The effect of thymectomy and anti-thymocyte serum on the immunological competence of adult mice

The immune response of normal mice, adult thymectomized mice, micetreated with anti-thymocyte serum and ice which were treated with antithymocyte serum (ATS) after hymectomy were studied for their response to tobacco mosaic virus (TMV) as antigen, 52, 84 and 316 days after the beginning of treatment. Adult mice, treated after thymectomy with ATS, failed to produce detectable antibodies to TMV. The role of the thymus in the adult mouse in the immune response to a thymus-dependent antigen is discussed.     

The appearance of immunological competence at an early age in New Zealand black mice

Adult and 5-day-old New Zealand Black (NZB) and Ju control strain mice were injected with sheep red blood cells. At various times after injection they were killed and the spleens, lymph nodes and thymus tested for haemolysin-producing cells. When the response was expressed as plaque-forming cells (PFC) per million viable cells, the response curve of the spleens of baby NZB mice was very similar to the response in the spleens of the adults, and the response in the lymph nodes of the babies was as high and more sustained than that of the adults. In Ju control strain baby mice of this age, the response in the spleen and the lymph nodes was both reduced and delayed compared with the adults. Neither strain gave a significant response in the thymus. The spleen and lymph nodes of adult NZB mice showed a response which was delayed but not reduced as compared with the adults of the Ju control strain, whereas in baby NZB mice the spleen and lymph nodes showed a response which was advanced and increased (particularly in the lymph nodes) compared with control strain babies (Ju, Swiss, C57B1, CBA). The NZB mice did not reach this level of responsiveness until they were 4–5 days old.     

The role of lymphoid cells in bone resorption: Cellular immunological competence in ia rats

The ia (incisors absent) rat is a naturally occurring mutant that has osteopetrosis resulting from reduced bone resorption. A number of in vestigators have reported that other osteopetrotic mutant rats (op) and mice (mi and op), in addition to demonstrating the skeletal manifestations of the disease, have cellular immunological defects. In light of the fact that bone resorption has been demonstrated to be controlled by hematopoietic tissues and more specifically by mononuclear cells isolated from lymphoid organs, it seemed appropriate to investigate immunological competence in the ia rat, to determine whether or not it had this defect in common with the op rat. Contrary to the results presented for other osteopetrotic mutants, we found that the thymuses in our ia mutants had a normal cellular composition and the T-cell-dependent zones in the lymph nodes were not deficient in lymphocytes. Therefore, this study was undertaken to investigate the response of ia rats to oxazolone, which produces one type of T-cell-dependent immune response, delayed hypersensitivity. The results of these studies indicate that ia rats at 18 days of age have the ability to develop delayed hypersensitivity, as shown by both a blastogenic response in the lymph node draining the site of sensitization and a positive skintest. The magnitudes of these responses were similar in ia and normal littermates, both histologically and quantitatively. Therefore, the ia mutant does not appear to have a defect of the thymus-dependent immune system, and further studies should be carried out to investigate other parameters of immunological competence in these animals.     

Effect on the immunological competence of Physalis pubescens L. in mice

Effect of different parts of the Physalis pubescens L. (Pp) on the immunocompetence were investigated in Kunming mice inbred lines. After 35 consecutive days of feeding, the mice were sacrificed to evaluate the immunologic function through the relative weights of spleen and thymus, the delayed type hypersensitivity (DTH), carbon particle clearance test and serum agglutination test. The results are summarised as follows: the pulp of Pp had statistically significant effect on the mice's non-specific immunity, but not on the weight of the mice's thymus. The Pp's pulp, peel and seeds had significant effect on the mice's cellular immunity, respectively, they had regulating effect on the mice's T-lymphocytes. Any part of Pp didn't have statistically significant effect on the mice's humoral immunity.     

The atopic syndrome: in vitro immunological characteristics of clinically defined subgroups of atopic subjects

Total IgE, selected specific IgE antibody levels, C2 and yeast opsonization were measured in four clinically defined subgroups of atopic patients who had previously been HLA-typed. Each group was characterized by a distinctive mean total IgE level and profile of specific IgE responses. All groups gave comparable levels of IgE antibodies to Timothy grass pollen but in patients initially presenting with infantile eczema and who subsequently developed asthma and/or hay fever, IgE antibodies to bovine milk proteins, egg ovalbumin and cat dander were frequently observed whereas in patients initially presenting with hay fever later in life these antibodies were usually absent. Computer assisted analysis failed to show any association between IgE antibody responses and (a) the HLA phenotypes A1,B8 and A3,B7 (b) C2 levels and (c) the yeast opsonization index.     

