A mysterious puzzle in immunology is how the immune system decides what types of immune response to initiate against various stimuli. Although much is known about control of T helper 1 (Th1) and Th17 responses, the mechanisms that initiate Th2 responses remain obscure. Antigen-presenting cells, particularly dendritic cells (DCs), are mandatory for the induction of a Th cell response. Numerous studies have documented the organizing role of DCs in this process. The present review summarizes the fundamental roles of DCs in inducing Th2 responses.
Allergy and Immunology ; Antigen-Presenting Cells ; Dendritic Cells* ; Immune System

DNA vaccination that can induce both cellular and humoral immune response has become an attractive immunization strategy against cancer and infectious disease. Elucidation of the precise mechanisms of immune priming will be important in the development of effective DNA vaccines. In this review, we illustrate possible mechanisms in priming cytotoxic T cell response involving the intracellular degradation, processing and presentation of encoded antigen. We also discuss the roles of costimulatory molecules expressed on antigen-presenting cells (APCs) in inducing optimal CTL activity. Hence, a rational strategy for increasing DNA potency would be to facilitate these pathways. Additionally, we focus on recent strategies including rapid degradation of ubiquitin-antigen fusion proteins, direct targeting to APCs for increased DNA uptake, direct routing an antigen into the MHC class I and II processing and presentation pathways, and increasing the immunogenicity of encoded antigen. All of these approaches have resulted in increased potency of DNA vaccines.
Animals ; Antigen Presentation ; Antigen-Presenting Cells ; immunology ; Lysosomes ; immunology ; Mice ; T-Lymphocytes, Cytotoxic ; immunology ; Ubiquitin ; physiology ; Vaccines, DNA ; genetics ; immunology

T cell can only recognize specific antigenic peptide-MHC complex on antigen-presenting cell. This is MHC restriction in antigen recognition of T cell. This phenomenon was discovered by an Austrian scientist Peter. C. Doherty and a Swedish scientist Rolf. M. Zinkernagel by chance. Then, in order to explain the phenomenon, they proposed two hypotheses: dual receptor and modified self. In the during following 20 years numbers of scientists spent great amount of time in the study of the phenomenon. The process of cell-mediated immune response becomes clear, which greatly promotes the advancing of immunology and many related disciplines.
Animals ; Antigen-Presenting Cells ; immunology ; Epitopes ; immunology ; Humans ; Immunity, Cellular ; Major Histocompatibility Complex ; immunology ; Receptors, Antigen, T-Cell ; immunology ; T-Lymphocytes ; immunology

As a member of the HSP90 family, heat shock protein (HSP) Gp96 is one of the most abundant proteins in the endoplasmic reticulum (ER), which displayed important molecular chaperones function in cells. Gp96 can stimulate the production of cytokines by activating the antigen presentation cells (such as dendritic cell, et al) in innate immunity. It is capable of eliciting an antigen-specific cytotoxic T lymphocyte (CTL) immune response to eliminate pathogens and tumors by facilitating antigen cross-presentation in adaptive immunity. Gp96 is also an ideal adjuvant in many recent researches. Here, we review the progress that addresses the role of biological characteristics, immunogenic mechanism that may be involved in the induction of anti-infection immune response and antitumor immunity, which may guide the new vaccine strategies with the knowledge of Gp96-antigen complexes.
Adjuvants, Immunologic ; genetics ; metabolism ; Antigen-Presenting Cells ; physiology ; Communicable Diseases ; immunology ; Dendritic Cells ; immunology ; Endoplasmic Reticulum ; immunology ; Humans ; Membrane Glycoproteins ; immunology ; Neoplasms ; immunology ; T-Lymphocytes, Cytotoxic ; immunology

Exosomes are nanometer sized membrane vesicles, released in the extracellular milieu following the fusion of the external membrane of multivesicular body (MVB) with plasma membrane. They perform a certain function in immune regulation. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin. Tumour-derived exosomes (TEX) exist in the supernatant of tumour cells, plasma and malignant effusions of tumour patients. They contain native candidate tumour associated antigen and are capable of transferring antigens to T lymphocytes, therefore efficiently promoting cytotoxic T lymphocyte (CTL) activation and producing antitumor immunity. However, recent evidence shows that tumor exosomes may induce immunologic tolerance and even activate immunosuppression which makes tumour escape from the immune surveillance of the host immune system. In addition, tumor exosomes may mediate a growth-promoting effect on tumor cells. These discrepancies are almost certainly due to differences in the phenotype of the exosomes.
Antigen-Presenting Cells ; immunology ; Antigens, Neoplasm ; immunology ; Cytoplasmic Vesicles ; immunology ; Endosomes ; immunology ; metabolism ; Exosomes ; immunology ; Humans ; Neoplasms ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Escape

OBJECTIVETo study the role of dendritic cells (DCs) and macrophages, differentiated from the same individual peripheral blood monocytes, in tumor antigen- presenting.

