Adaptive Immunity In Patients Research Articles

Phenotypic features of innate and adaptive immunity in patients with chronic hepatitis C and end‐stage renal disease

The knowledge of the immunological profile of patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) on haemodialysis (HD) is still limited. This study investigated the immune response profile in HCV patients with concomitant ESRD focusing on the influence of the renal disease on the phenotypic profile of peripheral blood lymphocytes. Immunophenotypic features of peripheral blood leucocytes were assessed by flow cytometry in two distinct groups: HCV patients with ESRD (CHC+ESRD, n=16) and HCV patients with normal renal function (CHC, n=20). Two control groups that were included were as follows: HCV negative blood donors (BD, n=15) and HCV negative patients with ESRD (ESRD, n=19). Higher frequency of macrophage-like and pro-inflammatory monocytes along with enhanced frequency of CD3(-) CD16(-) CD56(+) , mainly CD56(dim) NK-cells, were the hallmark of CHC+ESRD patients. Lower frequency of B cells with significant decreased of B1 and CD23(+) B-cells were associated with ESRD, regardless the HCV infection. Although higher rates of activated CD4(+) and CD8(+) T cells were observed in the CHC and CHC+ESRD groups, the chemotaxis of T-cell subsets, based on their chemokine receptor expression, was affected by ESRD. Chronic hepatitis C patients with ESRD on HD exhibit distinctive phenotypic profile of circulating leucocytes. It may be implicated in the natural history of HCV infection in this particular group of patients and warrants further investigation.

Autophagy Attenuates the Adaptive Immune Response by Destabilizing the Immunologic Synapse

Variants in the genes ATG16L1 and IRGM affect autophagy and are associated with the development of Crohn's disease. It is not clear how autophagy is linked to loss of immune tolerance in the intestine. We investigated the involvement of the immunologic synapse-the site of contact between dendritic cells (DCs) and T cells, which contains molecules involved in antigen recognition and regulates immune response. DC autophagy was reduced using small interfering RNAs or pharmacologic inhibitors. DC phenotype and function were analyzed by confocal microscopy, time-lapse microscopy, and flow cytometry. We also examined DCs isolated from patients with Crohn's disease who carried the ATG16L1 risk allele. Immunologic synapse formation induced formation of autophagosomes in DCs; the autophagosomes were oriented toward the immunologic synapse and contained synaptic components. Knockdown of ATG16L1 and IRGM with small interfering RNAs in DCs resulted in hyperstable interactions between DCs and T cells, increased activation of T cells, and activation of a T-helper 17 cell response. LKB1 was recruited to the immunologic synapse, and induction of autophagy in DC required inhibition of mammalian target of rapamycine signaling by the LKB1-AMP activated protein kinase (AMPK) pathway. DCs from patients with Crohn's disease who had an ATG16L1 risk allele had a similar hyperstability of the immunologic synapse. Autophagy is induced upon formation of the immunologic synapse and negatively regulates T-cell activation. This mechanism might increase adaptive immunity in patients with Crohn's disease who carry ATG16L1 risk alleles.

Immunohistochemical analysis of molecular cell structures of genetic and adaptive immunityin patients suffering from psoriasis in the course of biological therapy

The author used the immunohistochemical method to study an effect of the biological modifier of immune reactions of Infliximab on immunopathogenetic mechanisms directly in the affected skin of patients suffering from psoriasis.

Regulation of TH17 and regulatory T cells in patients with Behçet disease

Behcet disease (BD) is a systemic inflammatory disorder with a diverse spectrum of clinical manifestations, including mucocutaneous, ocular, vascular, gastrointestinal, musculoskeletal, and central nervous system involvement. Although HLA-B51 is clearly defined as the major genetic risk factor, it can account for only a part of the genetic risk. BD is currently thought to be an autoimmune/autoinflammatory syndrome that is possibly induced by infections or other environmental factors. There are several hypotheses to explain the pathogenesis of BD. Recurrent orogenital ulcers,mucocutaneous acneiform-like lesions, and nondeforming arthritis typically present as episodes of unprovoked, recurrent inflammatory attackswith neutrophil-dominated infiltrates and resemble the recently named autoinflammatory disorders. Autoinflammatory disorders are disorders that typically respond to IL-1 antagonist therapies (which also seem towork in patients with BD). However, several studies also showed that polarization of CD4 T cells into TH1 cells and their cytokines, such as IFN-g and IL-12, play a central role in the pathogenesis of BD. Levels of IL-12, which drives the TH1 response in naive T cells, are increased in sera from patients with BD in correlation with the presence of TH1 lymphocytes. Tissue studies demonstrated TH1-type intestinal and cutaneous lesions, possibly drivenwith IL-12 and IL-23. A recent study also showed that natural killer type 2 cells, which produce IL-5 and IL-13, but not natural killer type 1 cells, which produce IFN-g and IL-10, were predominant in patients with BD in remission. However, as in the case of allergy and other autoimmune disorders, such as multiple sclerosis, only the TH1-TH2 paradigm cannot fully explain the full mechanism. The novel T-cell subsets TH9, TH17, TH22, and regulatory T (Treg) cells and their cytokines are intricately involved in inflammatory disorders.

Innate and adaptive immunity in patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal recessive syndrome characterised by chronic mucocutaneous candidiasis (CMC) and multiple endocrine failures. While the spectrum and modalities of autoimmunity are the main objects of current research into APECED, unequivocal data on the efficiency of immune responses to infectious agents are still elusive. The in vitro ability of monocytes and polymorphonuclear leucocytes to phagocytise and kill bacteria and fungi, and the degree of activation of lymphocytes cultured with mitogens and Candida albicans were investigated by flow cytometry in 11 APECED patients and healthy subjects. In addition, a comparison of gamma-globulin and immunoglobulin (Ig) concentrations was performed, and a correlation was sought between oral fungal load and the anti-Candida antibody titre. No difference between APECED patients and healthy subjects was observed in the phagocyte function, although the patients had a larger number of monocytes. Similarly, cultured lymphocytes were equally activated in the two groups. The concentration of gamma-globulins was higher among APECED patients, and anti-Candida IgM and IgG correlated with current and past oral candidiasis respectively. APECED patients have efficient innate and adaptive immune responses against exogenous stimuli, and currently, the mechanisms of mucocutaneous anergy leading to the high prevalence of CMC in this syndrome remain to be elucidated.