The immune system and age

Basing on numerous facts, obtained during last years at investigation of the immune system organs, a definite idea has been formed on peculiarities of their structure during certain stages of human ontogenesis. The immune organs appear early in embryogenesis and by birth they have reached their morphological maturation. This is evident as formation of diffuse lymphoid tissue in lymphoid noduli, that can have germinative centers, where young cells of the lymphoid line are formed. The immune system organs develop especially quickly after birth during first years of the postnatal ontogenesis. The peak in development of the organs of immunogenesis, amount and size of the lymphoid noduli occurs during the childhood and adolescent age. Each immune organ has its peculiarities that are determined by their place in the organism, value and intensity of antigenic effect. Beginning from the adolescence and youth amount of the lymphoid tissue and lymphoid noduli in the organs decreases, in their place connective and adipose tissue grows out.     

Man the barrier! Strategic defences in the intestinal mucosa

Immunologists typically study the immune responses induced in the spleen or peripheral lymph nodes after parenteral immunization with antigen and poorly defined experimental adjuvants. However, most antigens enter the body through mucosal surfaces. It is now clear that the microenvironment in these mucosal barriers has a marked influence on the immune response that ultimately ensues. Nowhere is the microenvironment more influential than in the gut-associated lymphoid tissue (GALT). The GALT must constantly distinguish harmless antigens that are present in food or on commensal bacteria from pathogenic assault by microbes. It is perhaps not surprising, then, that the GALT contains more lymphocytes than all of the secondary lymphoid organs combined.     

Efferent neural apparatus of the thymus gland, spleen and lymph nodes and its reaction to electric stimulation of the posterior hypothalamic field

At a histochemical investigation of the rabbit lymphoid organs innervation certain peculiarities on histotopography of adrenergic and acetylcholinesterase (AChE)-containing nervous elements have been established. At a chronic experiment by means of a dosed repeated bilateral electrostimulation of the posterior hypothalamic field in the organs mentioned, inhibition of the functional activity has been noticed. It is most specific not for the AChE-containing structures, but for the adrenergic ones, localized to some extent in the parenchyma, as well as along the course of the blood vessels and their adventitium. The results are discussed in terms of modulatory influence of the posterior hypothalamic field on trophic and functions of the lymphoid tissue. This influence is realized both humoraly and via the nervous pathways (either directly using certain ways and connections, or indirectly by means of neurogenic tonus of the intraorganic blood vessels regulation).     

Intravital microscopy: Imaging host–parasite interactions in lymphoid organs

Intravital microscopy allows imaging of biological phenomena within living animals, including host–parasite interactions. This has advanced our understanding of both, the function of lymphoid organs during parasitic infections, and the effect of parasites on such organs to allow their survival. In parasitic research, recent developments in this technique have been crucial for the direct study of host–parasite interactions within organs at depths, speeds and resolution previously difficult to achieve. Lymphoid organs have gained more attention as we start to understand their function during parasitic infections and the effect of parasites on them. In this review, we summarise technical and biological findings achieved by intravital microscopy with respect to the interaction of various parasites with host lymphoid organs, namely the bone marrow, thymus, lymph nodes, spleen and the mucosa‐associated lymphoid tissue, and present a view into possible future applications.     

Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice

The influence of myelopid (MP) on the protective activity of polycomponent vaccine VP-4 prepared from the antigens of opportunistic bacteria was studied on experimental infections of mice, caused by Klebsiella pneumoniae, Salmonella typhimurium and Staphylococcus aureus. In staphylococcal and Klebsiella infections the joint administration of vaccine VP-4 and MP produced more pronounced protective effect than each of these preparations, introduced alone. The protective action of vaccine VP-4 was specially enforced by MP in cases of local staphylococcal infection. Recommendations on the joint use of two or more immunomodulating agents are possible only on the basis of the experimental substantiation of their effect in definite infections.     

Morphofunctional changes in the lymphoid tissue of the respiratory organs in gamma-globulin administration

By means of macro-microscopic, histologic, radioautographic and immunomorphologic methods, three forms of the lymphoid tissue structural organization have been revealed in the rat respiratory organs: a lymphoid cluster, a lymphoid follicle and a lymphoepithelial nodule. After gamma-globulin is administered intranasally, the ratio of the lymphoid cells in the organs mentioned changes: the number of small lymphocytes decreases, while that of middle, large lymphocytes and blast cells increase. The lymphoid follicles consist of a central and a marginal zones, in the lymphoepithelial nodules the subepithelial and paranodular zones also exist. The gamma-globulin administration stimulates DNA synthesis by the cells of the lymphoid type and their proliferation; that results in increasing number of the antibody-synthesizing cells and is accompanied with an increasing titre of antibodies in washing from the bronchial tree. At a repeated stimulation, the processes are more intensive and develop more quickly.     