METHODSDCs and macrophages were differentiated from human peripheral blood monocytes by adding both Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) or GM-CSF only. Then they were loaded with tumor antigen at different concentrations and cocultured with autologous T cells in 96-well flat-bottomed microtiter plates for five days at 37 degrees C, 5% CO(2). (3)H-thymine was added before the culture terminated, and twelve hours later, the cells were gathered to test the cpm value.

RESULTSBoth DCs and macrophages chased with tumor antigen could strongly stimulate the proliferation of autologous T cells, especially DCs. The stimulation effect with 20 microl/ml antigen was the most remarkable and the cmp values were 11,950.3 +/-1621.8, 8,708.5 +/-176.1, 402.5+/-43.1 in DCs group, Macrophages group, and lymphocytes group, respectively.

CONCLUSIONThe antigen presenting role of DCs is stronger than that of macrophages from the same individual.

Antigen Presentation ; immunology ; Antigen-Presenting Cells ; immunology ; physiology ; Antigens, Neoplasm ; immunology ; Carcinoma, Hepatocellular ; immunology ; Dendritic Cells ; immunology ; physiology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Liver Neoplasms ; immunology ; Macrophages ; immunology ; physiology ; Tumor Cells, Cultured

OBJECTIVESTo explore the clinical and pathological features and the pathogenesis of primary biliary cirrhosis (PBC) in Chinese Mainland.

METHODS30 PBC patients were divided into the early group (Scheuer stage I and II, 19 patients) and the late group (Scheuer stage III and IV, 11 patients). The data of clinics and serology were analyzed, and the pathological features of the liver tissues were characterized. The changes of dendritic cells (DCs) and hepatic stellate cells (HSCs) were studied by immunohistochemistry.

RESULTSIn all the PBC patients, the rate of the male to the female was 1 to 5, and the average age was 40.6 years. The mean levels of TBiL, ALP and GGT in the sera were (95.9+-88.5) micromol/L, (537.2+-339.2) U/L, and (582.0+-351.2) U/L, respectively. 73.3% patients showed AMA positive, and the level of GGT was positively correlated with the AMA level according to the result of statistical analysis (r=0.778, P=0.000). The symptoms of jaundice and hepatomegaly were presented more commonly in the late group than those in the early group (chi2=5.182, P<0.05; chi2=13.659, P<0.01, respectively). The main changes of morphology of PBC located in portal tracts. The liver tissues in the early stage of PBC showed the damage of bile ducts and obvious proliferation of small bile ducts. The granulomas, the lymphoid follicles and the foamy cells were found in the liver tissues of PBC (2/19 patients, 12/19 patients, and 10/19 patients in the early stage respectively, while 0/11 patients, 4/11 patients, and 3/11 patients in the late stage respectively). There was significant difference between the early stage and the late stage in presence of the lymphoid follicles and the foamy cells (t=4.489, P<0.05; t=4.019, P<0.05, respectively). The biliary pigmentary particles were mainly accumulated in the liver cells around the portal tracts in 90.0% PBC patients, and the accumulation of copper and iron increased, compared with that in normal specimens. The DCs and HSCs located mainly in the portal tracts, especially around the damaged bile ducts.

CONCLUSIONSThere are some clinical and pathological characteristics in the patients with PBC. The level of AMA has no direct relationship with the level of transaminase or bilirubin. The proliferated bile ductules may express the antigens which maybe the target of immune attack. As an antigen-presenting cell, DCs may play an important role in the pathogenesis of PBC.

