Altered Cell-mediated Immunity Research Articles

The inflammatory response to vaccination is altered in the elderly

To further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-γ, TNF-α, IL-6, IL-10) by whole blood cultures, circulating cytokines and acute phase proteins were analysed before and 2 days after vaccination. Prior to vaccination, only IFN-γ production was lower in the elderly than in the young subjects due to a lower mononuclear cell number. In the same time, although in the normal range, several acute phase proteins were greater in elderly than in young subjects, suggesting a low-grade inflammatory state in the elderly. After vaccination, IFN-γ production remained lower in the elderly than in the young, supporting an altered cell-mediated immunity with advancing age. TNF-α production was unaffected by either ageing or vaccination. IL-6 production was stimulated by vaccination in young subjects but not significantly in the elderly. IL-10 production was inhibited by vaccination in the elderly but not in the young. Acute phase proteins were less increased in elderly than in young subjects. Taken together, these results support a general lack of inflammatory response in the elderly exposed to an immune challenge and suggest that immune deficiency may concern both Th1 and Th2 responses. However, the interpretation must respect the limitation of small subjects number.

Differences in systemic and central nervous system cellular immunity relevant to relapsing–remitting multiple sclerosis

In order to elucidate the differences between systemic and central nervous system (CNS) immunity that are relevant to exacerbations of multiple sclerosis (MS), paired peripheral blood and cerebrospinal fluid (CSF) samples obtained from 36 non-treated patients with relapsing-remitting MS (RRMS) were simultaneously examined using flow cytometry to determine the percentages of functional lymphocyte subsets, as well as enzyme-linked immunosorbent assays for measuring soluble immune mediators. Active RRMS patients (n = 27) were characterized by an increase in CD4+ CXCR3+ Th1 cells in blood as compared with inactive patients (n = 9), and this parameter was inversely correlated with plasma levels of IL-10 and IL- 12p70. In contrast, an increase in the percentage of CD4+ CD25+ cells and a decrease in the percentage of CD8+ CD11a(high) cells were features of CSF samples from those with active RRMS. Further, CSF CD4+ CD25+ cells had a close association with leukocyte counts as well as albumin and CXCL10 levels in the CSF, and, thus, could be useful as a measure for inflammatory reactions in the CNS. On the other hand, CD8+ CD11a(high) cells may function as immunoregulatory cells, as their percentage in the CSF showed a positive correlation with CSF levels of the anti-inflammatory cytokine IL-4. These findings suggest that MS relapses occur in a combination with altered cell-mediated immunity that differs between the peripheral blood and CSF compartments, while measurement of lymphocyte subsets may be helpful for monitoring disease status.

Immunophenotypic Characterization of Peripheral Blood T-Lymphocytes and Their Subpopulations in Tuberculosis Patients before and after Treatments.

Tuberculosis is a chronic mycobacterial infection. The main effector cells against mycobacterium tuberculosis are CD4+ T lymphocytes. Our objective in this research was to evaluate the quantity of T lymphocytes and their subpopulations before and after treatments with combination of 4 drugs (Rifampcin, Isoniaside, pyrasinamide, Ethambutal) for 2 months directly in sputum-positive tuberculosis patients. Twenty patients as cases and twenty healthy people were selected as controls. Flow cytometry was used for TCD3+, TCD4+ and TCD8+ lymphocytes by using monoclonal antibodies. Our results indicated that there was alteration in cell mediated immunity during tuberculosis showing itself as decrease in TCD3+ and TCD4+ lymphocytes and increase in TCD8+ lymphocytes. The changes in TCD3+ and TCD4+ but not in TCD8+ were reversible after 2 months of treatment.

Altered Cell-mediated Immunity and Increased Postoperative Infection Rate in Long-term Alcoholic Patients

