No specific mRNA expression was found in the challenged skin of negative elicitation reactions, also indicating no sign of active down-regulation. The study contibutes strongly to the evidence of a decreased susceptibility to develop contact allergy in individuals with autoimmune diseases such as psoriasis. Interestingly, recent epidemiological studies have

shown that an inverse relation exists between contact allergy and the autoimmune diseases: psoriasis, diabetes type I, rheumatoid arthritis and inflammatory bowel disease [1–4]. Two experimental sensitization studies have shown reduced reactivity to challenge in patients with psoriasis [5,6], but Alvelestat concentration the ability to become sensitized was not investigated. One study has found a reduced sensitization ratio among patients with rheumatoid arthritis [7], but the sensitization ratio and reactivity of patients with other autoimmune diseases have not been investigated and the mechanisms behind the apparent impairment in contact allergy remain unknown. Contact allergy is highly

regulated, due in part to regulatory T cells playing a role in diminishing collateral damage and helping in the resolution of allergic contact dermatitis (ACD). Regulatory T cells may even help in preventing ACD altogether, indicated by recent studies showing that in non-allergic individuals antigen-specific regulatory T cells are activated and found in the challenge sites Selleck ICG-001 and blood of non-allergic individuals [8,9]; thus, an active down-regulation is taking place. The aim of our study was, first, to investigate in a controlled human sensitization study the ability of becoming sensitized among patients with two different autoimmune

many diseases, psoriasis and diabetes type I, and secondly to identify whether or not down-regulatory events were present in the elicitation phase by investigating skin biopsies taken from elicitation sites with immunohistochemistry and mRNA expression profiles with microarray analysis. Sixty-eight adult patients were included in the study: 23 patients with psoriasis (13 women, 10 men, mean age 50·7 years), 22 patients with diabetes type I (10 women, 12 men, mean age 40·0 years) and 23 healthy controls (14 women, nine men, mean age 34·6 years). Patients with psoriasis were recruited from the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark. Patients with diabetes were recruited from Steno Diabetes Centre, Gentofte, Denmark and healthy controls via advertisement. Inclusion criteria were: (i) age between 18 and 65 years of age; and (ii) for psoriasis patients, a diagnosis of psoriasis verified clinically by a specialist in dermatology and for diabetes patients a diagnosis of type I insulin-dependent diabetes.

So far interferon-γ (IFN-γ) is the only

cytokine known to induce aberrant RB through the initiation of tryptophan breakdown (Wyrick, 2010). Cells bearing aberrant bodies were even resistant to apoptosis (Dean & Powers, 2001). The resistance to apoptosis is of considerable relevance, because the aberrant bodies are still producing chlamydial proteins, such as Hsp60, that can elicit a sustained and significant inflammatory response even without bacterial replication. These aberrant bodies were mainly observed in vitro. Nonetheless, Chlamydia can also persist in vivo, but the mechanism is still mostly unknown (reviewed in Wyrick, 2010). The role and activation of several innate immune response components by Chlamydiales as well as the possible damage caused by them will be described in more detail in the following paragraphs. Cytokines EPZ 6438 are usually only transiently BMN 673 chemical structure expressed in response to a pathogenic challenge. Due to their pleiotropic nature, it is difficult to determine as to which response

is more relevant for the outcome of an infection. Cytokines can be separated into three functional classes: mediators and regulators of innate immunity or adaptive immunity and stimulators of hematopoesis. For this review, we will consider mainly the cytokines involved in innate immunity, more precisely the ones elicited upon chlamydial infection. Two main regulatory and pro-inflammatory cytokines triggered by microbial infections are tumor necrosis factor (TNF-α) and interleukin 1 (IL-1). Both are mostly expressed by mononuclear phagocytes, although IL-1 can also be expressed by epithelial cells, endothelial cells and fibroblasts. They stimulate the secretion of other cytokines and have a Protein kinase N1 chemokine function for neutrophils, monocytes and leukocytes. There are two forms of IL-1 (α and β), which are only 30% homologous, but they bind to the same receptor and have the same biological function (Dinarello, 2009). However, IL1-α is secreted only by dying cells compared with IL1-β. Also IL-1α is constitutively expressed by epithelial cells, while IL-1β is not (Dinarello, 2009). Other chemokines of interest are growth-related oncogenes and IL-8. The latter is a strong pro-inflammatory

chemokine that attracts neutrophils. It is produced by many different cell types and can also activate neutrophil functions. In the mouse model, there are only two functional homologs for IL-8: macrophage inflammatory protein (MIP-2) and keratinocyte chemoattractant (KC) (Iizasa & Matsushima, 2000). IL-12 plays an important role in innate immunity by activating IFN-γ. It also induces the differentiation of naïve CD4+ T helper into mature TH1 cells. IL-10 has an antagonistic function to IL-12 and IL-8 by inhibiting their production as well as those of other components of the immune response. It is produced by macrophages and T cells and prevents an overactivation of the immune system through its negative feedback on the pro-inflammatory cytokines.

