the H-2 barrier. The suppressor factor was not removed by adsorption with goat anti-mouse immunoglobulin immunoadsorbent, but could be adsorbed by SRBC. It was stable at 56 degrees C for 1 h, but was partially inactivated by freezing and thawing. The factor has a molecular weight of less than 35 000 daltons.

F. Y. Liew

Papers

Regulation of delayed-type hypersensitivity. III. Effect of cyclophosphamide on the suppressor cells for delayed-type hypersensitivity to sheep erythrocytes in mice.

Regulation of delayed-type hypersensitivity. I. T suppressor cells for delayed-type hypersensitivity to sheep erythrocytes in mice

Regulation of delayed-type hypersensitivity. II. Specific suppressor factor for delayed-type hypersensitivity to sheep erythrocytes in mice.