scholarly journals HLA Expression at the Maternal-Fetal Interface

1998 ◽  
Vol 6 (3-4) ◽  
pp. 197-204 ◽  
Author(s):  
Heinz Hutter ◽  
Astrid Hammer ◽  
Gottfried Dohr ◽  
Joan S. Hunt
Keyword(s):  
Immune System ◽  
Hla Class I ◽  
Short Review ◽  
Maternal Blood ◽  
Protective Mechanisms ◽  
Hla Class I Molecules ◽  
Recent Developments ◽  
The Subject ◽  
Class Ii Antigens ◽  
Maternal Fetal Interface

Pregancy in the human presents an “immunological paradox,” because of the unexpected willingness of mothers to accept genetically disparate tissues. The fact that the fetus can develop unharmed for nine months shows that protective mechanisms must exist to permit its survival. The conditions that permit the genetically dissimilar human fetus to evade rejection by its mother's immune system have been the subject of intense interest for several decades. As the placental cells, which are in contact with maternal blood or tissue, are devoid of HLA class II antigens, interest has focused on the expression of HLA class molecules. Recent developments in the constitutive, transcriptional, and translational expression of HLA class I molecules on anatomically and morphologically different subpopulations of trophoblast cells will form the basis of this short review.

scholarly journals Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

2020 ◽  
Vol 21 (13) ◽  
pp. 4756
Author(s):  
Chiara Tersigni ◽  
Federica Meli ◽  
Caterina Neri ◽  
Azzurra Iacoangeli ◽  
Rita Franco ◽  
...  
Keyword(s):  
Immune System ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Immune Recognition ◽  
Protective Mechanisms ◽  
Maternal Immune System ◽  
Hla Class I Molecules ◽  
Classical Pattern ◽  
Hla Molecules

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman’s immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal–fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.

HLA class I molecules in implantation

2001 ◽  
Vol 12 (4) ◽  
pp. 299-314
Author(s):  
YW Loke ◽  
Ashley King
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Research Effort ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Antigens ◽  
Transplantation Immunology ◽  
Hla Class I Molecules ◽  
Unusual Combination ◽  
Clinical Transplantation

Because half its genes are inherited from the father, the embryo during pregnancy has been frequently compared to an allograft transplanted into the maternal uterus. The question why the embryo is, therefore, not rejected by the mother's immune response in the same way as other allografts has still not been satisfactorily answered. Recent investigations indicate that this analogy may not be as close as it initially appears. One major difference is the expression of an unusual combination of HLA class I molecules by the placental trophoblast cells which invade into uterine decidua during implantation. Furthermore, the lymphoid population in the uterus potentially capable of interacting with these trophoblast HLA class I antigens also appears to be unique. These observations have led to the suggestion that implantation might utilise a novel immune system which is different to that seen in clinical transplantation immunology. Much research effort is now directed towards the elucidation of the mechanisms involved and the outcome of this interaction because this is likely to be how implantation is controlled.

scholarly journals Current trends in oxysterol research

2016 ◽  
Vol 44 (2) ◽  
pp. 652-658 ◽  
Author(s):  
William J. Griffiths ◽  
Jonas Abdel-Khalik ◽  
Thomas Hearn ◽  
Eylan Yutuc ◽  
Alwena H. Morgan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Viral Infection ◽  
Th17 Cell ◽  
Neuronal Development ◽  
Short Review ◽  
Current Interest ◽  
Current Trends ◽  
Recent Developments

In this short review we provide a synopsis of recent developments in oxysterol research highlighting topics of current interest to the community. These include the involvement of oxysterols in neuronal development and survival, their participation in the immune system, particularly with respect to bacterial and viral infection and to Th17-cell development, and the role of oxysterols in breast cancer. We also discuss the value of oxysterol analysis in the diagnosis of disease.