We incubated the purified protein with tributyrin to examine its activity. We performed incubation at 37°C for 6  hrs, after which we analyzed the reaction mixture by TLC. As shown

in Figure 3, the spot for tributyrin diminished in size in proportion to the amount of purified protein in the reaction mixture, indicating that the purified protein possesses the ability to hydrolyze tributyrin. Next, we examined the esterase activity of the purified protein using the following pNp-fatty acyl esters as substrates; decanoate (C10), palmitate (C16) and stearate (C18). These substrates were hydrolyzed by the purified protein; however, with respect to fatty acid specificity, the purified protein was effective at cleaving esters containing short chain fatty

acids. The efficacy of the purified protein in cleaving the esters containing long-chain fatty acid was low (Fig. 4). These results show that the purified protein is a lipase. To examine the click here effect of the reaction temperature on the esterolytic activity of the purified protein, the purified protein was incubated with pNpp at various LGK-974 research buy temperatures. The volume of reaction mixture was 200 μL and 1 μg purified protein was dissolved in the mixture. The purified protein exhibited maximum activity when the reaction was processed at 55°C (Fig. 5a). In order to examine thermostability, the solution containing purified protein (1 μg/20 μL) was heated for Rebamipide 10  min at the temperatures indicated in Fig. 5b. Subsequently, the esterolytic activity of the heat-treated sample was assayed at 37°C. We found that the lipase was stable up to 60°C (Fig. 5b). Heat treatment at higher temperatures resulted in loss of activity. The genome sequence of A. hydrophila ATCC7966 has been determined and the extracellular lipase gene was found to be encoded in the AHA0104 locus (GenBank, accession number CP000462) (27). Homology research showed that the amino acid sequence of the extracellular lipase of A. hydrophila ATCC7966 is almost identical to that of the phospholipase A1 reported by Merino et al. (11). The identity between the two

lipases is 99.5%. Referring to these sequences, we determined the whole sequence of the lipase of A. sobria 288, and registered the nucleotide sequence with GenBank (accession number JN019936). The amino acid sequence deduced from the nucleotide sequence is shown in Figure 6. As described, the sequence of the five amino acid residues from the amino terminus is GGDDN, identical to that from the 19th residue of the amino acid sequence deduced from its nucleotide sequence (Fig. 6). The sequence contains a lipase-substrate binding signature sequence, GLKVHFLGHSLGA, at the site from the 561st to 573rd positions of the sequence (Fig. 6) (28). The theoretical average molecular weight deduced from the amino acid sequence of the region from the 19th amino acid residue to the carboxy terminal end is 81,135.7.

This study was supported by National Nature Science Foundation of China grant 81070766 to Ze Zhang Tao, and a Young Foundation of Hubei University of Science and Technology grant (KY10058) to Shui Bin Wang. Shui Bin Wang is

the main writer. Ze Cheng and Bo Kui Xiao performed the main animal experiment and gained the preliminary data. Yu Qin Deng performed English interpretation and correction of the manuscript and performed find more the statistical analysis. Jie Ren performed the production of image. Ze Zhang Tao designed the whole study and is responsible for the study. There is no conflict of interest related to this study. “
“The molecular definition of major histocompatibility complex (MHC) class I-presented CD8+ T-cell epitopes from clinically relevant Mycobacterium tuberculosis (Mtb) target proteins will aid in the rational design of T-cell-based diagnostics of tuberculosis (TB) and the measurement of TB vaccine-take. We used an epitope CH5424802 cell line discovery system, based on recombinant MHC class I molecules that cover the most frequent Caucasian alleles [human leucocyte antigen (HLA)-A*0101,

