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Immune Testing in Recurrent Pregnancy Loss*
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
Jeffrey Braverman, Darren Ritsick, Nadera Mansouri-Attia
As discussed above, SAB testing can be used to detect humoral responses to specific paternal HLA antigens. Reliable assays for the detection of antigen-specific cellular (T cell-mediated) responses have also been developed and have been applied in the setting of transplantation. However, these assays detect allorecognition through direct antigen presentation which is not relevant to pregnancy. Although more technically difficult, similar assays to detect allorecognition through indirect antigen presentation are also being developed. The ability to sensitively and reliably detect both cellular and humoral responses specifically to paternally-derived antigens will significantly advance the field of clinical reproductive immunology.
The Major Histocompatibility Complex
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
The TCRs of alloreactive cells were selected in the thymus (as were those of all T cells) to recognize self MHC plus foreign peptides. Many of these TCRs may also interact with a combination of foreign MHC and peptide. It is still not yet clear exactly what is (are) the antigenic determinant(s) which bind the TCRs of responding alloreactive cells, but the high frequency of alloreactive cells reflects the multitude of cross-reactions of this type. This concept is supported by the tremendous diversity in TCR α and β genes expressed in alloresponsive cells. In addition, some of these TCRs may bind to a single allo-MHC molecule when complexed with many different peptides. This may be because the allo-MHC alone mimics the actual specificity of the TCR, the complexed peptide simply serves to hold it in the appropriate conformation. In these cases, specificity correlates with sequential residues in an exposed region of the MHC. Alternatively, the allo-MHC may also be presenting a peptide fragment of itself. Presentation of allo-MHC peptides by self MHC also occurs. Whether or not peptide is important (apart from simply holding MHC molecules in appropriate conformation) in all instances of allorecognition is not clear. It may be that a low-affinity interaction between TCRs and the large amounts of allo-MHC on the cell surface is sufficient to activate many clones irrespectively of the peptides bound by allo-MHC.
Adaptive immune response: Antigens, lymphocytes, and accessory cells
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, John W. Sleasman
Cytotoxic T lymphocytes also differentiate and proliferate when exposed to cells from an individual of the same species but from a different genetic background. In vitro, the degree of allostimulation between cells of two different individuals can be assessed by the mixed leukocyte reaction. Two recognition pathways have been proposed (Figure 4.7): Direct allorecognition of non-self MHC molecules by lymphocytes expressing alloreactive T-cell receptors.Indirect recognition of allogeneic peptides (probably resulting from ingestion and processing of dead donor cells or proteins) associated with MHC-II molecules by Th1 cells expressing receptors for non-self peptides.
Applications of Transcriptomics in the Research of Antibody-Mediated Rejection in Kidney Transplantation: Progress and Perspectives
Published in Organogenesis, 2022
The allograft rejection starts from the recognition of alloantigens by recipient T cells. Allorecognition can be divided into direct, indirect, and semi-direct types.5 In direct allorecognition, the recipient T cells recognize the alloantigens presented by donor antigen-presenting cells (APCs). In indirect allorecognition, the alloantigens are processed into peptides by the recipient APCs and presented to the recipient T cells. The activated CD4 T cells help activate CD8 T cells to differentiate into cytotoxic effectors.6 In semi-direct allorecognition, recipient APCs acquire donor anti-human leukocyte antigen (HLA) molecules that present peptides directly to recipient T cells.7 In indirect allorecognition, T cells differentiate into T follicular helper T (Tfh) cells.8 The interaction between Tfh cells and B cells requires the signals of co-stimulatory and co-inhibitory molecules, and cytokines.9
Lessons from transmissible cancers for immunotherapy and transplant
Published in Immunological Medicine, 2022
Rafael Cardoso Maciel Costa Silva, Carolina Panis, Bruno Ricardo Barreto Pires
Tumor transplantation studies paved the way for an increased understanding of major histocompatibility complex (MHC) biology [1]. At that time, the mechanisms that governed tissue rejection (and, in this case, cancer rejection as well) were not established. Currently, many advances have allowed us to better comprehend these mechanisms, many of which are also significant barriers to a possible cancer transmission through allogeneic responses. The immune response against foreign cells that express different MHCs repertoires (allorecognition) is the main driver of tissue rejection [2]. The MHC codes for critical polygenic and polymorphic molecules (evaluated before transplant donor selection) involved with antigen presentation to T cells. MHC type I molecules (MHC-I), usually expressed by all nucleated cells within vertebrates, interact with T cell receptors (TCRs) from CD8+ T cells, mainly responsible for cytotoxic adaptive immune responses. MHC type II (MHC-II), expressed mainly by professional antigen presenting cells, such as dendritic cells (DCs) and activated macrophages, interact with TCRs from CD4+ T cells that are responsible for ‘helper’ adaptive immune responses, ‘orchestrating’ different aspects of cellular and humoral immunity. Foreign MHCs are very important to tissue rejection and, as discussed in this review, transmissible cancer immune response.
Design and Optimization of PLGA Particles to Deliver Immunomodulatory Drugs for the Prevention of Skin Allograft Rejection
Published in Immunological Investigations, 2020
Khawar Ali Shahzad, Muhammad Naeem, Lei Zhang, Xin Wan, Shilong Song, Weiya Pei, Chen Zhao, Xiaoxiao Jin, Chuanlai Shen
The size of the biomimetic particles is an important parameter in the design of drug delivery system as particles are anticipated to interact with biological systems at nano- and microscale. The size difference can affect the nature of the particle, its applications, and outcomes of treatment therapy. Blood particle interaction, slurry viscosity, patient conditions and particle aggregations are key problems (Cleland et al. 1993; Giteau et al. 2008; Van De Weert et al. 2000). Cell-sized particles (4–5 µm) are suggested for cellular mimicry by various researchers for potent effect on the target cells as they are found more effective in modulating T cell response (Balmert and Little 2012; Mescher 1992). On the other hand, the large size of microparticles can result in lodging of the vasculature (as they can embolize the vessels of the same diameter which can result in blockage in blood flow), synchronized drug delivery and production of hepatocellular carcinomas (Gratton et al. 2008; Harris et al. 2001). In case of alloskin transplantation therapy, 4–5 µm cell-sized PLGA Killer Artificial Antigen Presenting Cells (KaAPCs) are documented with the issue of not reaching to the allograft through vascular circulation (Champion et al. 2008; Kohane 2007). Therefore, the depletion of alloreactive T cells was carried out in direct pathway of allorecognition. However, cell-sized particles presented the reduced risk of engulfment by phagocytes (Wang et al. 2017).