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.     

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.     

Development of the graft versus host reaction and its influence on pregnancy in mice following heparin administration]

The influence of heparin on the graft-versus-host reaction (GVHR) and the peculiarities attending the development of pregnancy in female animals which survived after the GVHR were studied. Preliminary administration of heparin to the recipients prevented their death or increased their life span. An intensification of the GVHR was noted after the administration of heparin to donors or its addition to the transplanted cells. In mice which survived after the GVHR as a result of heparin administration the intrauterine fetuses death and abortions were noted in 60-100% of cases during subsequent pregnancy (3 to 6 months after the cell transplantation). In the case of repeated pregnancies of these female animal pathology of pregnancy was less frequent; however, some of the offspring displayed the rant syndrome. No such disturbances of pregnancy were observed in mice given heparin alone or in those which survived after the transplantation of lymphoid cells only. The sustained pregnancy promoted the intensification of the GVHR induced in the female animals earlier after the heparin administration.     

In vivo differentiated cytokine-producing CD4(+) T cells express functional CCR7

Chemokines and their receptors fulfill specialized roles in inflammation and under homeostatic conditions. CCR7 and its ligands, CCL19 and CCL21, are involved in lymphocyte recirculation through secondary lymphoid organs and additionally navigate lymphocytes into distinct tissue compartments. The role of CCR7 in the migration of polarized T effector/memory cell subsets in vivo is still poorly understood. We therefore analyzed murine and human CD4(+) cytokine-producing cells developed in vivo for their chemotactic reactivity to CCR7 ligands. The responses of cells producing cytokines, such as IFN-gamma, IL-4, and IL-10, as well as of subsets defined by memory or activation markers were comparable to that of naive CD4(+) cells, with slightly lower reactivity in cells expressing IL-10 or CD69. This indicates that CCR7 ligands are able to attract naive as well as the vast majority of activated and effector/memory T cell stages. Chemotactic reactivity of these cells toward CCL21 was absent in CCR7-deficient cells, proving that effector cells do not use alternative receptors for this chemokine. Th1 cells generated from CCR7(-/-) mice failed to enter lymph nodes and Peyer's patches, but did enter a site of inflammation. These findings indicate that CD4(+) cells producing effector cytokines upon stimulation retain the capacity to recirculate through lymphoid tissues via CCR7.     

Th1-biased tertiary lymphoid tissue supported by CXC chemokine ligand 13-producing stromal network in chronic lesions of autoimmune gastritis

Secondary lymphoid tissue is developmentally programmed and characterized by well-ordered compartmentalization of lymphocyte subsets and specialized stromal cells supporting the tissue architecture. By contrast, tertiary lymphoid tissue is defined as that induced in ectopic sites by inflammation, although its immunological role is largely unknown. In this study, we characterize the lymphoid tissue induced in the chronic lesion of murine autoimmune gastritis (AIG). Within the lymphoid cluster in the gastric mucosa, there is a clear segregation of T and B cells. Follicle-like B cell areas are always located on the luminal side of the mucosa, while T cells are located in the basal part. A typical lymphoid reticular network and follicular dendritic cells support the structure. Importantly, complement receptor 1(+) follicular dendritic cells within the follicle express a B cell homing chemokine, CXC chemokine ligand 13. The number and size of the clusters correlate with the age of the mice and the serum autoantibody titer, suggesting the functional importance of the clusters in local Ab production, although involvement of the autoantibody in the disease progression is still unclear. AIG gastric lesions are known to constitute a Th1-biased, memory T cell-dependent immunomicroenvironment. The expression pattern of cytokines, including lymphotoxin-beta, and chemokines in the AIG stomach is consistent with this observation. Taken together, these facts suggest that, during the chronic phase of autoimmunity, long-lasting lymphocyte infiltration probably induces a unique tertiary lymphoid tissue that has a function distinct from that of regional lymph nodes. These neolymphoid tissues may maintain the local self reactivity supporting the vicious cycle of Th1-type reaction as well as autoantibody production.     