A*0201, A*0301, A*1101, A*2402, B*0702, B*0801 and B*1501], to identify MHC class I-binding peptides from overlapping 9-mer peptides representing the Mtb protein TB10.4. A total of 33 MHC class I-binding epitopes were identified, spread across the entire amino acid sequence, with some clustering at the N- and C-termini of the protein. Binding of individual peptides or closely related peptide species to different MHC class I alleles was frequently observed. For instance, the common motif of xIMYNYPAMx bound to six of eight alleles. Affinity (50% effective dose) and PJ34 HCl off-rate (half life) analysis of candidate Mtb peptides will help to define the conditions for CD8+ T-cell interaction with their nominal MHC class I-peptide ligands. Subsequent construction of tetramers allowed us to confirm the recognition of some of the epitopes by CD8+ T cells from patients with

active pulmonary TB. HLA-B alleles served as the dominant MHC class I restricting molecules for anti-Mtb TB10.4-specific CD8+ T-cell responses measured in CD8+ T cells from patients with pulmonary TB. Tuberculosis (TB) is a major health problem world-wide; increasing resistance and coinfection with the human immunodeficiency virus (HIV) lead to an increased disease burden in many countries. Although anti-mycobacterial drugs and a vaccine, Bacillus Calmette–Guérin (BCG), are available, neither has proved to be the solution in controlling the disease. The immune mechanisms controlling Mycobacterium tuberculosis (Mtb) are not fully understood, but it is known that both the innate and adaptive parts of the immune system are involved in Mtb control,1 and cell-mediated immunity, involving both CD4+ and CD8+ T cells, has been shown to be important for effective Mtb containment.

In the next subsections, we will illustrate the protective effects mediated by Ab–FcR interactions in the context of a selection of infections with intracellular bacteria and parasites. Legionella pneumophila are Gram-negative bacteria that, when inhaled, can infect and replicate within alveolar macrophages and cause a severe form of pneumonia known as Legionnaire’s disease. Upon contact with the macrophage, L. pneumophila uses its Icm/Dot type IV secretion system (T4SS)

to inject a large number of effector proteins into the cytosol of the PI3K inhibitor cancer host cell 63. This promotes phagocytosis and modulates trafficking within the host cell, resulting in the evasion of phagolysosomal fusion and the establishment of a replication-permissive vacuole 64. We have recently shown that this Icm/Dot T4SS-mediated subversion of trafficking within the host cell does not take place in the presence of specific Abs as, in such circumstances, L. pneumophila is targeted to lysosomes and can no longer replicate intracellularly 65. Thus, opsonized L. pneumophila are targeted selleck chemicals llc into

degradative pathways, indicating that specific Abs can effectively oppose the events initiated by the T4SS. The opsonization of L. pneumophila with specific Abs does not interfere with the function of the T4SS itself but it is actually the cross-linking of activating FcRs on the surface of macrophages that renders these host cells nonpermissive for intracellular replication of L. pneumophila. The importance of FcR triggering for this protective effect was demonstrated both in vitro and in vivo; however, the lysosomal targeting of L. pneumophila is not simply a direct consequence of FcR-mediated endocytosis and subsequent phagolysosomal fusion since macrophages, which had received an FcR trigger before infection with nonopsonized bacteria, also effectively targeted L. pneumophila to lysosomal compartments and hence did not permit

their intracellular replication 65. These P-type ATPase results suggest that FcR cross-linking induces a signaling cascade that effectively counteracts the modulation of host cell trafficking by Legionella effectors and redirects the bacteria to lysosomes where they are degraded. By arresting phagosome maturation M. tuberculosis survives and replicates in membrane-bound compartments in macrophages 66. Ab responses have long been believed to play a negligible or even detrimental role in protection against this intracellular bacterium, whereas cell-mediated immunity was assigned to be crucial in resolving infections. Nevertheless, newer findings implicate a role for Abs in protection against mycobacterial infections 67, 68. mAbs of the IgG3 or IgG1 subclass recognizing surface Ags of M. tuberculosis such as the carbohydrate lipoarabinomannan (LAM) have been shown to prolong survival of intratracheally or intravenously M.

