China
Africa
Explore chapters and articles related to this topic
Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
T cell phenotype: Activated T and B cells in the lymph node downregulate CCR7, begin to express receptors for chemokines that are preferentially expressed in the peripheral tissue and migrate to the site of pathogen entry. CD4 T cells (also called Th0) differentiate into T helper 1 cells (Th1), T helper 2 cells (Th2), and T helper 17 (Th17) cells, whereas CD8 T cells differentiate into cytotoxic T cells (Tables 1.3 and 1.4). Under specific circumstances cytotoxic CD8 T cells can differentiate into Tc1 and Tc2 cells, whose cytokine production profile is similar to that Th1 and Th2 cells. The differentiation of Th1, Th2 and Th17 cells is induced by IL-12, IL-4, and IL6, IL1 (in humans) and TGFb (in mice) respectively (Glimcher 2001). The foregoing cytokines are typically secreted by the antigen-presenting cell and/or other accessory cells. For Th1 differentiation IL-12 signaling via STAT-4 is essential, which activates the master Th1 regulator—T-bet, a transcription factor that induces sustained production of Th1 cytokines and also blocks Th2 differentiation. IL-4 signaling via STAT-6 and other signaling molecules, induces the master Th2 switch—GATA-3. GATA-3 stimulates Th2 cytokine production and inhibits Th1 differentiation (Table 1.4). IL6 stimulated STAT3 in the presence of TGFb induces RORgT, the master regulator of Th17. Th1 cells are primarily induced by and play a critical role in the defense against intracellular pathogens. Th2 cells are induced by extracellular pathogens/antigens. Th17 cells are induced by pathogens but are involved in autoimmunity in addition to defense against pathogens.
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
The pathophysiology of MS involves myelin-reactive CD4+ T cells, imbalanced CD8+ T cells, inflammatory B cells, altered NK function, production of autoantibodies, genetic predisposition, and nongenetic factors [45]. The main etiology is the violation of immunological tolerance and an active penetration of immune cells sensitized to myelin antigens through the blood–brain barrier (BBB) into the brain tissue. There is a critical pathogenic role of the Th1- and Th17-cells that respectively produce the pro-inflammatory cytokines IFN-γ and IL-17 [46]. There are also data showing that NK and B cells serve as players in the disease. For example, immune-modulating therapies targeting NK cells in MS have suggested a regulatory role for these cells on CD4+ T cell proliferation and activity, which are dysregulated during disease progression. A single administration of rituximab (an anti-CD20 monoclonal antibody that depletes B cells) have been shown to reduce brain lesions and clinical relapses for 48 weeks. Hence, B cell subsets appear to play antibody-dependent or -independent pathogenic functions in MS.
Immune Testing in Recurrent Pregnancy Loss*
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
Jeffrey Braverman, Darren Ritsick, Nadera Mansouri-Attia
A shift toward Th2 dominance is characteristic of early pregnancy, and the paradigm that the Th1/Th2 balance of early pregnancy regulates the nature of the alloimmune response to the conceptus has been prominent in the field of clinical reproductive immunology. In recent years, there has been an increasing recognition that the Th1/Th2 paradigm of the immunological response to pregnancy is insufficient and the importance of Treg cell responses has become more prominent [40,41]. Concurrently, the opposing roles of Treg cells and Th17 cells in many conditions, including autoimmunity and transplant tolerance, have become increasingly recognized. Indeed, our data indicate that the strongest prognostic factors in early pregnancy for a successful outcome (live birth after an uncomplicated pregnancy) are efficient Treg cell recruitment from the peripheral blood to the decidua (as measured by the percent decrease of Treg cells in the peripheral blood) and a lack of a significant increase in levels of IL-17 producing cells, including Th17 cells, IL-17 positive CD8+ T cells (Tc17 cells), IL-17 positive NKT cells (NKT17 cells), and IL-17 positive NK cells (NK17 cells).