Adolescent ; Adult ; Antibodies, Antinuclear ; blood ; Antigen-Presenting Cells ; immunology ; pathology ; Dendritic Cells ; pathology ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; etiology ; immunology ; pathology ; Male ; Middle Aged ; Mitochondria ; immunology

It is necessary that the two signals are required in T cells activation. The first signal is specific, which T cell receptor could recognize and bind MHC molecule by antigen-presenting cells. Another one is nonspecific, which results from CD28/B7/CTLA4 molecules on T cells and antigen-presenting cells. The both of signals regulate function of T cells such as the activation, proliferation and secreting cytokines. CTLA4 showed the up-regulation in CD28/B7 costimulatory pathway as a negative signal. The immunosuppression could occur by blocking CD28/B7 pathway. It provided useful method for immunotherapy in the autoimmune diseases and graft-versus-host disease. But then, the activation of CD28/B7 could be valuable for the immune system recognizing and eliminating tumor cells.
Abatacept ; Animals ; Antigen-Presenting Cells ; immunology ; Antigens, CD ; Antigens, Differentiation ; immunology ; B7-1 Antigen ; immunology ; CD28 Antigens ; immunology ; CTLA-4 Antigen ; Humans ; Immunoconjugates ; Signal Transduction ; immunology ; T-Lymphocytes ; immunology

Recent technical approaches to investigating drug hypersensitivity have provided a great deal of information to solve the mechanisms that remain poorly understood. First, immunological investigations and in silico analysis have revealed that a novel interaction between T cells and antigen-presenting cells, namely the pharmacological interaction concept, is involved in drug recognition and the hapten theory. Second, progress in immunology has provided a new concept of CD4+ T cell subsets. Th17 cells have proven to be a critical player in acute generalized exanthematous pustulosis. Our recent findings suggest that this subset might contribute to the pathogenesis of Stevens-Johnson syndrome/toxic epidermal necrolysis. Third, alarmins, molecules associated with innate immunity, are also associated with exaggeration and the persistence of severe drug hypersensitivity. The latest innovative techniques are providing a new landscape to examine drug hypersensitivity.
Acute Generalized Exanthematous Pustulosis ; Alarmins ; Allergy and Immunology ; Antigen-Presenting Cells ; Computer Simulation ; Drug Hypersensitivity ; Hypersensitivity ; Immunity, Innate ; Receptors, Antigen, T-Cell ; T-Lymphocyte Subsets ; T-Lymphocytes ; Th17 Cells

In order to investigate the cellular immunoresponses mediated by chimeric anti-CD20 monoclonal antibody (anti-CD20 McAb) through dendritic cells (DCs), mononuclear cells were isolated from human peripheral blood (PBMNC) and DCs from PBMNCs in vitro were generated with normal methods. Human CD20 positive lymphoma cell line-Raji cells were treated with different methods including treatment with anti-CD20 McAb (group R), treatment with heat-induced apoptosis (group A) and treatment with anti-CD20 McAb+heat-induced apoptosis (group R+A), then Raji cells treated with above-mentioned methods as tumor antigen were loaded on DCs. The phagocytosis of DCs to tumor antigen was observed by transmission electron microscope (TEM), the auto-mixed lymphocyte reaction was performed with antigen-primed DCs, the release of INF-gammafrom effector cells was detected by ELISPOT, the killing of effector cells on Raji cells was assayed by MTT. The results showed that under TEM, no pronounced phagocytosis of DCs was seen in group R, while the phagocytosis of apoptotic bodies could be easily seen in group A and the more cell fraqments were observed in group R+A. The FCM indicated that the expressions of CD80, CD86 and HLA-DR on DCs in 3 experimental groups were higher than those in group control (p<0.05), while expression positive rate in group R+A was higher than those in group R and A (p<0.05). The detection of lymphocyte surface antigen revealed that proportions of CD8+ cells in all experimental groups were higher than those in group control (p<0.05), count of CD56+ cells in group R and R+A increased, as compared with group A and control, difference was significant (p<0.05). ELISPOT assay indicated that amount of cells releasing IFN-gamma in all experimental groups was higher than that in group control, and also number of spots in group R+A significantly higher than that in other groups at effector-targetor ratio=1:10 (p<0.05). The results of killing assay demonstrated that killing rate on Raji cells in all experimental groups increased as compared with group control (p<0.05), while killing rate in group R+A was higher than that in group R and A. It is concluded that anti-CD20 McAb can mediate DC to induce cellular immunoresponse against lymphoma, that is, to stimulate and amplify specific CTLs and NK cells. Anti-CD20 McAb combined with DCs primed by heat-stressed tumor cells as antigen can further enhance cellular immunoresponse against lymphoma.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antigen Presentation ; Antigen-Presenting Cells ; immunology ; Antigens, CD20 ; immunology ; Chimera ; Dendritic Cells ; immunology ; Humans ; Hyperthermia, Induced ; Lymphoma, B-Cell ; immunology ; Mice ; T-Lymphocytes, Cytotoxic ; immunology