Blocking LILRB and KIR receptors by B57 open conformers induces potent antitumor activity and acts synergistically with checkpoint blockade inhibition.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14137-e14137
Author(s):  
Christoph Renner ◽  
Michael A. Curran ◽  
Julia Kolibaba ◽  
Yang Liu ◽  
Ulf Petrausch ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune System ◽  
Mouse Models ◽  
Macrophage Polarization ◽  
Hla Class I ◽  
Dimensional Structure ◽  
Ligand Interaction ◽  
Hla Class I Molecules ◽  
Kir Receptors ◽  
Anti Tumor Activity

e14137 Background: HLA open conformers (OC) are defined as HLA class I molecules lacking beta-2-microglobulin (β2m) and peptide. OC can be derived from different HLA I molecules such as HLA-B27, -B57, and –Cw08. OC have a different three dimensional structure when compared to their respective HLA/β2m/peptide counterpart and induce distinct immunological processes by binding to LILRB and KIR molecules, both key receptors of the innate immune system. B57 OC expression is associated with enhanced immunity against viruses and can cause autoimmunity. Its potential anti-tumor activity has not been exploited so far. Methods: B57 OC and control molecules were expressed as IgG4 fusion proteins in CHO cells. The affinity for protein-ligand interaction was measured by surface plasmon resonance (SPR). Human macrophages M1/M2, phagocytosis and NK cytotoxicity were assessed by flow cytometry and cellular assays. Syngeneic pancreatic cancer (Pan02) or colon cancer (MC38) mouse models were used. Mice with tumors of 80mm3were treated twice weekly at 5 mg/kg. Tumor and blood samples were analysed. FDA cancer panels were assessed by IHC for LILRB1-5 expression. Results: B57 OC displays distinct protein-ligand interactions with high affinity binding to LILRB2 & 4, KIR2L1-3, and KIR3DL1. Therapeutic efficacy in pancreatic and colon cancer models was observed with monotherapy (p < 0.01), and combo therapy using PD1 and/or 41BB antibodies (p < 0.0001). Ex vivotumor sample analysis revealed a significant reduction of MDSC & Tregs, and an increase of M1 type macrophages. In addition, loss of MDSC functionality and enhanced CD8+ T cell expansion was noticed. IHC of human tissue demonstrated enhanced LILRB2 expression, notably in colon and lung cancer. Conclusions: B57 OC has a unique binding profile to LILRB and KIR receptors. B57 OC induces anti-tumor activity in diverse syngeneic mouse models and acts synergistically with PD1 or 41BB antibodies. Pre-clinical and human in vitroexperiments demonstrate that B57 OC mode of action is established with inhibition of MDSCs, macrophage polarization to M1 phenotype, activation of NK cells and LILRB blockade on tumor cells, which in turn support the adaptive immune system by increasing CD8+ effector T cells and reducing Treg numbers. B57 OC is a first-in-class therapeutic with robust anti-tumor activity.

scholarly journals Immunological Features in the Process of Blood Platelet-Induced Alloimmunisation, with a Focus on Platelet Component Transfusion

Diseases ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 7 ◽  
Author(s):  
Olivier Garraud ◽  
Fabrice Cognasse ◽  
Pierre Moncharmont
Keyword(s):  
Human Leukocyte ◽  
Hla Class I ◽  
Blood Platelet ◽  
Short Review ◽  
Class I ◽  
Blood Group Antigens ◽  
Leukocyte Antigen ◽  
Copy Numbers ◽  
Hla Class I Molecules ◽  
Activated T Lymphocytes

Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties harboured on their foetuses’ cells (inherited from the father(s)) that may conflict with further pregnancies and transfused Platelet Components occasionally. This is possible since platelets constitutionally express HLA class I molecules (though in copy numbers that consistently differ among individuals). Platelets also express HPA moieties that are variants of naturally expressed adhesion and aggregation molecules; HPA differences between mothers and foetuses and between donors and recipients explain alloimmune conflicts and consequences. Lastly, platelets express ABO blood group antigens, which are rarely immunising, however transfusion mismatches in ABO groups seem to be related to immunisation in other blood and tissue groups. Transfusion also brings residual leukocytes that may also immunise through their copious copy numbers of HLA class I (rarely class II on activated T lymphocytes, B cells, and dendritic cells). In addition, residual red blood cells in platelet concentrates may induce anti-red blood cell allo-antibodies. This short review aims to present the main mechanisms that are commonly reported in alloimmunisation. It also critically endeavours to examine paths to either dampen alloimmunisation occurrences or to prevent them.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

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