Changes In Humoral Immunity Research Articles

An Alteration of Lymphocytes Subpopulations and Immunoglobulins Levels in Patients with Diabetic Foot Ulcers Infected Particularly by Resistant Pathogens.

The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs) especially those infected by resistant microorganisms. Methods. 68 patients treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n = 50) and subgroup R by resistant pathogens (n = 18). Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p < 0.01) and total numbers of lymphocytes (p < 0.001) involving B lymphocytes (p < 0.01), CD4+ (p < 0.01), and CD8+ T cells (p < 0.01) and their naive and memory effector cells. Higher levels of IgG (p < 0.05) including IgG1 (p < 0.001) and IgG3 (p < 0.05) were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p < 0.05). A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS). Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p < 0.01) in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls.

Changes in Humoral Immunity in Children Suffering from Chronic Tonsillitis before and after Tonsillectomy

Changes in Humoral Immunity in Children Suffering from Chronic Tonsillitis before and after Tonsillectomy

The systemic immunity humoral link status in patients with traumatic illness

The influence of trauma on parameters of humoral immunity changes has been studied. The study includes 52 patients with various forms of traumatic illness, aged 18-69 years (37,91±4,28). The control group consisted of 16 patients who had undergone a routine surgery not related to the pathology of musculoskeletal system. All patients of the main group were divided into 3 groups according to the severity of their condition. Analysis of parameters of cellular link of immune system was performed by defining the pool of B-lymphocytes (CD22+ lymphocytes), determination of main classes' immunoglobulins, and calculation of integrated indicators. The highest expression (immune disorders of II-III grades) of changes of cellular immunity was observed in patients with severe traumatic illness (detailed clinical picture). Surgical intervention, even without traumatic injury significantly affect cellular immunity, but in patients with traumatic illness immunity disorders were significantly higher than in the comparison groups.

Food allergy and the oral immunotherapy approach.

Food allergy represents an increasing health problem, with children being the most affected population. The symptoms can appear within minutes or hours of ingesting the offending food, producing skin manifestations, respiratory, gastrointestinal and anaphylactic reactions in the severe forms. Food allergy is established by the loss of tolerance to food proteins, and is characterized by an altered balance of regulatory T (Treg) cells and the shift to Th2 type cytokines in the intestinal lamina propria. We have described the contribution of different factors in establishing oral tolerance, such as the antigenic exposition route, the gut microenvironment, and the timing of the food introduction. Apart from avoiding the food, immunotherapy is the only intervention which produces oral desensitization to food proteins. Among the underlying immunological mechanisms of oral immunotherapy (OIT) are the changes in humoral immunity (a decrease of allergen-specific IgE and an increase of allergen-specific IgG4) and cellular changes such as the increased number of FoxP3(+) Treg cells. At present, the experiences of OIT with various foods are offering promising results. OIT appears to be safe producing low adverse reactions, and effective in inducing desensitization in most subjects with food allergy.

Changes in humoral immunity in sensitized guinea pigs exposed to trichloroethylene

To study the changes of serum complement C and immunoglobulin (Ig) in sensitized guinea pigs exposed to trichloroethylene. Thirty six white female guinea pigs (250 ∼ 300 g) were randomly divided into blank control group (5 guinea pig), solvent (olive oil) control group (5 guinea pig) and TCE treatment group (26 guinea pig). According to guinea pig maximization test (GPMT), guinea pigs were exposed to TCE. After stimulating contact for 24 h, the skin reactions of guinea pig back test area were recorded and scored. According to Skin sensitization integral, the guinea pigs treated with TCE were divided into the sensitized group (score ≥ 1) and un-sensitized group (score 0). The concentrations of serum C3, C4, IgA, IgG and IgM were detected in 24 and 72 h, respectively after the experiment. The sensitization rates of group treated by TCE was 65.38%. The serum C3 levels of groups sensitized to TCE for 24 and 73h were 99.75 ± 1.45 and 93.28 ± 3.61g/ml, respectively, which were significantly lower than that (112.30 ± 9.10 g/ml) of solvent control group (P < 0.05). Also The serum C4 levels of groups sensitized to TCE for 24 and 73 h were 34.63 ± 2.53 and 33.82 ± 2.76g/ml, respectively, which were significantly lower than that (43.87 ± 3.65 g/ml) of solvent control group (P < 0.05). The serum IgA and IgM levels of groups sensitized to TCE and unsensitized to TCE for 24 and 72 h were significantly lower than those of solvent group (P < 0.05). as compared with unsensitized groups, the serum IgA levels of the groups sensitized to TCE for 24 and 72 h significantly decreased (P < 0.05). After the guinea pig skin was sensitized to TCE, the serum C3, C4 levels decreased, the immune function disordered.