Preoperative alteration of T cell-mediated immunity as well as an altered immune response to surgical stress were found in long-term alcoholic patients. The aim of this study was to evaluate perioperative T cell-mediated immune parameters as well as cytokine release from whole blood cells after lipopolysaccharide stimulation and its association with postoperative infections. Fifty-four patients undergoing elective surgery of the aerodigestive tract were included in this prospective observational study. Long-term alcoholic patients (n = 31) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for either alcohol abuse or alcohol dependence. The nonalcoholic patients (n = 23) were defined as drinking less than 60 g ethanol/day. Blood samples to analyze the immune status were obtained on morning before surgery and on the morning of days 1, 3, and 5 after surgery. Basic patient characteristics did not differ between groups. Before surgery, the T helper 1:T helper 2 ratio (Th1: Th2) was significantly lower (P < 0.01), whereas plasma interleukin 1beta and lipopolysaccharide-stimulated interleukin 1ra from whole blood cells were increased in long-term alcoholic patients. After surgery, a significant suppression of the cytotoxic lymphocyte ratio (Tc1:Tc2), the interferon gamma:interleukin 10 ratio from lipopolysaccharide-stimulated whole blood cells, and a significant increase of plasma interleukin 10 was observed. Long-term alcoholics had more frequent postoperative infections compared with nonalcoholic patients (54%vs. 26%; P = 0.03). T helper cell-mediated immunity was significantly suppressed before surgery and possibly led to inadequate cytotoxic lymphocyte and whole blood cell response in long-term alcoholic patients after surgery. This altered cell-mediated immunity might have accounted for the increased infection rate in long-term alcoholic patients after surgery.

AM3 (Inmunoferón®) as an adjuvant to hepatitis B vaccination in hemodialysis patients

Patients with end-stage renal disease (ESRD) undergoing hemodialysis have severe alterations in cell-mediated immunity (CMI) that increases their risk of contracting chronic hepatitis B virus (HBV) infection and decreases their protective responses to HBV vaccine. In an effort to improve the humoral response to an accelerated HBV vaccine protocol in these patients, the ability of an immunomodulator, AM3, to improve seroconversion was investigated. A total of 269 patients were enrolled in a multicenter trial. All patients received a DNA recombinant vaccine (40 microg HBsAg/dose/day) on days 0, 10, 21, and 90. AM3 or placebo (3 g/day) was given orally for 30 consecutive days beginning 15 days prior to the first vaccine dose. Anti-HBsAg titers were measured on days 120 and 270 after the beginning of the trial. After one month, 207 patients could be evaluated and 132 patients after six months. The placebo and AM3-treated groups had comparable seroconversion and protective response rates one month after the final vaccine dose. The AM3 treatment group, but not the placebo group, maintained these protective titers up to six months after the final vaccine dose. At this time, the percentage of high responders (anti-HBsAg>100 IU/L) and mean anti-HBsAg titers in the AM3 group was significantly higher than in the placebo group. AM3 is a safe and easily tolerated oral agent that potentiates long-term serological immunity to hepatitis B in hemodialysis patients after vaccination.

Herpes simplex viruses.

Herpes simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with herpes simplex encephalitis. The use of HSV for gene therapy heralds a new era of herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.

Evidence for altered cell-mediated immunity in postmastectomy lymphoedema

Patients with chronic lymphoedema are prone to develop chronic infections and various tumours in the lymphoedematous limb, suggesting that regional immune surveillance is impaired. To test the hypothesis that cutaneous cell-mediated immunity is impaired, 35 women with postmastectomy lymphoedema were investigated using dinitrochlorobenzene to test the afferent and efferent loops of the allergic contact immune response. The results support the role of lymphatics as an important component of the immune response to allergens by the demonstration of impairment of both the afferent and efferent loops of the allergic contact dermatitis reaction, and confirm that there is suppression of immune competence in a lymphoedematous limb.

Evidence for altered cell-mediated immunity in postmastectomy lymphoedema

Evidence for altered cell-mediated immunity in postmastectomy lymphoedema

Immunologic findings in peyronie's disease: a controlled study

Objectives Recent literature suggests the hypothesis of an immune etiology of Peyronie's disease. In this controlled study, the immune response pattern of the disease is investigated. Methods Sixty-six patients with Peyronie's disease and 20 age-matched controls were studied. In all patients, skin test (multitest), in vitro lymphocyte transformation test (LTT), serum immunoglobulin (lg) A, G, and M, anti-DNA, antinuclear and anti-smooth muscle cell antibodies, C3 and C4 complement fractions, antistreptolysin, and C-reactive protein titers were evaluated. Results A fair percentage (75.8%) of the patients with Peyronie's disease exhibited at least one abnormal immunologic test, in comparison to only 10% among controls (chi-square = 27.8, df = 1; P < 0.0001). Alterations of cell-mediated immunity (multitest, LTT) were observed in 48.5% of patients, alterations of humoral immunity (lg) in 31.8%, and alterations of markers of autoimmune disorders (autoantibodies, complement activation) in 37.9% of the cases. Conclusions Our results support the hypothesis that there is some involvement of the immune system in the pathogenesis of Peyronie's disease, although the available data still appear to be insufficient to formulate a definite pathogenetic hypothesis.