For example, the regulator of calcineurin 1 (RCAN1) is a transcription factor that inhibits signal transduction mediated by the nuclear factor of activated T cells (NFAT) [58], and has been shown to reduce inflammatory responses in mice by stabilizing an inhibitor of nuclear factor-kappa B cells (NF-κB) [59]. Two possible causes of secondary immunodeficiency, accelerated ageing and https://www.selleckchem.com/products/nutlin-3a.html zinc deficiency, have been explored further. Because of the senescence associated to neurological conditions in DS such as premature Alzheimer’s disease [60] a similar ageing process in the immune system has been suggested, including mechanisms of increased apoptosis [61,62], that could be responsible for the observed lymphopenia and

immune dysfunction. The deficiency of plasma zinc levels observed in some DS subjects and the need of zinc for SOD activity have been proposed as mechanisms of immunological abnormalities. Cocchi and colleagues [25] tested

if zinc deficiency might be only transient, and p38 MAPK phosphorylation found that plasma levels of zinc decrease over time after 5 years of age. However, observational studies examining zinc levels and immune status and clinical trials of zinc supplementation have failed to show a consistent clinical benefit [63–65]. DS children might have symptoms of chronic rhinitis and reactive airway disease, suggesting hypersensitivity to inhaled allergens. A study comparing positivity to skin prick hypersensitivity test between symptomatic DS children and age-matched controls found that 18% of cases had at least one positive allergen in the skin test, which contrasts with 54% of non-DS controls [66]. The authors conclude that allergen sensitization is not a major contributor of respiratory illnesses in DS children. Vestergen et al. [31] found only six of 44 DS

patients with elevated IgE, and none of 28 DS individuals tested had an allergen identified as a trigger for allergy symptoms. Despite the multiple immunological abnormalities outlined above, it is still unclear whether these are the major determinants Mannose-binding protein-associated serine protease of increased risk of infections in DS children. This susceptibility to infections is probably enhanced by other co-morbidities that weaken mucosal barriers; for example, abnormal airway and ear anatomy, macroglossia, congenital heart disease and reactive airway disease or an inability to handle secretions. Anatomical abnormalities of the airways may impair clearance of secretions and facilitate infections. Bertrand et al. [67] described airway anomalies among 75% of DS children and 35% of non-DS children with recurrent respiratory symptoms who underwent fibreoptic bronchoscopy. The most common abnormality seen in both DS and non-DS groups was laryngomalacia, with 50% incidence in the DS group compared to 19% in the non-DS group. Tracheomalacia and tracheal bronchus were also observed. Evidence of pulmonary hypoplasia associated to DS has also been reported [68,69].

RYUGE AKIHIRO, OZEKI TOSHIKAZU, MINATOGUCHI SHUN, MURAI YUKARI, KAWATO RUI, OZEKI TAKAYA, OYAMA YUKAKO, NOMURA ATSUSHI, TOMINO TATSUHITO, SHIMIZU HIDEAKI, FUJITA YOSHIRO Chubu-Rosai Hospital Introduction: There are few reports concerning tumor lysis syndrome arising from autolysis Obeticholic Acid cost of solid cancers.

We describe a recently encountered case of tumor lysis syndrome detected during detailed examination of lung cancer with liver metastasis. Methods & Results: The patient was a 79-year-old male. He was being managed at the Department of Nephrology of our hospital because of chronic kidney disease (Cr: 2.5 mg/dl). Early in April of XXXX, he developed pain involving the right hypochondrial region and anorexia. Because of intense malaise, he visited the outpatient critical care unit of our hospital on April 6. At that time, blood tests revealed marked elevation of

hepatobiliary enzymes, and CT scan disclosed a tumorous lesion approximately 13 cm in size in the right lobe of the liver. He was thus hospitalized to undergo detailed examination. Liver biopsy was performed on the 11th hospital day. Around April 15, his urine volume began to decrease, and blood tests the following day revealed elevation of BUN (60.0 mg/dl) and Cre (3.67 mg/dl), accompanied BGB324 ic50 by uric acid elevation (22.2 mg/dl). Renal function did not improve despite fluid therapy. Hemodialysis was thus started on April 18. Thereafter, the uric acid level decreased but urine volume showed no improvement and his general condition gradually deteriorated. The biopsy results allowed a diagnosis of small-cell carcinoma, suggesting that the nodular shadow noted in the right lung represented the primary Acyl CoA dehydrogenase tumor. Treatment