Early cellular responses to intradermal injection of Kveim suspension in normal subjects and those with sarcoidosis.

In a detailed controlled study of the cellular response to Kveim suspension in vivo we used immunohistological and histochemical methods to examine cryostat sections of immature Kveim biopsy specimens in subjects with sarcoidosis and normal controls. Changes seen at 48 hours, at which time papular reactions have sometimes been reported, are described. Eight cases of sarcoidosis previously confirmed by a positive Kveim test were studied, in five of whom the test remained positive; plus two subjects with sarcoidosis studied prospectively; and four healthy controls. There were two main features of the 48 hour response: collagen disruption with associated histiocytes, which showed increased acid phosphatase activity; and perivascular infiltrates of lymphocytes and small groups of dendritic cells. The T4:T8 ratios in the infiltrates were similar to those found in the peripheral blood of the subjects, and few lymphocytes showed evidence of activation. T lymphocytes were also seen free in the dermis and migrating to the epidermis. Small juxtacapillary clumps of dendritic cells, identified by NA1/34 (= OKT6; Langerhans' cells) and RFD1 (interdigitating cell) monoclonal antibodies, were found. The Langerhans' cells in the epidermis were, however, normal in number and distribution. These features, which were found in all groups, are not consistent with pre-existing hypersensitivity to Kveim suspension in sarcoidosis. Subsequent differences between sarcoid and normal subjects in the development of granulomas in the Kveim response may therefore relate to the different handling of the foreign material by the cells affected, rather than to differences in the early non-specific recruitment of the cells to the test site.     

The relationship between age-dependent immunological competence of host and tumor growth in the hamster-bovine adenovirus type 3 system.

The relationship of aging to carcinogenesis was immunologically examined in the hamster-bovine adenovirus type 3 system. The age of animals at the time of virus inoculation influenced the tumor growth and latency period, but not the tumor incidence. The immunological competence of hamsters to sheep red blood cells became matured around 4 weeks after birth and was not affected by the infection of bovine adenovirus type 3 (BAV-3). The strength of transplant immunity was dependent on the age of animals at the time of immunization. The growth of progressive type of tumors induced by inoculation with BAV-3 into younger animals was inhibited by the repeated inoculation of excess dose of BAV-3, administration of BCG and transfer of sensitized lymphocytes during the tumor latency. The growth of non-progressive type of tumors induced by inoculation with BAV-3 into adult hamsters was accelerated by administration of antithymocyte serum or thymectomy. The tolerance to tumor specific transplantation antigens did not play a critical role in the present system. The blocking activity to sensitized lymphocytes was demonstrated in the sera taken from hamsters developing a progressive type of tumor even in the early period of carcinogenesis.     

Experimental epithelioid cell granulomas, tubercle formation and immunological competence: an ultrastructural analysis

An ultrastructural study of the cells comprising tubercles in experimental mycobacterial granulomas in rats is presented. Tubercle formation was compared in: (1) primary infections due to BCG at 49 days, (2) reinfection with BCG at 7 days, 8 months after primary infection and (3) lesions due to preformed BCG/anti-BCG complexes in antibody excess in unprimed animals at 10 days. The most rapid elimination of antigen with resolution of the lesion in the reinfection lesions, was effected by the early recruitment of cells morphologically characteristic of activated macrophages and immature epithelioid cells. The next best performance was in the immune complex lesion which at its height was maintained by a roughly constant size due to promonocytes, monocytes, macrophages, activated macrophages and immature epithelioid cells accumulated at the site. True epithelioid cells were rare. The slowest rate of healing in the primary 49 day granulomas, was associated with the whole spectrum of mononuclear phagocyte series of cells. All granulomas were surrounded by a cuff of mixed lymphocytes, interdigitating cells and fibroblasts. The rapid resolution of the reinfection lesions appeared as a loosely compacted infiltration of cells which allowed intimate contact of lymphocytes and macrophages. This was distinct from the tightly compared and compartmentalised zones of lymphocytes and macrophages which inhibited contact in the most slowly resolving lesions. An intermediate arrangement was seen in the immune complex granuloma. Another factor which predisposed to rapid resolution was the high vascularity of the central region of the granulomas. In the slow resolving group vascularity was diminished and peripherally situated.     