Tyrosine Kinase Inhibitor Therapy Induced Changes in Humoral Immunity in Patients with Chronic Myeloid Leukemia

Abstract 1699 Background:By affecting not only BCR-ABL1 but also a wide variety of other tyrosine kinases, tyrosine kinase inhibitors (TKIs) have potential impact on the immune defense system. As patients could use TKIs even for decades, immunological off-target effects may be of significance in clinical practice. The aim of this project was to study the effects of TKI therapy on B-cell-mediated immunity in vivo in CML patients. PATIENTS AND METHODS:Peripheral blood (PB) and bone marrow (BM) samples were collected from newly diagnosed chronic phase CML patients and follow-up samples were obtained during TKI therapy at 1, 3, 6, and 12 months after therapy start (imatinib n=21, dasatinib n=15 and nilotinib n=7). Samples from healthy volunteers served as controls (n=10). Plasma immunoglobulin (Ig) levels were measured with an immunoturbidometric method and BM and PB lymphocyte subclasses were analyzed with multicolor flow cytometry. Ig heavy chain rearrangement PCR according to BIOMED-2 protocol was used to identify clonal B-cell populations among sorted CD19pos B lymphocytes. RESULTS:At diagnosis, before TKI therapy, plasma Ig levels were similar to healthy controls. During imatinib treatment IgA and IgG levels decreased continuously and were significantly lower at 12 months compared either to diagnostic samples or to healthy controls: median IgA level at 12 months 1.22 vs. 1.51 g/l at diagnosis (p=0.040) or vs. 1.61 g/L in healthy controls (p=0.023); median IgG at 12 months 7.00 vs. 8.80 g/l at diagnosis (p=0.009) or vs. 8.55 g/l in healthy controls (p=0.009). Similarly plasma IgM levels decreased: 0.59 g/ at 12 months vs. 1.06 g/l at diagnosis (p=0.0002), but did not differ significantly from healthy controls (0.75 g/l, p=0.331). Positive correlation was found between plasma IgG and IgM levels at 3 months (r=0.678, p=0.045). One imatinib patient developed severe constant hypogammaglobulinemia, which was first noticed at 3 months, and imatinib was discontinued at 15 months due to recurrent respiratory infections.In dasatinib-treated patients, only plasma IgM levels decreased notably, and at 12 months, they were significantly lower (0.39 g/l) compared to diagnosis (0.86 g/l, p=0.011) or healthy controls (0.75 g/l, p=0.037).No statistically significant changes were observed in nilotinib-treated patients, possibly due to small number of patients.The CD45 expression analyzed by flow cytometry was used to detect different B-cell subclasses (CD45high as mature B-cells, CD45intermediate as maturating B-cells and CD45low as immature B-cells). In imatinib treated patients the proportion of mature B-cells in BM from all CD19+ cells was significantly lower at 3 months than in dasatinib group (55% vs. 84%, p<0.05), whereas the proportion of maturating B-cells was higher (34% vs. 12%, p<0.05). This could be related to the observed low plasma Ig levels in imatinib patients, as only mature B-cells are capable of secreting immunoglobulins. BM B-cell profile of nilotinib patients resembled that of imatinib patients.Although clonal T-cells are found in the majority of CML patients (Kreutzman et al. Blood 2010), Ig heavy chain rearrangement analysis did not reveal any clonal B-cell populations in CML patients at diagnosis (n=2) or during imatinib (n=2) or dasatinib (n=9) treatment. Similarly, no marked abnormalities were observed in serum electrophoresis or immunofixation analysis. CONCLUSIONS:Imatinib-treated patients have reduced plasma Ig levels and the proportion of mature immunoglobulin-secreting B-cells was lower in BM. Unexpectedly, dasatinib-induced changes were much less prominent, although dasatinib inhibits a broader spectrum of kinases, some of which are clearly involved in B lymphocyte biology, such as the Lyn-kinase. Further studies are needed to understand which kinase inhibition plays the major role in imatinib-induced reduction of Ig levels. However, the measurement of plasma Ig levels is warranted in patients with recurrent respiratory infections and possibility of hypogammaglobulinemia needs to be taken into account. Disclosures:Koskela:Novartis: Honoraria. Richter:Bristol-Myers Squibb: Honoraria; Novartis: Honoraria. Hjorth-Hansen:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria. Porkka:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria. Mustjoki:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria.