Host-directed antileishmanial interventions: Harvesting unripe fruits to reach fruition
Published in International Reviews of Immunology, 2023
With a well-defined Th1/Th2 dichotomy that has opposing effects on host immune response, CD4+ T cells are the ultimate orchestrators of adaptive immune response during Leishmania infection. The view that CD4+ T cells differentiate into Th1 or Th2 cells has categorically expanded over the last two decades, with recent inclusions of other subsets found to have a profound role in disease susceptibility. One of them includes Th17 cells that produce strong pro-inflammatory responses via recruitment of neutrophils to the site of infection and production of IL-17. Several vaccination studies hint at the protective role of these cells. Administration of live L. major parasite with CpG DNA vaccine promotes proliferation of Th17 cells, leading to reduced lesions and conferring long-term resistance [118]. In experimental VL, similar observations have been made. Adoptive transfer of bone marrow derived dendritic cells (BMDCs) stimulated with CpG correlated with increased levels of IL-17 during L. infantum challenge [119].
New insights into the metabolism of Th17 cells
Published in Immunological Medicine, 2023
The vital role of Th17 cells in the pathogenesis of autoimmune diseases is well-established. Experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, or a colitis model have been used to examine the pathogenesis of Th17 cells in vivo. Furthermore, Th17 cells are found in the skin lesions of psoriasis and mediate skin inflammation in mice and humans [18]. In the synovial fluid of patients with rheumatoid arthritis, high concentration of IL-17 are present, which enhance osteoclastogenesis [19]. Th17 cells promote the release of IL-6 and matrix metalloproteinases (MMPs) from synovial fibroblasts [20]. In patients with systemic lupus erythematosus (SLE), an increased number of Th17 cells or serum IL-17 levels have been demonstrated [21–23]. Higher serum IL-17 levels are associated with lupus nephritis class IV and V and correlate with lupus disease activity [24,25]. In patients with systemic sclerosis, a high frequency of Th17 cells and high levels of serum IL-17A are also reported [26,27]. Th17 cells are partially involved in the pathogenesis of other autoimmune diseases, including large vessel vasculitis, ANCA-associated vasculitis, Behcet’s disease and graft versus host disease (GvHD) [3,28–30]. Since the therapies targeting IL-17 in lupus nephritis, Takayasu arteritis, systemic sclerosis and other autoimmune diseases are now ongoing clinical trials (Table 4), the results are awaited.
Stress Suppresses Systemic Th17/Treg Imbalance in Rats with Experimental Autoimmune Uveitis
Published in Ocular Immunology and Inflammation, 2022
Jike Song, Dadong Guo, Qingmei Tian, Qiuxin Wu, Xiuyan Zhang, Hongsheng Bi
Experimental autoimmune uveoretinitis (EAU) induced by interphotoreceptor retinoid-binding protein (IRBP) in either mice or rat is an animal model that resembles human uveitis clinically and histopathologically in many aspects, providing an important method for studying the pathogenesis of as well as treatment strategies for human uveitis.28,29 The immunopathological process of EAU is composed of two consecutive stages: the immune activation phase and the immune effector phase.30 During the first stage, lymphocytes are activated in the peripheral lymphoid organs, and during the second stage, these autoreactive T cells infiltrate the eye and perform effector functions, resulting in autoimmune injury of the eye.30,31 It is widely acknowledged that self-reactive T cells and proinflammatory cytokines play a key role in the induction, progression, and recurrence of EAU.32–34 Helper T cells 17 (Th17) and CD4+CD25+ regulatory T cells (Treg) are important subsets of CD4+ T cells. Th17 and Treg cells are derived from naïve T cells, and Th17 cells mediate the inflammatory reaction, whereas Treg cells mediate immune tolerance.35–38 There is antagonism in the function and differentiation between Th17 and Treg cells. Thus, the balance of Treg and Th17 cells is crucial for the maintenance of the immune status.