The development of the lymphoid organs of flounder, Paralichthys olivaceus, from hatching to 13 months

The growth of the lymphoid organs, such as head kidney, spleen and thymus were studied in flounder, Paralichthys olivaceus Temminck & Schlegel, from hatching to 13 months of age. Except for the thymus, all organs grew as the fish grew. By 2 months of age the lymphoid organs attained their maximum relative weight. The organ weight showed a closer correlation to body weight than they did to age. The total number of leucocytes in the lymphoid organs increased with age, but the number per milligram of lymphoid organ remained constant. A micro and ultrastructural study of the lymphoid organs showed that the full development of the lymphoid organs was not achieved until the juvenile stage. The spleen and head kidney had mixed populations of "red" and "white" cells. The head kidney was more lymphoid than the spleen. The thymus involuted quickly during the first 6 months. The blood components had no obvious relationship with age or season during the period studied.     

Local characteristics and interrelations between glands and lymphoid conglomerations in the esophageal wall

Proper glands in 248 total preparations and lymphoid accumulations in 112 preparations have been investigated macro-microscopically in the human oesophageal preparations at various age. The organs have been obtained from 152 corpses of persons died from the death by violence and having no pathological changes in the organs of digestive and immune systems. The lymphoid tissue in the oesophageal wall is presented as accumulations of cells (prenodules++) and as diffusely scattered immune-competent cells. The glands and lymphoid accumulations are oriented as longitudinal rows. The lymphoid tissue accumulations are situated near to the glandular ducts, because the latter can serve as pathways for penetrating antigenic material into the organ's wall. The amount of the glands is maximal mature and elderly age, and that of lymphoid accumulations--at the second childhood. The dimensions of the gland body increase in the cranio-caudal direction, while the lymphoid accumulations, just the reverse, have their maximal dimensions in the upper third of the oesophagus. The gland bodies in places of the organ's anatomical narrowings in the section have more alveoles and are situated nearer to the covering epithelium than the glands in the neighbouring areas of the wall.     

Immunologic 'ignorance' of vascularized organ transplants in the absence of secondary lymphoid tissue

Secondary lymphoid organs (the spleen, lymph nodes and mucosal lymphoid tissues) provide the proper environment for antigen-presenting cells to interact with and activate naive T and B lymphocytes. Although it is generally accepted that secondary lymphoid organs are essential for initiating immune responses to microbial antigens and to skin allografts, the prevailing view has been that the immune response to primarily vascularized organ transplants such as hearts and kidneys does not require the presence of secondary lymphoid tissue. The assumption has been that the immune response to such organs is initiated in the graft itself when recipient lymphocytes encounter foreign histocompatibility antigens presented by the graft's endothelial cells. In contrast to this view, we show here that cardiac allografts are accepted indefinitely in recipient mice that lack secondary lymphoid tissue, indicating that the alloimmune response to a vascularized organ transplant cannot be initiated in the graft itself. Moreover, we demonstrate that the permanent acceptance of these grafts is not due to tolerance but is because of immunologic 'ignorance'.     

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared.     

Plasmacytoid dendritic cells of different origins have distinct characteristics and function: studies of lymphoid progenitors versus myeloid progenitors

Plasmacytoid dendritic cells (pDCs) play a central role in host innate and adaptive immunity and are thought to be of lymphoid origin. However, in IL-7Ralpha-/- mice, which are deficient in T and B lymphocytes, pDCs are still found in lymphoid organs, which suggests that there is a lymphoid-independent pathway for the development of pDCs. Previous work has demonstrated that pDCs originate from both lymphoid and myeloid progenitors (MPs). However, it is not clear whether the function of pDCs is different relative to their origin. In an effort to compare the characteristics and functions between pDCs generated from different progenitors, we performed adoptive transfer studies using highly enriched populations of common lymphoid progenitors (CLPs) and MPs from the bone marrow of control mice and examined their potential and developmental kinetics for the generation of pDCs. Interestingly, although CLPs were polarized to generate pDCs, MPs were polarized to generate conventional dendritic cells and the kinetics of pDC generation from MPs was reached earlier than from CLPs. Furthermore, CLPs have the potential to generate more pDCs on a per cell basis. Moreover, MP-derived pDCs produce relatively higher levels of IFN-alpha than CLP-derived pDCs following CpG stimulation. These data indicate that MPs are multipotential and have the capacity to develop into not only myeloid cells, but also pDCs, which have distinct characteristics and function compared to that of lymphoid origin and, therefore, imply a more important role for MP-derived pDCs in conditions where the function of lymphoid progenitors is impaired or compromised.     

Recovery of the cellular immunity system after sublethal radiation

Dynamics and recovery of quantitative and qualitative characteristics of lymphoid tissue were studied after sublethal irradiation. The data obtained are indicative of a different dynamics of recovery of cells in central and peripheral lymphoid organs, GFUs and antibody-forming elements. The peculiarities have been revealed in a change of functional capacity of some T-lymphocyte populations.     