Aging Affects Human B Cell Responses

Aging represents a complex remodeling in which both innate and adaptive immunities deteriorate. Age-related changes in humoral immunity are responsible for the reduced vaccine responses observed in elderly individuals. Although T cell alterations play a significant role in age-related humoral immune changes, alterations in B cells also occur. We here provide an overview of age-related changes in B cell markers and functions. Our studies have shown that intrinsic changes in B cells with age contribute to reduced antibody responses such as those to the influenza vaccine.

Long-term effects on humoral immunity among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

ObjectivesEpidemiological studies have shown inconsistent effects on immunological parameters in subjects exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study we investigated changes in humoral immunity and prevalence of atopic diseases among...

Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population.

The study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particular, a statistically significant age-related increase of the serum level of immunoglobulin classes (IgG and IgA but not IgM) and IgG subclasses (IgG1, 2 and 3, but not IgG4) was detected. A parallel age-related decrease of circulating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age-related modifications of the immune system.

Preferential depletion of a splenic marginal zone-like peripheral blood CD27+B220- memory B cell population in HIV-1 infected individuals

In addition to CD4+ T cell depletion, HIV-1 infection is characterized by changes in humoral immunity including hypergammaglobulinemia, polyclonal B cell activation and loss of circulating memory B lymphocytes. Expression of the CD45 isoform B220 has recently been described on CD27- and a subset of CD27+ human B lymphocytes. The aim of this study was to evaluate B cell defects in HIV infection in more detail. We studied the frequency of memory B cells, based on the expression of B220, in HIV infected individuals (n = 27) and healthy controls (n = 22) and characterized their functional properties. RNA expression of TLR9 and activation-induced cytidine deaminase (AICD) was analyzed by Real-time PCR from B cells sorted according to their memory phenotype. In addition, B-cell proliferative responses and immunoglobulin secretion in response to SAC and ODN treatment were monitored. We found that the previously described reduction in the frequency of CD27+ B cells in HIV-infected individuals affects preferentially the subset characterized by the lack of B220 expression. The proportion of CD27+B220- B cells expressing surface IgD (28.8%) and IgM (29.5%) was reduced in the HIV+ group compared to healthy controls (53.9% and 59.8%, respectively). This depletion did not correlate with either CD4 counts or viral load, and was not reversed by antiretroviral therapy. We found that CD27+B220- B cells have a splenic marginal zone like immunophenotype (IgMhiIgDloCD21+CD23-), express TLR9, and proliferate and secrete IgG and IgM in response to B cell specific ODN. In contrast, CD27+B220+ B cells are IgMloIgDhiCD21+CD23+, express AICD and proliferate in response to SAC but do not secrete immunoglobulins. The lack of B220 expression on CD27+ B cells defines a distinct memory B cell compartment that is preferentially depleted in HIV-infected individuals. The phenotype, pattern of gene expression and functional properties of the preferentially depleted CD27+B220- B cells suggest that these cells are splenic marginal zone-like circulating memory B cells. The lack of these cells in HIV patients may play an important role in the defective immunity against T-independent pathogens and may impair the humoral control of HIV-1 propagation.

