Anti-infectious innate and adaptive immune responses
Gabriel Virella in Medical Immunology, 2019
This T-cell subpopulation is predominantly localized to epithelia and appears to recognize and eliminate infected epithelial cells. In humans, there are two major subsets of γ/δ T cells identified by their γ/δ chain. γ/δ1 T cells are predominant in the thymus and epithelial tissues and recognize various stress-related antigens. γ/δ2 T cells constitute the majority of blood γ/δ T cells. Both subsets share a common Vγ9 chain. Human Vγ9/Vδ2+ T cells can be activated by microbial products (e.g., phosphorylated metabolites) as well as by markers of cellular stress released by infected or transformed cells. The activation of γ/δ T cells can be mediated by their T-cell receptors (TCRs) assisted by costimulatory signals from natural killer (NK)-type receptors but do not involve major histocompatibility complex (MHC)–associated presentation of the activating compounds. The γ/δ TCRs also recognize lipid antigens presented by CD1 molecules, in particular CD1d. Once activated, γ/δ T cells show a great degree of plasticity. They can release proinflammatory cytokines, cause cytolysis of infected or transformed cells by the same mechanisms as classical cytotoxic CD8 T cells, and become professional antigen-presenting cells. Thus, γ/δ T cells appear to be one of the bridges between innate and adaptive immunity.
Internalization of Lipopolysaccharide by Phagocytes
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
One plausible hypothesis is that partial deacylation prepares LPS for presentation as an antigen. Interesting recent evidence suggests that other lipoglycan molecules may be presented, bound to one or more isoforms of CD1, on the surfaces of antigen-presenting cells. CD1 has a deep hydrophobic groove (82) into which the lipid moiety of lipoarabinomannan, mycolic acid, and other lipoglycans may insert (83). Internalized ligand and CD1 evidently meet in multi vesicular bodies (MIIC), where CD1 undergoes an acid-dependent conformational change that allows insertion of the lipid moiety of the ligand into its hydrophobic groove (84). The ligand-CDl complex then moves to the cell surface, where it can be recognized by specific T cells. Partial deacylation of the lipid moiety of LPS might be required to trim the bulky, rigid lipid A structure to a size that would fit into the presentation groove of CD1 or another protein.
Host Defense and Parasite Evasion
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2015
NK cells are not the only lymphocytes that appear to mediate an initial innate response to Plasmodium .Unlike other T cells we have discussed, invariant natural killer T cells (iNKT cells) bear neither CD4 nor CD8. Consequently, they do not recognize antigen presented by MHC. They have T-cell receptors (TCRs) with extremely limited diversity, and unlike TCRs on conventional T cells, which recognize only peptides, iNKT receptors seem to recognize glycolipids. Glycolipids are presented to iNKT cells by a molecule called CD1, which is similar to MHC in its ability to present certain antigens. The main response of iNKT cells seems to be the very rapid secretion of certain cytokines, including IL-4. Consequently, they are able to promote a Th-2 response. They also seem to activate another type of unusual lymphocyte called a B1 B cell. These cells are quite distinct from the conventional B cells we have discussed so far. B1 B cells have very limited receptor diversity and seem to make antibody primarily against polysaccharide antigens without the assistance of CD4+ T cells. Because they do not require Th cells to become activated, B1 B cells can secrete antibody within 48 hours of an infection—well before the time required by conventional B cells to proliferate and differentiate into plasma cells. The antibody secreted by B1 B cells is primarily of the IgM class. There is no B1 B-cell memory response and the amount of antibody and the speed with which it is produced does not increase with subsequent exposure. Nevertheless, the antibody they produce may represent an important rapid and specific humoral response to Plasmodium that is independent of MHC.
Dendritic Cells Currently under the Spotlight; Classification and Subset Based upon New Markers
Published in Immunological Investigations, 2021
Samaneh Soltani, Mahdi Mahmoudi, Elham Farhadi
In humans, the CD1 family have been classified into two groups. Group 1 consists of CD1a, CD1b, and CD1 c, which are expressed on APCs, are able to present various forms of self and microbial lipid antigens to CD4 and CD8 positive, as well as double-negative T cells. In contrast, group 2 consists only of CD1d isoform, which presents an unusual glycosphingolipid (a-galactosylceramide) to NKT cells (Kaczmarek et al. 2017). CD1a is used as a marker of CD34+ derived DCs but has been identified to be expressed on the surface of the dermal DCs and LCs (Fehres et al. 2015). Although both of LCs and CD1a DC cells express CD1a, the LCs are Langerin+, and the CD1a+ DCs are Langerin- (Cernadas et al. 2009). Both of CD1a high and CD1a low dermal DCs express CD4 and macrophage mannose receptor (MMR), but the latter is DC-SIGN positive. Furthermore, CD1a high and CD1a low dermal DCs are gp120 binding positive and therefore are able to bind HIV (Turville et al. 2002). CD101 is one of the surface markers on this subset that is capable of modulating T-cell responses through IL-10 secretion (Clark et al. 2019).
Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence
Published in Expert Review of Vaccines, 2022
Maryam Abbaspour, Vajihe Akbari
In a phase I clinical study DCs pulsed with HER2 peptides were evaluated in subjects with HER2-positive ductal carcinoma in situ (DCIS). Autologous DCs were activated in vitro with IFN-γ and a TLR agonist, bacterial lipopolysaccharide to assure generation of highly polarized DC1 cells that secrete high levels of IL-12p70. CD1 cells were loaded with HER2 MHC class II epitope. For HLA-A2-positive patients, CD1 cells were further pulsed with HER2 MHC class I epitopes. The vaccine was administered directly into lymph nodes of BC patients before surgical resection. The results showed that vaccinated patients developed antigen-specific immunity and showed high levels of HER2-specific CD4+ Th and CD8+ CTL cells. In addition, HER2-pulsed DC vaccines led to accumulation of lymphocytes in the breast and induction of antibody-dependent cell-mediated cytotoxicity. Most patients also exhibited significantly decreased expression of HER2 in surgical tumor specimens. Therefore, DC1 vaccination strategies may be useful for both the prevention and treatment of early BC [47].
Murine models of psoriasis and their usefulness for drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Shih-Yi Chuang, Chih-Hung Lin, Calvin T. Sung, Jia-You Fang
Both psoriasis and cardiovascular disease correlate with hyperlipidemia. Recent studies have identified CD1-restricted self-lipid-reactive T cells in human blood and skin [57,58]. Bagchi et al. [59] developed a new mouse model for the study of human CD1-restricted T cell response to self-lipids in vivo. Surprisingly, the hCD1Tg HJ1Tg Apoe–/– mouse spontaneously develops psoriasiform skin inflammation characterized by epidermal hyperplasia, hyperkeratosis, T cell and neutrophil infiltration, and a Th17-dependent cytokine response. S100a7 and S100a8 mRNA levels are higher in the diseased hCD1Tg HJ1Tg Apoe–/ – mouse. No significant difference in the percentages of B cells, macrophages, or DCs has been detected.
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