White pulp compartments in the spleen of the turtle Mauremys caspica

Summary The aim of the present study was to analyze the nature of lymphoid and non-lymphoid cellular components occurring in distinct histological compartments of the splenic white pulp of the turtle, Mauremys caspica, in order to define their possible correlations with those of the spleen of higher vertebrates, principally mammals. The white pulp of M.caspica consisted of 3 clearly distinguishable regions: (1) the periateriolar lymphoid sheath, and (2) the inner and (3) the outer zones of the periellipsoidal lymphoid sheath. Reticular cells intimately associated with reticular fibres constituted an extensive meshwork in the periarteriolar lymphoid sheath which housed principally Ig-negative lyphoid cells, mature and immature plasma cells, and interdigitating cells. A few Ig-positive cells were also present in the peripheral region of the periarteriolar lymphoid sheath. The inner and outer zones of the periellipsoidal lymphoid sheath were separated by a discontinuous layer of reticular cell processes. In the inner zone, surface Ig-positive lymphoid cells predominated as well as dendritic cells, resembling ultrastructurally the mammalian follicular dendritic cells, although no germinal centres were found in the turtle spleen. Macrophages, some cytoplasmic Ig-positive cells, and Ig-negative lymphoid cells appeared in the outer zone of the periellipsoidal lymphoid sheath. These results allow us to speculate on a phylogenetic relationship between the periarteriolar lymphoid sheath and the inner and the outer zones of the periellipsoidal lymphoid sheath of the spleen of M. caspica and the periarteriolar lymphoid tissue, the lymphoid follicles and the marginal zone, respectively, of the mammalian splenic white pulp.     

The role of M cells in the protection of mucosal membranes

 The mucosa-associated lymphoid tissues continuously take up antigenic matter from the lumen to generate immune responses or to maintain immune tolerance. This antigen sampling is performed by highly specialised epithelial cells, the membranous (M) cells of the dome epithelia. M cells possess a unique ultrastructure and lie in close contact to lymphoid cells. They endocytose soluble and solid substances, including entire microorganisms, at their apical membrane, transport these in vesicles to their basolateral membrane and exocytose them to the intercellular space. This review summarises the structural and functional peculiarities of M cells in different species and at the different sites of lymphoid tissue along the digestive and respiratory tracts. Specialisations of M cells for antigen uptake and transport comprise the composition of their apical membrane and its glycocalyx, a modified cytoskeleton as compared to enterocytes and a pocket-like invagination of the basolateral membrane populated by lymphocytes and macrophages. Besides ultrastructural characteristics, histochemical markers are listed that are currently available for detecting M cells by light microscopy. The origin, differentiation and distribution of M cells and other epithelial cell types of the dome epithelium are outlined. As M cells are used as entry sites by various pathogens and, in the future, might be employed for the oral application of vaccines and drugs, the clinical relevance of M cells in health and disease is discussed. Accepted: 4 August 1997     

Morphologic aspects of cardiac myocyte differentiation in Black Sea--Sea of Azov sturgeon (Acipenser güldenst?dti colchicus V. Marti)]

Processes of ultrastructural organization of cardiac myocytes have been studied in the Russian sturgeon (Acipenser güldenst?dti colchicus V. Marti) during germinal, prelarval, larval periods of development and in mature specimens. One of the main peculiarities of early cardiogenesis in this representative of Chondrostei fishes is a prolonged, observed during germinal and early prelarval periods, repression in multiplication of myocardial cells. Decreasing amount and size of yolk platelets in cytoplasm of these cells at the end of the germinal period could be connected with their intensive specific differentiation and increasing functional activity. Accumulation of free lipids during this period and their decreasing contents in early prelarval period demonstrate a certain transition to another way of metabolism. The data obtained on ultrastructure in mature specimens corresponds mainly to modern ideas on organization of the cardiac muscular tissue in other species of lower vertebrates.     