Some immunological characteristics of subjects suffering from frequent herpes simplex virus recrudescences

Some parameters of specific and non-specific immunity were tested in a group of 44 subjects suffering from frequent herpes simplex type 1 (HSV-1) or herpes simplex type 2 (HSV-2) recrudescences. The tests performed included determinations of (i) HSV complement-independent and complement-dependent neutralizing antibodies, (ii) antibodies to glycoprotein C of HSV-1 and glycoprotein G of HSV-2, (iii) antibodies to viral capsid and early antigens of Epstein-Barr virus, (iv) antibodies to tetanus toxoid, (v) serum levels of IgM, IgG, IgA, transferrin, prealbumin and C'3 and C'4 components of complement, (vi) active and total T lymphocytes, (vii) phagocyting activity of polymorphonuclear neutrophils, eosinophils and mononuclear cells, (viii) skin reactivity to tuberculin, toxoplasmin, candidin, tetanus and diphtheria toxoids. In the patients the following deviations from the control groups were noted: (i) Antibody levels to homotypic but not to heterotypic HSV were enhanced, (ii) serum IgM levels were elevated, (iii) percentages and numbers of active and total T lymphocytes were decreased, (iv) phagocyting activity of neutrophils was depressed but that of eosinophils was increased.     

Comparison of cutaneous sarcoidosis with systemic sarcoidosis: a retrospective analysis

Objective: To investigate clinical characteristics and treatment effect of sarcoidosis with cutaneous lesions in Chinese patients, and to compare them with previous works. Methods: Retrospective analysis was conducted based on clinical manifestations, systemic examinations and treatment of biopsy-proved 36 patients with sarcoidosis with cutaneous lesions in our hospital since 2000. Patients were divided into cutaneous sarcoidosis (CS) group without systemic involvement and systemic sarcoidosis (SS) group with systemic involvement according to whether extracutaneous systems were involved. Results: Male to female ratio was 1:4.1 in total 36 patients. Average age of onset was (43.6±15.8) years old in CS group and (54.4±11.5) years old in SS group. The most common cutaneous lesions were papulonodules (41.7%) and frequently found in limbs (61.1%). There were 26 patients in SS group, and lung was the most common organ with systemic involvement, followed by lymph nodes. In SS group, elevation of inflammatory parameters and evident changes of chest radiologic examination were often observed. 72.2% patients were treated with glucocorticoid and the overall therapeutic efficacy rate was 48.4%. The therapeutic efficacy in CS group (80%) was significantly higher than SS group (33.3%). Papulonodules type had better response to therapy and usually resolved after treatment. Lupus pernio type was resistant to treatment. Conclusion: Sarcoidosis occurs more frequently in females. Lung is the most commonly affected extracutaneous organ in SS patients. CS patients have better response to therapy than SS patients. Types of cutaneous lesions and existence of systemic involvement are related to prognosis of cutaneous lesions.     

Antibody production in organ culture by bursae of mature chickens and the development of immunological competence

Antibody responsiveness of bursal lymphocytes was studied in vitro. Organ culture of bursal tissue in the presence of antigen, either sheep erythrocytes or bovine serum albumin, results in significant numbers of plaque-forming cells (PFC) compared to controls. The response in organ culture is age-dependent in that only bursae from chickens at least three weeks of age contained significantly increased numbers of secreting cells. Prolonged culture of normally unresponsive bursae from newly hatched birds results in a PFC response to antigen, suggesting that in vitro maturation occurs.     

The immunological synapse

The immunological synapse plays a central role in organising the immune system. Through their synaptic activity both T and B cells usually, but not always, acquire the information that critically determines the level and nature of the responses that they make. For T cells much of that information comes from epicrine and paracrine cell-cell interactions in the cluster that forms around a dendritic cell. These interactions are being dissected by experiments in which two populations of TCR-transgenic T cells are combined in vivo. Another important aspect of synaptic activity is the way in which different levels of expression of MHC class II molecules influence Th1/Th2 balance. In exploring this form of control we are learning something of general importance about cis-regulation.     

