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The Etiopathogenesis of Autoimmunity
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Howard Amital, Yehuda Shoenfeld
Infections also have the capacity to induce the synthesis of class II molecules on tissue cells that do not normally generate these antigens. It has been demonstrated that not only the genetic composition of the MHC class II, but also changes in the amount of surface molecules, determine the type and magnitude of antigen presentation and of the immune response.52 Population studies have demonstrated that patients with Graves’ and Hashimoto thyroiditis, as well as with type 1 diabetes mellitus and other autoimmune disorders, are associated with specific MHC class II alleles.52-53 The efficiency with which certain MHC class II allotypes present autoantigens may affect either failure or success to mount a productive immune response, and thereby determine the fate of the patient whether normal immune homeostasis will prevail or rather an autoimmune reaction will emerge.
The Human Immune System Seen from a Biomedical Engineering Viewpoint
Published in Robert B. Northrop, Endogenous and Exogenous Regulation and Control of Physiological Systems, 2020
For modeling purposes, Mϕs have been arbitrarily divided into three groups: inactivated, primed, and fully activated. In the inactivated condition, Mϕs can either be circulating or fixed in tissues. They have low oxygen consumption, little or no monokine (immunocytokine) secretion, and a low level of MHC class II gene expression. (MHC class II is an Mϕ membrane protein necessary for antigen presentation to helper T-cells.) Mature, inactivated Mϕs do have phagocytic activity, however, and can respond to chemotaxic signals and can proliferate in response to signals. Inactivated Mϕs are primed by gamma interferon (IFNγ) secreted from stimulated helper T-lymphocytes.
Precision
Published in Lawrence S. Chan, William C. Tang, Engineering-Medicine, 2019
By asking the question why cancer patients respond to immune-therapy, we know that MHC class II molecules on a given patient’s cancer cells are the key to provide strong T cell-target antigen recognition. What we have improved now is the speed this precision medicine process for making cancer vaccine, based on mRNA vaccine technology (Sahin et al. 2017). From sequence patients’ tumor mRNA on MHC class I and class II molecules to the vaccine delivery, the entire tumor targeting vaccine production time has been cut down to about 6 weeks.
A mathematical model of cytotoxic and helper T cell interactions in a tumour microenvironment
Published in Letters in Biomathematics, 2018
Heidi Dritschel, Sarah L. Waters, Andreas Roller, Helen M. Byrne
There are two populations of T cells, helper and cytotoxic, which are distinguished by their expression of CD4 and CD8 proteins, respectively. Naive helper T cells are activated by antigen presented with a major histocompatibility complex (MHC) class II molecule. (A glossary of the terminology used in this article is provided in Appendix 1.) Naive cytotoxic T cells are activated by antigen presented with an MHC class I molecule. Once activated the helper and cytotoxic T cells perform complementary functions to eliminate the tumour. Helper T cells further differentiate into subpopulations classified by the specific cytokines that they produce. In this way, they regulate multiple aspects of an immune response. For example, they promote the proliferation of cytotoxic T cells, they recruit and promote cells of the innate immune response, and they control levels of inflammation at the tumour site (Hung et al., 1998; Magombedze et al., 2013). (In this work, we do not distinguish these subpopulations.) Cytotoxic T cells scan the body for transformed cells (cancer cells) to which they bind before inducing cell killing.
Head Transplantation: The Immune System, Phantom Sensations, and the Integrated Mind
Published in The New Bioethics, 2018
In the vocabulary of immunology, the expressions ‘self’ and ‘non-self’ may be thrown about with such abandon that these expressions are easily used to conflate issues in the broader language of personhood. It is important, therefore, to remember that when these expressions are used in immunology they are concerned with molecular recognition. The immune system consists of a network of molecular and cellular systems that undertake the critical function of differentiating that which is described in immunological terms as ‘self’ from that which is ‘non-self’ and imposes a level of identity on cells and tissues that must be considered in any transplant operation. These systems are typically grouped under the general headings ‘innate immunity’ and ‘adaptive immunity’ and involve more than 1600 genes (Abbas et al. 2005). Underpinning the adaptive responses are protein complexes brought together under the general heading the ‘major histocompatibility complex’ (MHC), also referred to as ‘human leukocyte antigens’ (HLA) when specific human MHC proteins are being referenced. MHC antigens are grouped into a number of classes, which, in broad terms, might be said to share function, insofar as they may, for example, process proteins into small chunks that are then presented to the T-cell receptor (TcR) on T-cells (La Gruta et al. 2018). They do, however, differ structurally from each other and serve different specific tasks. One of these, MHC class I (MHC-I, of which HLA-A, HLA-B, and HLA-C are members), is normally present on all nucleated cells, and subclasses of this are expressed within the first three days of the life of a human embryo (Wang et al. 2009). The absence MHC-I expression on cells leaves them vulnerable to destruction through the action of the MHC-I-sensing ‘killer cell immunoglobulin-like receptor’ (KIR), present on subpopulations of immune cells known as Natural Killer (NK) cells and subsets of T-cells. An important exception to this is the red blood cell population. Red cells do not express MHC-I, instead escaping destruction by NK cells through the expression of another protein, CD47 (Wang et al. 2010). Alongside the MHC-I, the expression of MHC class II (MHC-II, comprising HLA-DP HLA-DQ and HLA-DR in humans) and minor histocompatibility antigens (MiHA) like the male-specific H-Y antigen. The result of this is that, by the 8-cell stage of the embryo, the embryo is immunologically reactive with respect to the mother and its continued development requires the induction of immunological tolerance within the womb to prevent fetal rejection and miscarriage (Fernandez et al. 1999; Larsen et al. 2013; Colucci 2017).