Pair housing affects anxiety-like behaviors induced by a social but not by a physiological stressor in male Swiss mice

The role of pair housing in the modulation of anxiety-like behaviour in socially and physiologically stressed mice was investigated. The protocol of psychosocial stress consisted of submitting male adult mice to daily social confrontation with a male conspecific for a period of thirteen days. In an attempt to study a possible effect of pair housing as a social support, each male mouse was housed with a female throughout the period of experimentation, except during the agonistic interactions. As a physiological stressor, 10 9 sheep red blood cells (SRBC)/ml were injected intraperitoneally on the 1st and 7th days of the experiments. The respective control groups were as follows: non-socially stressed, non-pair housed and saline-injected mice. The humoral immune response was analysed by haemagglutination assay. The level of anxiety-like behaviours was measured in the elevated plus-maze test on the 13th day of the experiment. As a result, no significant changes in humoral immunity to SRBC were observed in mice subjected to social confrontation in a neutral arena as compared to non-socially stressed mice. As a consequence, no effect of pair housing on humoral immunity to SRBC could be evaluated. Concerning the effects of pair housing on the anxiety-like behaviours, it was possible to demonstrate that the pair housing proved to be effective in modulating anxiety-like behaviour, although in the stressed groups the percentage of time in the open arms and the time in risk assessment did not change in a symmetrical opposite form, as expected. The physiological stressor induced an anxiety-like behaviour that was not reversed by the pair housed condition. This suggests that different types of stressors activate different neural and peripheral pathways, which may or may not be modulated by pair housing, a finding that deserves our attention as a way to better understand the mechanisms that influence adaptations to stress.

Effect of Age on the Immunoglobulin Class Switch

Aging represents a complex remodelling in which both specific and innate immunity deteriorate. Age-related changes in humoral immunity involve reduced vaccine responses and increased production of auto-antibodies. Although T-cell alterations play a significant role in age-related humoral immune changes, alterations in B cells also occur. In this review, we provide an overview of age-related changes in B-cell functions and markers, including transcription factors, and also discuss controversies in the field of B-cell aging. We summarize our recent results, showing that splenic B cells from senescent mice are deficient in production of secondary isotypes (IgG1, IgG2a, IgG3, IgE), class switch recombination (CSR), and expression of the transcription factor E47. We also demonstrate that there is more Id2 (a negative regulator of E47) in old activated B cells. E47 is required for CSR, at least in part, via expression of activation-induced cytidine deaminase (AID). Our studies show that impaired induction of E47, and, subsequently, AID, contribute to poor CSR and production of secondary isotypes in senescence. We also present new data indicating the absence of DNA switch region excision circles for CSR in old activated B cells, confirming the location of the defect at the DNA endonucleolytic step. And, finally, we show that there is no change in NF-kappaB or Blimp-1 in old vs young stimulated B cells.

Environmental pollution, immunology researches, humoral immunity, immunological indices of risk, pregnant women, new-born, children of the first year of age

Pregnant women in last trimester of pregnancy living in 2 districts of Moscow were clinically examined. The immunology researches show that 69 % of all pregnant have the changes in humoral immunity: decrease of IgG, increase of IgM,CIC,and IgE.&#x0D; It was also found that somatic health of women pregnancy complications and corresponding immunological changes found in last trimester of pregnancy negatively influenced on health of new-born and formation of health during first year of age. So diagnosis of intrauterine fetus hypoxia. Low Apgar score (6 points and lower), brain circulation disorders of hypoxia genesis diagnosis of hypertensional syndrome was significantly more frequent between new-born of ecologically polluted district.&#x0D; The study conducted permitted to substantiate the immunological indices of risk for reproductive health of women and health of their offspring. These are: a) decrease of IgG concentration in blood, b) increase of CIC along with rise of overall IgE, c) presence of antihapten antibodies to environmental pollutants. These indices are recommended for inclusion in social and hygienic monitoring, ordinances of Health Ministry in the sphere of maternity and childhood protection.