Stabilized analogs of thymopentin. 3. Evaluation of ketomethylene pseudopeptides for antiarthritic properties.

This study analyzed the role of ketomethylene pseudopeptides of thymopentin as potential agents for the treatment of arthritis. The analogs were tested in vivo using assessment of inflammation and antibody production in the mouse type II collagen arthritis model and the rat adjuvant arthritis model. The compounds were also tested for immune-potentiating activity in vitro using induction of the lymphocyte marker, Thy-1.2, in mouse spleen cells and stimulation of T-cell proliferation. The results show that certain of the compounds exhibit disease-remitting properties for arthritis as evidenced by reduction of paw swelling in the mouse and rat models and decreased incidence of disease in the mouse model. The active compounds were dose specific and represented a range in efficacy. In spite of effects on arthritis, type II collagen antibody levels were not altered in the mouse model. Selected compounds also exhibited immune potentiating properties as evidenced by induction of Thy-1.2 expression and stimulation of T-cell proliferation. The absence of effect of the compounds on type II collagen antibody production suggests that the antiarthritic activity of the effective compounds results from alteration of cell-mediated immunity.

Acyclovir for the prevention and treatment of varicella zoster in children, adolescents and pregnancy.

Varicella causes a mild, self-limiting childhood disease that may reactivate years later as shingles. In immunocompromised patients with altered cell mediated immunity, and rarely in healthy individuals, varicella results in a life-threatening infection. The antiviral drug, acyclovir, substantially reduces the mortality and risk of severe disease in these groups of patients. Early commencement of acyclovir is recommended for children with both varicella and altered cell mediated immunity, newborns during the first 2 weeks of life, preterm infants in the neonatal nursery, and severe varicella or shingles (including ocular zoster) in any patient, as well as during pregnancy. Acyclovir may be considered in children with serious cardiopulmonary disease or chronic skin disorders where varicella may exacerbate the underlying disease or increase the risk of secondary bacterial sepsis. Acyclovir, however, is not recommended for healthy individuals without severe disease, as a prophylactic agent against varicella, for asthmatics receiving aerosolized or low-dose oral steroids and/or as treatment of the post-varicella syndromes. When acyclovir is prescribed it should be given intravenously to those with severe disease, those at risk of dissemination and in children younger than 2 years of age.

74-Year-Old Woman With Dyspnea, Fever, and Cough

74-Year-Old Woman With Dyspnea, Fever, and Cough

Interleukin-2 and interleukin-6 in schizophrenia and mania: Effects of neuroleptics and mood stabilizers

There is some evidence that schizophrenia may be accompanied by alterations in cell-mediated immunity (CMI) and that antipsychotic agents may modulate CMI. The purpose of this study was to investigate the plasma levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sIL-2R, and transferrin-receptor (TfR) in schizophrenia and mania, and the effects of treatment with neuroleptics or mood stabilizers on these variables. The subjects were 14 schizophrenic patients, 10 manic patients and 21 healthy volunteers. The above immune variables were measured in baseline conditions and after treatment with neuroleptics in schizophrenic patients and valproate in manic patients. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were significantly higher in the combined group of psychotic patients than in healthy volunteers. Plasma IL-6 was significantly higher in schizophrenic patients, while plasma sIL-6R and sIL-2R were significantly higher in mania than in normal controls. In schizophrenic patients, plasma levels of IL-6, sIL-6R and TfR were significantly lower after treatment with neuroleptics than before treatment. No significant effects of valproate on the immune-inflammatory markers could be found in the manic patients. It is suggested that activation of CMI may occur in both schizophrenia and mania and that neuroleptics may have immunosuppressive effects through suppression of IL-6 or IL-6R-related mechanisms.

Effects of Naloxone Opiate Blockade on the Immunomodulation Induced by Exercise in Rats

