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Leukocytes and lymphoid tissues: The framework of the immune system
Published in Gabriel Virella, Medical Immunology, 2019
The end result of this process is an increase in leukocyte migration to specific areas where those cells are needed to eliminate some type of noxious stimulus or to initiate an immune response. Some of the lymphocytes that migrate to a tissue where they can be stimulated by a specific antigen will differentiate in tissue resident memory T cells (TRM), a different subpopulation than the central memory T cells (TCM), which remain in circulation and are attracted to endothelial cells expressing inflammatory cytokines. Both subpopulations will contribute to inducing a potent and rapid immune response to the specific antigens that they have previously recognized.
Vaccine Development Strategies and the Current Status of COVID-19 Vaccines
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Mohsen Akbarian, Kenneth Lundstrom, Elrashdy M. Redwan, Vladimir N. Uversky
While SARS-CoV-2 is considered a mucosal-borne virus (oral-nasal cavities), so far all approved vaccines against it have been delivered by intramuscular injection. However, both adenovirus- and influenza virus-based vaccine candidates, are under development for intranasal administration. As previously summarized [28], there are two main types of mucosal surfaces: (1) Stratified columnar epithelial surfaces (examples include lung, gut, and endocervix); and (2) Stratified squamous epithelial surfaces (found, for example, in the nose, eyes, vagina, and ectocervix). Both types of these epithelial layers use differential adaptive immune mechanisms for protection, which means that the vaccine must stimulate type-appropriate effector responses [28]. Notably, polymeric immunoglobulin receptors (pIgRs) are expressed on the former type of epithelial surfaces, and can transport dimeric IgA to the lumen, suggesting that they can neutralize incoming pathogens or toxins. On the contrary, however, the latter type of epithelial surface lacks pIgRs and relies on IgG for protection. In the upper respiratory tract, IgA protects the nasal cavity, whereas IgG protects the lower respiratory tract (lung). Both types of mucosal surfaces can host tissue-resident memory T cells. Mucosal immunity provides opportunities to block infection. Promising results were obtained in experimental animal models after immunization with the SARS-CoV vaccine candidates based on the RBD of SARS-CoV S protein, which elicited mucosal immunity, playing a central role in protection during virus challenge [29]. However, little or no information is currently available on the protective mucosal immunity stimulation by COVID-19 vaccines in humans.
Immunology of Skin and Reactivity
Published in Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters, Cosmetic Formulation, 2019
Krishna Telaprolu, Heather A.E. Benson, Jeffrey E. Grice, Michael S. Roberts, Philip L. Tong
T cells have long been known to form the adaptive arm of the skin immune system, although more recently new classes of T cells have demonstrated more innate functions. Circulating T cells and resident T cells protect the host from de novo infection (Boyman et al., 2007). The resident T cells hold a strategic position near the LCs for rapid protection of skin from pathogen infection (Schenkel and Masopust, 2014). The dermis predominantly contains CD4+ memory T cells and some CD8+ cells located near the dermal–epidermal junction, while the epidermis contains CD8+ αβ memory T cells that reside for extended periods in the epidermis and are commonly referred to as tissue-resident memory T cells (Trem) (Gebhardt et al., 2009; Mueller et al., 2014). The Trem cells express a unique set of markers, including CD69 (expressed in skin T cells independent of antigen recognition), VLA-1 and CD103 (Gebhardt et al., 2009). These T cells enter the dermis from blood and are recruited into the epidermis during inflammation by the expression of the CXCR3 ligand of chemokine receptors (Mackay et al., 2013). The skin also consists of 5% of regulatory T cells (Treg), which actively circulate between lymph nodes and skin, and regulate the T cell responses, some functions of APCs such as DCs and macrophages, and neutrophil accumulation during early stages of inflammation. Treg induce the anti-inflammatory functional profile in macrophages by inhibiting the production of TNF-α and have immunosuppressive activity related to cancer. The skin also contains γδ T cells, which are responsible for cutaneous immunosurveillance against pathogens, wound healing and contact hypersensitivity (Macleod and Havran, 2011; Sumaria et al., 2011). Recently γδ T cells were shown to be major producers of IL17, which is now a novel target in the management of psoriasis (Langley et al., 2014; Cai et al., 2011).
Diversity of T cells in the skin: Novel insights
Published in International Reviews of Immunology, 2023
Natalija Novak, Leticia Tordesillas, Beatriz Cabanillas
Depending on their functionality and their location, memory T cells can be classified into different subsets, such as central memory T cells (TCM), effector memory T cells (TEM), and tissue-resident memory T cells (TRM) (Figure 2). TCM and TEM have recirculating capacity and are denominated recirculating memory T cells, while TRM are parked in tissues such as skin and do not possess the capacity to recirculate. TEM express skin-homing addressins and are characterized by effector functions such as production of high levels of effector cytokines [3]. TEM are differentiated cells that are rapidly induced in tissue areas outside of LNs and they lack the capacity to generate secondary expansions [12]. On the other hand, TCM that have an intermediated differentiation stage, monitor LNs and proliferate upon encounter with pathogenic antigens in the secondary lymphoid organs (SLOs) [12,13]. TCM express central memory markers such as CCR7 and CD62L (L-selectin) and it has been found that they can also express skin-homing markers like CLA and CCR4 that allow them to recirculate between LNs, blood, and skin [14,15]. In that sense, it has been shown that TCM are one of the first memory T cells that infiltrate the skin upon infection produced by certain microorganisms such as vaccinia virus and it has also been shown that TCM can give rise to some TRM such as CD69+ TRM [16,17].
The landscape of systemic therapy for early stage triple-negative breast cancer
Published in Expert Opinion on Pharmacotherapy, 2022
Jin-Yu Lu, Alvaro Alvarez Soto, Jesus D Anampa
Over the past several years, the arrival of ICIs and targeted therapy has been transforming the treatment landscape of TNBC. However, ICIs can be associated with irAEs and financial toxicities. Therefore, we need to identify biomarkers that can optimally select patients who would benefit from the addition of ICIs to chemotherapy including novel assays for PDL1 expression, tumor infiltrating lymphocytes, tumor mutation burden, and immune gene expression profiles. While the GeparNuevo, NeoTRIP, and other trials on ICIs showed only a modest increase of pCR rate, ICIs have significantly improved the long-term survival in the KEYNOTE-522 [49,50] and GeparNuevo [47]. The discordance suggests that pCR may not be the right end point for ICI trials, and future trials need to be designed based on survival end points. Unlike conventional cytotoxic drugs, ICIs activate immune cells to mount an often delayed but persistent anticancer immune response. Tissue-resident memory T cells, a subset of tumor-infiltrating lymphocytes (TILs), are associated with improved PFS and OS in patients with early stage TNBC [73], suggesting a crucial role in breast cancer control [74]. Further investigations on the immune microenvironment, including tissue-resident memory T cells, are warranted and could realize the full potential of immunotherapy.
Genetic markers of drug hypersensitivity in pediatrics: current state and promise
Published in Expert Review of Clinical Pharmacology, 2022
Abdelbaset A. Elzagallaai, Michael J. Rieder
Other factors that have been found to contribute to the development of DHRs is concomitant infections especially viral [69]. It is not well known whether viral activation a consequence or a cause of the hypersensitivity reactions, however, one possible explanation is that stressed infected cells may release ‘danger signals’ required for maturation and priming of immune cells to mount the reactions [70,71]. The proposed role of tissue resident memory T-cells in protection against viral infection and the collateral tissue damage resulting in immune activation is appealing although direct evidence is still lacking [72].