Splenic Denervation Blocks Leptin-Induced Enhancement of Humoral Immunity in Siberian Hamsters (Phodopus sungorus)

Nontropical rodents have evolved adaptations to maximize winter survival, including alterations in reproduction, energy balance and immunity. Short-day-housed Siberian hamsters display reductions in body fat and decreases in humoral immunity compared with long-day hamsters. The hormone leptin, secreted by adipose tissue, varies in response to changes in body fat and has been implicated in photoperiodic changes in immunity. In addition, the metabolic effects of this hormone appear to be mediated by the sympathetic nervous system (SNS). Very little is known, however, regarding the role of the SNS in regulating the effects of leptin on immunity. The goal of the present study was to examine the effects of splenic denervation on leptin-induced immune enhancement of short-day Siberian hamsters. Male hamsters were housed in long (LD 16:8) or short days (LD 8:16) for 10 weeks. Half of the animals in each photoperiod received surgical denervations of the spleen; the remaining animals received sham operations. In addition, animals in each group were implanted with osmotic minipumps containing either leptin or vehicle. Hamsters were then injected with keyhole limpet hemocyanin (KLH) and serum anti-KLH antibody production was assessed. Short-day hamsters displayed decreased humoral immunity in short versus long days; leptin attenuated the short-day decrease but did not enhance immunity of long-day hamsters. Furthermore, splenic denervation blocked the leptin-induced increase in immunity in short-day hamsters. Collectively, these data suggest that leptin plays an important role in regulating seasonal changes in humoral immunity of Siberian hamsters and the effects of leptin occur, at least in part, via changes in the SNS innervation of lymphoid tissue.

Exposure to short days, but not short‐term melatonin, enhances humoral immunity of male Syrian hamsters (Mesocricetus auratus)

Many non-tropical rodent species rely on photoperiod as the primary cue to co-ordinate seasonally appropriate changes in physiology and behavior. Among these seasonal changes, several rodent species (e.g. deer mice, prairie voles, Siberian hamsters) adjust immune function in response to changes in ambient day lengths. The goals of the present study were to examine the effects of photoperiod on immune function of Syrian hamsters (Mesocricetus auratus), and to determine the role of melatonin in mediating photoperiodic changes in immunity. In Experiment 1, male Syrian hamsters were housed in long (LD 14:10) or short days (LD 10:14) for 10 wk. In Experiment 2, hamsters were housed in long days and half of the animals were given 10 consecutive days of i.p. melatonin injections (15 microg) in the early evening, while the remaining animals received injections of the vehicle alone. After the respective experimental manipulations, animals were injected with the antigen, keyhole limpet hemocyanin (KLH), blood samples were obtained and anti-KLH IgG antibody production was assessed. In Experiment 1, short-day hamsters underwent gonadal regression and reduced serum testosterone as well as displayed increased humoral immune function compared with long-day animals. In Experiment 2, short-term melatonin treatment did not affect gonadal mass, testosterone or humoral immune function. These results confirm previous findings of photoperiodic changes in immunity in rodents and suggest that changes in humoral immunity are not due to short-term changes in melatonin.

Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention.

Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting beta-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.

Antibody Responses to Sheep Red Blood Cell and Brucella Abortus Antigens in a Turkey Line Selected for Increased Body Weight and Its Randombred Control

Turkeys from a randombred control line (RBC2) and its subline (F) selected for increased 16-wk BW were tested for primary and secondary antibody responses to SRBC antigen and Brucella abortus antigen (BA). Previous studies have shown that the F line was more susceptible to Pasteurella multocida and Newcastle disease virus than was the RBC2 line. Individuals from the RBC2 and F lines were intravenously injected with 1 mL 5% SRBC antigen or 0.1 mL undiluted BA at 4 and 6 wk of age; blood samples were collected at 0, 4, 7, and 10 d post-immunization. Total, IgG, and IgM titers were measured by agglutination assays.Compared with the RBC2 line, the F line had generally higher total anti-SRBC titers; the differences were significant at 14 d postprimary immunization (PPI) (females); at 10 d postsecondary immunization (PSI) (males); and 4, 7, and 10 d PSI (females) (P ≤ or = 0.05). The F line also had higher IgM titers at 14 d PPI (females) and at 10 d PSI (males) (P ≤ or = 0.05). For IgG titers, a line difference was evident in females at 4 and 10 d PSI (P ≤ or = 0.05); the F line had higher titers than did the RBC2 line. For the antibody response to BA in males, the F line had lower total and IgM titers at 10 d PPI (P ≤ 0.05) than did the RBC2 line. No significant line differences in response to the BA were found in total and IgM titers in female turkeys or in IgG titers in both sexes at any time. These results suggest that selection for fast growth rate of turkeys might have resulted in changes in humoral immunity to the SRBC antigen and BA.