A comparison of the dynamics of changes in large intestinal mucosa of acute dysentery patients with detection of a specific antigen in urine

The relationship between the elimination of shigellae from the body with urine and the dynamics of morphological changes in the mucous membrane of the large intestine of acute dysentery patients at the early convalescence period has been studied. The persistence of Shigella antigen in acute dysentery patients and its elimination with urine is, as a rule, accompanied by local immune cell reaction in the mucous membrane of the large intestine. The antigen circulating in the body is a factor contributing to the inflammatory process in the intestine, the amount of the eliminated antigen being higher in pronounced inflammations of the intestinal mucosa than in residual inflammatory phenomena. A group of patients (3 persons) releasing Shigella O-antigen with urine and having the inflammatory process in the large intestine, but showing no signs of local immune reaction in the lymphoid tissue of the large intestine, has been found. The reactivity of the lymphoid tissue of the intestine in such patients is a risk factor contributing to the development of prolonged dysentery or chronic postdysenteric colitis.     

Perivascular lymphoid tissue associated with the axillary lymph sinus and the lateral vein of Gehyra variegata (Reptilia:Gekkonidae)

The axillary sinus of G. variegata is formed from a perivascular lymphatic which locally invests the lateral vein. Within the sinus the wall of the vein is distended by lymphoid tissue which is itself supported by reticular fibres. Lymphocytes, reticular cells, macrophages and mast cells occur in the tissue. The overall appearance of the structure is lymph node-like. Although Cardianema sp. (Nematoda:Filarioidea) parasitised the lymphatic system of some geckos examined, the non-pathologic origin of the lymphoid tissue is indicated by its presence in both axillae of infected and uninfected geckos alike. Comparison is made with lymph nodes and node-like structures in other vertebrates.     

Heterogeneous histochemical reaction pattern of the lectin Bandeiraea (Griffonia) simplicifolia with blood vessels of human full-term placenta

Bandeiraea simplicifolia lectin (BS-I) stains vascular endothelium in various species. In humans, less than 10% of the specimens studied exhibit a reaction with BS-I. In the present histochemical study, the reactivity of BS-I with placental blood vessels and its correlation with the blood group from mother and newborn child was investigated. Acetone-fixed cryosections of representative tissue segments of human full-term placenta and umbilical cord were stained with BS-I. The staining pattern of tissues from patients with different blood groups was identical, although the reaction of BS-I in the placenta was heterogeneous. BS-I did not react with the umbilical cord. Vascular smooth muscle cells at the insertion site of the umbilical cord into the chorionic plate, and endothelium deeper in the chorionic plate, became progressively stained. The endothelial cells and tunica muscularis of smaller arteries and veins in stem villi lost their reactivity in parallel with decreasing vessel size. Arterioles and venules reacted heterogeneously. Capillaries, trophoblastic basement membranes, especially epithelial plates, and sometimes the syncytiotrophoblast were labelled in several terminal villi. The data indicate that 1) the placenta binds BS-I to fetal endothelium independent of the blood group, 2) cell-surface antigens on placental endothelial cells are expressed heterogeneously and 3) cell-surface glycans are constituted in an organ-specific manner on human endothelial cells.     

Structural organization of the adrenal cortex in rats with different types of autonomic reactivity under standard conditions and after exposure to different altitudes

The structural organization of adrenal cortex has been studied in intact rats and after short-term hypoxia exposure on different altitudes (2, 6, 8, 11 km). Previously rats have been divided into 3 groups by adrenaline test for determining of vegetative reactivity type. It has been found that some histochemical and morphometric indices of adrenal cortex had peculiarities with respect to type of vegetative reactivity (width of zones, their ratio, nuclear diameter, ascorbic acid content and its distribution and other) in intact rats. Under altitude these differences form individual character of steroidogenesis and determine resistance and reactivity of organism.     