The purpose of this study was to examine the possible involvement of the endogenous opiate system in the changes in immune competence induced by isolated exercise. Male untrained rats were subjected to a 2.5 hours swimming exercise bout. Animals were killed 15 min after the end of the exercise. The concentration of leukocytes, lymphocytes, monocytes and granulocytes and T4 (T-helper), T8 (T-suppressor/cytotoxic), interleukin-2 receptor (IL-2R) and transferrin receptor (TrfR) positive lymphocytes were determined both in peripheral blood and spleen by flow cytometric analysis. Exercise resulted in a significant decrease in 1) blood lymphocyte and splenic granulocyte number (p < 0.05), 2) blood and splenic T4 positive lymphocytes and T4/T8 ratio (p < 0.05), and 3) blood and splenic IL-2R and TrfR positive lymphocytes (p < 0.05). The injection of the opiate blocker naloxone to exercising rats induced a decrease in the concentration and proportion of T8 positive lymphocytes, thereby restoring a normal T4/T8 ratio both in peripheral blood and spleen. Naloxone had no effect in control animals. The concentration and proportion of IL-2R and TrfR positive lymphocytes were not affected by naloxone. The mechanisms of the immunomodulation induced by isolated intense exercise are unclear. These data suggest that endogenous opiates participate in the alteration of cell-mediated immunity associated with exercise by modulating the T8 (suppressor/cytotoxic)-cell activity.

Herpes simplex virus tracheitis in a patient with the acquired immunodeficiency syndrome

Herpetic tracheobronchitis and pneumonia occur basically in immunodepressed patients, but have rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). Some large reviews on pulmonary manifestations in AIDS report a small number of herpetic pulmonary infections, without determining any prevalence of this particular viral involvement. Predisposing factors are alteration of cell-mediated immunity and invasive procedures (such as endotracheal tube use) in debilitated patients. The case we report illustrates the occurrence of a herpetic tracheitis in an HIV-infected patient with severe P. carinii pneumonia, needing systemic corticotherapy and mechanical ventilation. It illustrates the risk of dissemination of herpes simplex virus (HSV) from a herpetic stomatitis to the lower respiratory tract, even after the endotracheal cannula has been removed.

Alteration of the immune system in burns and implications for therapy.

Following thermal injury profound alterations occur in the arachidonic acid cascade, and the cytokine cascade. There are further alterations in cell mediated immunity affecting all cells of the immune system, and the neuro endocrine axis. There are profound changes in humoral immunity as well. Experimental approaches to alterations in the above systems indicate that success can be obtained in restoring normality of any individual alteration in a suitable experimental model. However, before clinical intervention can be successful, it is likely that a combination of interventional mordalities will need to be used.

Urinary neopterin quantification indicates altered cell-mediated immunity in healthy subjects under psychological stress.

In an effort to quantify changes in cell-mediated immunity (CMI) in healthy subjects under stress, we measured levels of neopterin, a well-validated marker of CMI activation, in the urine of medical students undergoing academic examinations. Neopterin/creatinine ratios measured on the first day of examinations (mean 46 mumol/mol) were significantly lower than those measured two weeks before (mean 78 mumol/mol, p = .004). Minimum neopterin production coincided with maximum subjective stress, as measured by a visual analogue scale. After examinations, neopterin/creatinine ratios rose (means 62 mumol/mol immediately after, and 65 mumol/mol two weeks after examinations), and these levels were not statistically different from those two weeks before examinations. Over this post-examination period, subjective distress was significantly lower than at either time point before examinations. We conclude that urinary neopterin/creatinine ratios may change significantly during periods of psychological stress, indicating concomitant alterations in CMI activation.

Chloroquine-induced exacerbation of psoriasis may occur because of altered cell-mediated immunity.

Chloroquine-induced exacerbation of psoriasis may occur because of altered cell-mediated immunity.

Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia

Neopterin is a validated marker of the activation of cell-mediated immunity in a variety of disease states. We measured neopterin and creatinine concentrations in the plasma and urine of 22 schizophrenic and 26 depressed patients admitted acutely to hospital, and compared results with those in a large group of normal controls. Neopterin/creatinine ratios were normal in the schizophrenic patients, but significantly elevated in the plasma of depressed patients. In each diagnostic group, the use of psychotropic drugs before admission had no effect on the neopterin ratios observed. Our findings indicate altered cell-mediated immunity in depression.

Herpes simplex virus infection in the immunocompromised cancer patient.

The development of infection remains a significant source of morbidity and mortality in the oncology patient. This patient population is at increased risk for infection because of alterations in cell-mediated immunity generated by the underlying neoplastic process and/or immunosuppressive therapy. Viral infection, particularly that attributable to herpes simplex virus (HSV), is being seen with increased frequency in the oncology patient. Because effective therapy is available with the early use of antiviral agents, it is important to be aware of the potential for viral infection and to recognize the signs and symptoms that are evident early in its course. An overview of HSV infection is provided here, including discussion of the virus itself, its pathogenesis, its clinical spectrum, and current prophylactic and therapeutic approaches.