Humoral intestinal immunity in systemic lupus erythematosus.

Forty-five patients with systemic lupus erythematosus (SLE) underwent a cross-sectional study to evaluate intestinal secretory immunity. Peroral jejunal biopsy with histologic and immunohistochemical assessment of the mucosa were carried out in the patients and in 12 healthy volunteers. It was observed that an altered pattern of immunoglobulin-bearing plasma cells distributed in the lamina propria and complementary components were invariably present, mainly in the patients with active disease. The basement membrane of the intestinal crypt epithelium exhibited immunoglobulin and complementary deposits, similar to the lupus band test. None of the immunologic findings correlated with the medical treatment and with the peripheral blood analysis. The local changes in humoral immunity in patients with SLE did not correlate with gastrointestinal symptoms and may reflect the systemic effects of the disease.

Effect of age on humoral immunity, selection of the B-cell repertoire and B-cell development.

The age-associated changes in humoral immunity affect the quality more than the quantity of the antibody response. Changes in the quality of the antibody response with age include shifts in antibody specificities from foreign to autoantigens, in antibody isotypes from IgG to IgM, in antibody affinities from high to low and in the antibody idiotypic repertoire. These changes can be traced to an impaired capacity of T cells to facilitate: (a) the maturation of B cells with respect to isotype and affinity maturation in the periphery and (b) the development of a diverse B-cell repertoire from precursors within the bone marrow. In contrast, there is no evidence that the amount of immunoglobulin produced before or after immunization diminishes with age. Nonetheless, the impaired responses of the elderly to most vaccines and the greater susceptibility of the elderly to infections has fostered a view that immune senescence leads to a state of immune deficiency. However, it is more precise to describe immune senescence as leading to a state of immune dysregulation. The dysregulation of the humoral immunity is manifested by a shift from adaptive humoral immunity, characterized by the production of a highly specific, high-affinity, IgG antibody response to foreign antigens, to a process of natural antibody-mediated immunity, dominated by low-affinity, polyreactive, IgM antibodies which react with autoantigens. Age-associated T-cell impairments appear to be the basis for the shift from adaptive to natural humoral immunity and their reversal should permit the restoration of an adaptive antibody response in the elderly.

Additive effect of diabetes and systemic hypertension on the immune mechanisms of atherosclerosis

In order to evaluate the changes in humoral immunity due to one and two atherogenic factors (systemic hypertension and/or diabetes mellitus), we investigated 350 women divided into four groups: (1) 65 insulin-dependent (type I) non-hypertensive diabetics; (2) 92 systemic hypertensive non-diabetic subjects; (3) 64 hypertensive insulin-dependent diabetics; and (4) 129 non-hypertensive and non-diabetic women as a control group. All subjects had no coronary artery disease. The humoral immunity was evaluated by (1) circulating immune complexes, (2) total serum complement, (3) C3 fraction of complement, and (4) circulating antitissue antibodies (antivascular and antisclerotic-vascular). The patients with atherosclerotic risk factors (diabetes and/or hypertension) had significantly ( P < 0.001) elevated levels of total complement, C3 fraction and circulating complexes compared with the control group. Total complement and circulating complexes levels were most elevated in patients with a combination of diabetes and hypertension. Similarly, these patients had the highest frequency of antitissue antibodies. In summary, the parameters of humural immunity were more changed in patients with two risk factors (diabetes and hypertension) compared to patients with only one risk factor. It is possible that these immunological changes appeared earlier than clinical symptoms of atherosclerosis and they could be used as an early prognostic test for predisposition to atherosclerotic vascular complications.