Distribution and morphologic characteristics of lymphoid cells in the canine popliteal lymph nodes in their normal state and under antigen effect

By means of morphometry, light and electron microscopy methods peculiarities in distribution of small, middle and large lymphocytes, as well as plasmocytes in various zones of the popliteal lymph nodes have been studied in normal and in dynamics up to one year after subcutaneous injection of BCG vaccine into the left hind paw. The antigen produces certain changes in density and morphological parameters of lymphoid cells both in the regional and in the contralateral lymph nodes. For them 3 periods are specific. During the first 3 days they are not antigen-dependent (stipulated by the stress reaction), during 7-24 days antigen-dependent processes of proliferation and differentiation of lymphocytes get into action. In 3 months a new wave of the immune response is observed.     

Barrier cells in gills of the alligator gar

Studies of barrier cells in fishes are few and have been restricted primarily to salmonids. Moreover, these studies revealed the presence of barrier cells only in hematopoietic and lymphoid organs. The alligator gar, Lepisosteus spatula, possesses similar tissues within the gills which are readily accessible; therefore, they were the organs of choice. An electron microscopical analysis of the gills was undertaken to determine if barrier cells exist and if they possess an ultrastructural design comparable to their counterparts in the brain and lungs of higher vertebrates and hematopoietic/lymphoid tissues in fishes. The present study revealed that barrier cells were found only within non-hematopoietic/lymphoid areas. Barrier cells surrounded endocrine components, nerves, and sinusoids rather than capillary endothelium or hematopoietic/lymphoid tissues. Barrier cells in the alligator gar displayed a complex envelopment more similar to those found in the blood-cerebrospinal fluid, blood-brain, and blood-gas barriers in higher vertebrates than in salmonids. The barrier in the alligator gar consisted of: (1) an endothelium whose cells displayed tight junctions; (2) a basement membrane; and (3) an outer adventitia composed of fibrocytic cells in syncytium.     

Ultrastructural changes in the spleen of the natterjack,Bufo calamita,after antigenic stimulation

Summary In the present study comparative aspects of the ultrastructure of the spleen were analyzed in non-immunized and T-dependent antigen-challenged natterjacks, Bufo calamita. Special attention is focused on the role of the non-lymphoid components in the splenic immunoreactivity. Ten days after primary immunization with sheep erythrocytes, splenic lymphoid follicles increase considerably in number and size. By that time, lymphoblasts, medium and large lymphocytes abound in the periphery of the white pulp near the marginal zone. Meanwhile, in the red pulp numerous monocytes migrating across the sinusoidal walls apparently transform into giant, dendritic-like cells. Twenty days after immunization the splenic lymphoid follicles decrease in number, although certain reactivity persists and numerous plasma cells occur in the cell cords and sinusoids of the red pulp. These results are discussed comparatively with those reported in other lower vertebrates.     

Cellular composition of tracheal lymphoid tissue in children in their first year of life]

By means of morphometrical methods in histological preparations the quantitative relations of various cell types of lymphoid formations has been studied in newborns and in suckling children. The trachea in the newborns practically does not possess any morphological substrate in the form of lymphoid accumulations, responsible for immune defense of the organ from any external influence. Development of the lymphoid tissue begins in the suckling age and its cytoarchitectonics depends on their localization in the organ's wall. A special place among the accumulations of the lymphoid cells occupy connective tissue spaces of the tracheal glands, where besides lymphocytes and fibroblasts a great amount of plasma cells is situated. Under epithelium these cells are in the least amount, in the prenoduli they are of an intermediate amount. In all the lymphoid structures investigated reproductive function is absent; this is proved by absence of blasts and mitotically dividing cells. Increase in amount of the tracheal lymphoid formations in all age groups studied takes place at the expense of cells migration across blood vessels.     

Syngeneic GvH induced in popliteal lymph nodes by spleen cells of old C57BL/6 mice.