The immunological synapse

The induction of a proper adaptive immune response is dependent on the correct transfer of information between antigen-presenting cells (APCs) and antigen-specific T cells. Defects in information transfer may result in the development of diseases, e.g. immunodeficiencies and autoimmunity. A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning IS formation, appearance, and cessation. In addition, proposed functions of the IS are discussed. The process of IS formation occurs in a sequential manner, initially causing a remarkable large-scale redistribution of a number of integral membrane and cytosolic proteins. At the T cell/APC interface the structure comprises in its nascent stage a non-random pattern of protein distribution. The protein pattern is regulated during development of the mature IS and is finally organized into concentric rings of co-receptors and adhesive molecules surrounding the T cell antigen receptor (TCR). The relocations of proteins are influenced by passive as well as active mechanisms. Considering the IS as a device enabling cell-cell communication, clarification of its exact function is of huge general as well as therapeutic interest.     

Simultaneous testing of immunological sensitization to multiple antigens in sarcoidosis reveals an association with inorganic antigens specifically related to a fibrotic phenotype

Organic and inorganic antigens were studied simultaneously in the same cohort of sarcoidosis patients to investigate whether correlations between clinical characteristics and immunological sensitization could reveal new phenotypes. Sensitization to antigens of mycobacteria, Propionibacterium acnes catalase and vimentin was investigated in 201 sarcoidosis and 51 obstructive sleep apnoea patients, serving as control group. Sensitization to aluminium, beryllium, silica and zirconium was also studied in 105 of the sarcoidosis patients and in 24 of the controls. A significantly higher percentage of sarcoidosis patients (27·6%) than controls (4·2%) had an immunological response to metals or silica (P = 0·014). A higher percentage of these sarcoidosis patients showed fibrosis on chest X‐ray 5 years after the diagnosis (69·2 versus 30·3%, P = 0·016). No significant differences in mycobacterial or vimentin enzyme‐linked immunospot (ELISPOT) assay results were observed between sarcoidosis and control patients. A significantly lower percentage of sarcoidosis patients (3·5%) than control patients (15·7%) had a positive ELISPOT for P. acnes catalase (P = 0·003). However, sarcoidosis patients sensitized to P. acnes catalase were more likely to have skin involvement, while sarcoidosis patients sensitized to mycobacterial antigens were more likely to have cardiac involvement. Our study suggests a more prominent role for inorganic triggers in sarcoidosis pathogenesis than previously thought. Immunological sensitization to inorganic antigens was associated with development of fibrotic sarcoidosis. No association was found between sensitization to bacterial antigens or vimentin and sarcoidosis in Dutch patients. However, our data suggest that trigger‐related phenotypes can exist in the heterogeneous population of sarcoidosis patients.     

The -308G/A polymorphism of TNF-alpha influences immunological parameters in old subjects affected by infectious diseases

Abnormal increments of pro-inflammatory cytokines (IL-6 and TNF-alpha) characterize the outbreak of infectious diseases, which are the major cause of death in the elderly. A counterbalance to the inflammation is exerted by IL-10 with an inhibitory role on TNF-alpha production. As is well known, some cytokine gene polymorphisms influence the cytokine production, playing a role as susceptibility or resistance factors against immune-mediated and infectious disease. Genetic variations in the -308A/G locus for TNF-alpha seems to affect the clinical outcome of some infectious diseases. In fact, the -308A allele is associated with severe septic shock and death. On this basis, we have screened healthy old subjects, nonagenarians and old patients affected by the acute phase of chronic obstructive bronchitis and bronchopneumonia of bacteria origin for the -308G/A locus (PCR-RFLP). Subjects are grouped in A+ (AG, AA genotypes) and A- (GG genotype) and data on IL-6, TNF-alpha, IL-10, NK cell cytotoxicity, zinc and metallothioneins (MTs) gene expression (RT-PCR) were stratified according to different TNF-alpha genotypes. The frequency of the A allele was increased in infected patients in comparison with healthy old controls. No differences existed between A+ and A- young adult, old and nonagenarian controls in tested parameters. Conversely, A+-infected patients displayed elevated IL-6, TNF-alpha and MTmRNA, low IL-10 coupled with impaired NK cell cytotoxicity and lower zinc ion than A- patients. However, the data reported are gender independent. Therefore, the -308A polymorphism at the locus of TNF-alpha may be one of the susceptibility factor for infectious diseases in old persons, particularly considering its association to the increased release of pro-inflammatory cytokines and to the reduction of zinc release and MTs synthesis involved in the control of the inflammatory response. These data strongly suggest that the genetic screening of the -308G/A polymorphism may be a valid tool for identification of subjects needing a more appropriate therapy when affected by acute and/or recurrent infectious diseases.