was judged to be difficult in view of his general condition, and the patient was followed without active treatment. He died on April 23. Conclusion: We thus encountered a case of tumor lysis syndrome probably arising from autolysis of small-cell lung carcinoma and an associated metastatic hepatic lesion. RYU HAN JAK1, HAN IN MEE1, HAN JI SUK1, PARK JUNG TAK1, YOO TAE-HYUN1,2, KANG SHIN-WOOK1,2, MOON SUNG JIN3, OH HYUNG JUNG1 1Department of Internal Medicine, College of Medicine, Yonsei University, Seoul; 2Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul; 3College of Medicine, Kwandong University, Gyeonggi-do, Korea Introduction: Platelet size has been demonstrated to reflect platelet activity and to predict poor clinical outcomes in patients with cardiovascular disease. However, the prognostic value of platelet size for mortality has not been studied in patients with acute kidney injury (AKI). Methods: A total of 349 patients who received continuous renal replacement therapy (CRRT) for AKI between August 2009 and October 2011 were divided into two groups based on the median mean platelet volume (MPV) at the time of CRRT initiation.

Either the volunteer or a relative gave their written informed consent, and the study was approved by the ethical committee of Hospital District of Southwest Finland. Exclusion criteria were the consumption of antibiotics in the last selleck compound library month and use of medication expected to either affect the immune function and/or the intestinal microbiota of the subject. Another exclusion criterion was the habitual use of pro- and/or prebiotic-containing products. The study protocol consisted of three consecutive phases. In phase 1, the subjects

consumed a control cheese during breakfast for 2 weeks (run-in). In phase 2, the subjects consumed a probiotic cheese for 4 weeks (intervention). In phase 3, the subjects consumed the same control cheese selleck again for 4 weeks (wash-out). The products were blinded to the volunteers and were identical in taste and appearance. The total duration of the study was 10 weeks, and during the time, the food at the elderly home remained stable. Heparinized peripheral blood (9 mL) was drawn by a venipuncture from each subject at baseline (T0), after run-in (T1), after intervention (T2), and after wash-out (T3) for immunological analysis. On the same occasion, a blood sample was collected for general health monitoring tests carried out at the University of Turku Hospital. The probiotic and the control Gouda cheese were commercial products (Mills DA, Oslo, Norway). Identical slices

of both types of cheese (15 g) were prepared and packed before the commencement of the study. The probiotic cheese slice contained approximately 109 CFU of L. rhamnosus HN001 (AGAL NM97/09514) and L. acidophilus NCFM (ATCC 700396). The viability of the strains was assessed throughout the study and was observed to remain stable. Both probiotic and control cheese contained proprietary starter strains (Choozit 712™, Danisco, Paris). The volunteers consumed one slice of cheese per day during breakfast. The probiotic cheese had been on the Norwegian

market for approximately 1 year. The probiotic strains Palmatine have been in commercial use for approximately 7 years (L. rhamnosus HN001) and 30 years (L. acidophilus NCFM) and have substantial safety and efficacy data (Shu et al., 1999; Zhou et al., 2000; Gill & Rutherfurd, 2001; Sanders & Klaenhammer, 2001; Sheih et al., 2001). The same probiotic cheese was tested for bacterial survival using a human gastrointestinal tract-simulating model, and it was shown that the strains (L. acidophilus NCFM and L. rhamnosus HN001) survived the simulated upper gastrointestinal tract (Makelainen et al., 2009). The cytotoxicity of the peripheral blood mononuclear cells (PBMCs), proportions of CD3−CD56+ cells (NK cells), CD3+CD56+ cells (NKT cells), CD3+CD56− cells, and CD3−CD56− cells in the total PBMCs, and phagocytic activity were assessed using flow cytometry (FACScan flow cytometer, BD biosciences). The data were analyzed using cellquest pro software.

At present, the emergence of non-albicans Candida spp. causes serious infections that

are difficult to treat the human populations worldwide. The available, synthetic antifungal drugs show high toxicity to host tissues causing adverse effects. Many metabolites of terrestrial and marine plants, microbes, algae, etc., contain a rich source of unexplored novel leads of different types, which learn more are under use to treat various diseases. Such natural drugs are less expensive and have lower toxicity to host tissues. The patent search on identified and potential anticandidal-lead molecules, from various patent databases, has been described in this review. Furthermore, this article consolidates the trends in the development of anticandidal drug discovery worldwide. Most of the investigations on natural, bioactive molecules against candidiasis are in various phases of clinical trials, of which, two drugs Caspofungin acetate and Micafungin sodium were approved by the U.S. FDA. In conclusion, the exploration of drugs from natural resources serves as a better alternative source