The frequency of autoimmune processes seems to increase with age. We have studied here whether lymphoid cells of aged mice have the potential to express autoreactivity by the use of the in vivo graft-vs-host (GvH) assay. It was found that spleen cells from old (104 weeks) C57BL mice caused significant enlargement of the popliteal lymph node upon injection into the footpads of syngeneic young or old recipients. Histologically this enlargement presented characteristics of a GvH reaction. This effect, which was not abolished by irradiation of the hosts, was totally cancelled by in vitro irradiation or by anti-theta treatment of the donor cells. These results indicate that T cells from aged mice have the potential to manifest autoimmune reactivity.     

Cholinergic and adrenergic innervation of the arteries of the base of the brain in certain lower vertebrates]

The arteries in the encephalon base have been investigated by Koelle's and Falck's methods in Teleostei (Anarhichas lupus, Eleginus navaga, Leuciscus brandti, Pelingas), amphibians (Rana temporaria, Rana semiplicata, Bufo bufo) and in reptiles (Testudo horsfieldi, Trionyx chinensis). Cholin- and adrenergic nerve fibres of the encephalic arteries have been revealed in all the vertebrates studied, but their concentration is far from being equal. In fishes and reptiles neural conductors from scarse plexus with wide loops. Concentration of effector neural fibres only in Bufo bufo exceeds that of fishes. In some cases, the arteries of frogs have equal or less density of cholin- and adrenergic neural conductors as compared with those of Pelingas. Certain individual peculiarities are noted in distribution of the effector neural fibres of the encephalic arteries of the vertebrates. In reptiles, the neural apparatus of the encephalic blood vessels reaches a considerable development; it is definitely differentiated into two plexuses - superficial and deep, having a close interconnection. The development of the effector vascular plexus in vertebrates corresponds to increasing mass of the brain and the vascular diameters. Taking into consideration structural peculiarities of the neural conductors and their concentration, it should be recognized that the role of the neural factor in regulation of the cerebral circulation increases in the following order: fishes - amphibians - reptiles.     

Cell populations in a renal lesion produced by local injection of xenogeneic spleen cells in cyclophosphamide-treated rats.

The frequency and distribution of donor and host lymphoid cells in different stages of a lesion produced by injecting mouse spleen cells beneath the renal capsules of rats treated 24 h previously with cyclophosphamide have been studied by immunofluorescent staining with species-specific anti-lymphocyte sera. Donor cells were predominant in the early stages of the reaction and penetrated the outer part of the renal cortex, but by day 7 when the lesion reached its maximum extent most of the infiltrating cells were of host origin. Donor cells never extended deeply into the kidney and they were not uniformly intermingled with the main mass of host cells but their presence seemed to be necessary for the maintenance of the reaction, since it began to decline when donor cells were no longer detectable in the injected kidney.     

Interactions between endothelial cells and leukocytes

We present evidence that specific receptors are utilized by neutrophils to control their interaction with endothelial cells at sites of acute inflammation and that these receptors are related if not identical to lymphocyte "homing receptors" for lymphoid tissue high endothelium. We speculate that such receptors play a fundamental but not exclusive role in controlling the extravasation and tissue localization of all bone marrow-derived nucleated cells. In addition, we emphasize the active role of endothelial cells in the process of lymphocyte migration and leukocyte extravasation. By the expression of as yet unidentified organ-specific determinants for lymphocyte recognition, endothelial cells control the exit of particular lymphocyte subsets into mucosal versus nonmucosal sites, thus helping to determine the unique features of mucosal versus nonmucosal immune responses. Furthermore, we argue that endothelial cells are exquisitely responsive to local immune reactivity and present evidence that specific lymphokines, including gamma-interferon, play an important role in inducing postcapillary venules to express differentiated features required for the support of lymphocyte traffic into lymphoid organs and into sites of chronic inflammation. Leukocytes, endothelial cells, and probably other tissue cell classes appear to interact at multiple levels by a variety of mechanisms to regulate the local extravasation of immune effector cells.