Effect of cyclosporine on the lymphoid organs of CBA mice]

The influence of cyclosporine which is an immunodepressant on morphology of the lymphoid organs was studied on CBA mice. The immunodepressant was administered intramuscularly in a single LD50 and in a dose of 7 mg/kg for the treatment course of 21 days. The examinations were performed in various periods within 28 days after discontinuation of the drug use. It was shown that cyclosporine induced cell depletion in the thymus cortical and medullar zones, inhibition of lymphocyte mitotic activity, alteration of the Hassall corpuscles and impairment of their formation. It also induced devastation of the thymus-dependent zones in the mesenteric lymph nodes and spleen. When cyclosporine was used in the course doses the morphological changes in all the lymphoid organs were more marked. The morphological changes were reversible.     

Lymphoid neogenesis in chronic inflammatory diseases

The frequent observation of organized lymphoid structures that resemble secondary lymphoid organs in tissues that are targeted by chronic inflammatory processes, such as autoimmunity and infection, has indicated that lymphoid neogenesis might have a role in maintaining immune responses against persistent antigens. In this Review, we discuss recent progress in several aspects of lymphoid neogenesis, focusing on the similarities with lymphoid tissue development, the mechanisms of induction, functional competence and pathophysiological significance. As more information on these issues becomes available, a better understanding of the role of lymphoid neogenesis in promoting chronic inflammation might eventually lead to new strategies to target immunopathological processes.     

Quantitative study of regression and regeneration of the thymic cell population after X-irradiation in the newtPleurodeles waltlii Michah

Summary The changes in cell numbers of different thymic cell populations and the conditions governing the regeneration of these populations and the thymus itself were examined after X-irradiation (700 rads) of different parts of the body. The general effects of the irradiation were studied in each experimental group in terms of mortality and growth rate. The particular effects on each thymic cell population were studied by the measurement of mitotic activity and of evaluation of the changes in numbers among these populations in the thymus itself, and were compared with the effects in the granulopoietic layer of the liver and in the spleen. The great reduction in the number of lymphocytes after irradiation demonstrates that they are more radiosensitive than other cell types; this reduction can be compensated for by the arrival of new lymphoid cells originating from other lymphoid organs (if they have been protected from irradiation) and by allowing thymic regeneration. Thus, irradiation has indirect effects on non-irradiated areas, and demonstrates that the lymphoid cell population has a high potential for multidirectional migration.     

Extrathymic rearrangement of αβT-lymphocyte antigen receptor genes during pregnancy

The existence of alphabetaT-lymphocyte differentiation processes have been demonstrated in mouse peripheral lymphoid organs during pregnancy. Study of pregnant Swiss mice has shown that the development of the second half of gestation is accompanied by expression of RAG-1 recombinase mRNA and unrearranged TCR alpha-chain (pre-TCRalpha) preferentially in T-lymphocytes of lymph nodes involved in uterine drainage (para-aortal lymph nodes), and to a lesser extent in other lymph nodes (mainly from axillary lymph nodes). The data suggest that during pregnancy the differentiation of alphabetaT lymphocytes may occur not only in central (thymus) but also in peripheral lymphoid organs.     

The influence of pineal peptides on in vitro immunoglobulin secretion by Peyer's patches in rats

The influence of the pineal peptides (1 mcg/ml) on immunoglobulin secretion by rat's Peyer's patches isolated from nonimmunized rats and from orally immunized by ovalbumin during 40 min incubation, was investigated. Using alpha- and beta-adrenoblockers--phentolamine hydrochloride (0.02 mg/ml) and anaprilin (0.6 mg/ml), respectively--the possibility of pineal peptides' effect on the gut secondary lymphoid organ' adrenoreceptors, was evaluated. Basic levels of immunized rats' control Peyer's patches secretory activity were 2.4--fold (p < 0.01) higher than those of non-immunized rats. The effect of pineal peptides on antibody-producing cells' secretory activity depended on Peyer's patches' functional condition. Application of pineal peptides led to a 35% (p < 0.05) increasing of immunoglobulin secretion by non-immunized rat Peyer's patches and to a 25% (p < 0.05) decreasing of antibody production by immunized rats lymphoid organs. These data suggest that the pineal peptides activation influence on Peyer's patches antibody-producing cells of nonimmunized rats connected with alpha-adrenoreceptors, and inhibiting action of these peptides on immunized rats lymphoid organs immunoglobulin secretion are not mediated through adrenoreceptors.     

The morphological characteristics of globulin production during the vaccinal process induced by tularemia and brucellosis vaccines

Significant data on the dynamics of globulin production in guinea pigs in the process of immunogenesis after the injection of Francisella tularensis vaccine strain or conjugated brucellosis vaccine have been obtained by means of immunofluorescence and the enzyme immunoassay. The number of globulin-producing cells in lymphoid organs (the spleen, regional and remote lymph nodes) differs, depending on the injected antigen. The relationship between the character of immunomorphological changes in lymphoid organs and the dynamics of the increase of antibody titers in the peripheral blood of the animals after their immunization with conjugated brucellosis vaccine and the injection of avirulent F. tularensis has been established.