in anticandidal therapeutics, having great scope for drug discovery in the future. “
“A ‘trailing’ effect has been commonly observed when azole antifungals are tested against Candida spp. Previous experience with fluconazole indicates that 24-h minimum inhibitory concentration (MIC) values are more compatible endpoints when compared with clinical outcomes. We evaluated Fulvestrant the trailing effect of Candida isolates tested with itraconazole in a guinea pig model of systemic

candidiasis. Survival and organ burden were only significantly affected by using a higher dose of itraconazole, irrespective of the MIC differences at 24 and 48 h. A fluconazole-resistant strain with susceptible dose-dependent MICs to itraconazole was successfully treated with high-dose itraconazole. Our data suggests that survival and microbiological response depend more on drug dosing than on the trailing phenotype of the isolates. “
“To correlate fluconazole and nystatin susceptibility with clinical outcome for complicated vulvovaginal candidosis Thymidine kinase (VVC), 287 Candida isolates were collected from 283 patients with complicated VVC. In vitro fluconazole and nystatin susceptibility was tested using E-test or commercial agar diffusion method. The patients were treated with fluconazole or nystatin. The fluconazole-resistant and -susceptible dose-dependent (SDD) rates of Candida species were 0.8% (1/132) and 5.3% (7/132) respectively. The mycological cure rate at days 7–14 and days 30–35 in fluconazole SDD isolates was lower than that in fluconazole-susceptible isolates (42.9% vs. 88.7% and 28.6% vs. 76.6%, P < 0.05). The mycological cure rate at days 7–14 and days 30–35 in VVC caused by Candida albicans and non-albicans Candida species was 85.6% (219/256) vs. 88.9% (24/27) and 79.3% (203/256) vs. 81.5% (22/27), P > 0.05. All C.

[7, 8] Amino acid sequence at the N-terminus of both chains varies greatly among different Roxadustat in vitro antibodies, whereas the C-terminal sequence remains strikingly similar.[9] These two regions are referred to as the variable (V) and constant (C) regions, respectively. The V region composed of 110–130 amino acids, gives the antibody its specificity for binding to antigen. The exon encoding the variable region is assembled from two (or three) individual gene segments,[2, 10] which are classified

into variable (V),[11] diversity (D) (present only in immunoglobulin heavy chains, not in the light chains)[12-14] and joining (J)[15, 16] regions (Fig. 1). To obtain a functional variable region, recombination between D and J occurs to give a DJ segment, followed by another recombinational event involving V to yield the final V(D)J fragment. The germline consists of multitudes of V, D and J gene segments and random recombination among these results in the generation of approximately 106 different combinations, accounting for the dramatic expansion in the variability

of the sequence (Fig. 1). The TCR is structurally similar to the antigen-binding fragment [F(ab)] of the antibody. Similar to the antibodies, it has two glycoprotein subunits and each is encoded by a somatically rearranged gene. The TCRs are composed Hydroxychloroquine in vitro of either an αβ or a γδ pair of subunits. The structure of TCR is further stabilized by interchain disulphide bonds. At the 5′ end of each of the TCR loci there is a cluster of V segments followed by J segments (Fig. 1). In the TCR-β and TCR-δ chain loci, these segments are interrupted by a series of D segments similar to that of the immunoglobulin heavy chain (Fig. 1). Somatic recombination occurs in a strict regimen, with D to J recombination preceding V to DJ on the heavy chain and the heavy chain recombination in turn occurring before that of the light chains.[17] Similarly, the TCR-β rearrangement always precedes that of TCR-α. Besides, the TCR rearrangement is restricted

Immune system to early stages of the T-cell development and immunoglobulin rearrangement to early B cells. Adherence to this chronological order relies on the cell lineage and cell cycle restricted expression of participating enzymes as well as on chromosomal accessibility of the recombining loci.[18] A mature B lymphocyte expresses a single species of antibody possessing a unique specificity in spite of having multiple allelic loci for different antibody chains. This specificity is acquired by a process termed allelic exclusion.[19] Initially, two models were put forward to explain this process. In the case of the ‘regulated model’, gene assembly proceeds on one chromosome at a time and the protein products suppress further rearrangements by feedback inhibition.[20] The ‘stochastic model’ suggests that inefficient V(D)J rearrangement results in allelic exclusion.