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Histocompatibility
Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult. Discovery The discovery of the MHC and role of histocompatibility in transplantation was a combined effort of many scientists in the 20t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Major Histocompatibility Complex
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules. This locus got its name because it was discovered via the study of transplanted tissue compatibility. Later studies revealed that tissue rejection due to incompatibility is only a facet of the full function of MHC molecules: binding an antigen derived from self-proteins, or from pathogens, and bringing the antigen presentation to the cell surface for recognition by the appropriate T-cells. MHC molecules mediate the interactions of leukocytes, also called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's susceptibility to autoimmune diseases. In a cell, protein molecules of the host's own phenotype or of other biologic entit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Human Leukocyte Antigen
The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for the regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals. Mutations in HLA genes may be linked to autoimmune disease such as type I diabetes, and celiac disease. The HLA gene complex resides on a 3 Mbp stretch within chromosome 6, p-arm at 21.3. HLA genes are highly polymorphic, which means that they have many different alleles, allowing them to fine-tune the adaptive immune system. The proteins encoded by certain genes are also known as ''antigens'', as a result of their historic discovery as factors in organ transplants. HLAs corresponding to MHC class I ( A, B, and C), all of which are the HLA Class1 group, present peptides from inside the cell. For example, if the cell is infected by a virus, the HLA system brings f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MHC Class II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses. The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I). Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface. In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR. Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a ty ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MHC Class I
MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called ''cytosolic'' or ''endogenous pathway''. In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, and HLA-C. Function Class I MHC molecules bind peptides generated mainly from degradation of cytosolic proteins by the proteasome. The MHC I:peptide complex is then inserted via endoplasmic reticulum in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transplant Rejection
Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant. Types of transplant rejection Transplant rejection can be classified into three types: hyperacute, acute, and chronic. These types are differentiated by how quickly the recipient's immune system is activated and the specific aspect or aspects of immunity involved. Hyperacute rejection Hyperacute rejection is a form of rejection that manifests itself in the minutes to hours following transplantation. It is caused by the presence of pre-existing antibodies in the recipient that recognize antigens in the donor organ. These antigens are located on the endothelial lining of blood vessels within the transplanted organ and, once antibodies bind, will lead to the rapid activation of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HLA-A
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans. MHC Class I molecules such as HLA-A are part of a process that presents short polypeptides to the immune system. These polypeptides are typically 7-11 amino acids in length and originate from proteins being expressed by the cell. There are two classes of polypeptide that can be presented by an HLA protein: those that are supposed to be expre ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
George Davis Snell
George Davis Snell NAS (December 19, 1903 – June 6, 1996) was an American mouse geneticist and basic transplant immunologist. Work George Snell shared the 1980 Nobel Prize in Physiology or Medicine with Baruj Benacerraf and Jean Dausset for their discoveries concerning "genetically determined structures on the cell surface that regulate immunological reactions". Snell specifically "discovered the genetic factors that determine the possibilities of transplanting tissue from one individual to another. It was Snell who introduced the concept of H antigensSnell's work in mice led to the discovery of Human leukocyte antigen, HLA, the major histocompatibility complex, in humans (and all vertebrates) that is analogous to the H-2 complex in mice. Recognition of these key genes was prerequisite to successful tissue and organ transplantation. Life George Snell was born in Bradford, Massachusetts, the youngest of three children. His father (who was born in Minnesota) worked as a s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Jean Dausset
Jean-Baptiste-Gabriel-Joachim Dausset (19 October 1916 – 6 June 2009) was a French immunologist born in Toulouse, France. Dausset received the Nobel Prize in Physiology or Medicine in 1980 along with Baruj Benacerraf and George Davis Snell for their discovery and characterisation of the genes making the major histocompatibility complex. Using the money from his Nobel Prize and a grant from the French Television, Dausset founded the Human Polymorphism Study Center ( CEPH) in 1984, which was later renamed the Foundation Jean Dausset-CEPH in his honour. He married Rose Mayoral in 1963, with whom he had two children, Henri and Irène. Jean Dausset died on June 6, 2009 in Majorca, Spain, at the age of 92. Early life Jean-Baptiste-Gabriel-Joachim Dausset was born on 19 October 1916, in Toulouse, France. He was the youngest of four children of Henri Dausset and Elisabeth Dausset (born Renard). His father was from the Pyrénées, and was a doctor by profession, and his mother was a h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chromosomal or genomic location of a gene or any other genetic element is called a locus (plural: loci) and alternative DNA sequences at a locus are called alleles." The simplest alleles are single nucleotide polymorphisms (SNP). but they can also be insertions and deletions of up to several thousand base pairs. Popular definitions of 'allele' typically refer only to different alleles within genes. For example, the ABO blood grouping is controlled by the ABO gene, which has six common alleles (variants). In population genetics, nearly every living human's phenotype for the ABO gene is some combination of just these six alleles. Most alleles observed result in little or no change in the function of the gene product it codes for. However, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genetic Polymorphism
A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic. Gene polymorphisms can occur in any region of the genome. The majority of polymorphisms are silent, meaning they do not alter the function or expression of a gene. Some polymorphisms are visible. For example, in dogs the E locus can have any of five different alleles, known as E, Em, Eg, Eh, and e. Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats. A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein; this abnormality may cause or be associated with disease. For example, a polymorphic variant of the gene encoding the enzyme CYP4A11, in which thymidine replaces cytosine at the gene's ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HLA-DP
HLA-DP is a protein/peptide-antigen receptor and graft-versus-host disease antigen that is composed of 2 subunits, DPα and DPβ. DPα and DPβ are encoded by two loci, HLA-DPA1 and HLA-DPB1, that are found in the MHC Class II (or HLA-D) region in the Human Leukocyte Antigen complex on human chromosome 6 (see protein boxes on right for links). Less is known about HLA-DP relative to HLA-DQ and HLA-DR but the sequencing of DP types and determination of more frequent haplotypes has progressed greatly within the last few years. Structure, Functions, Genetics Structure HLA-DP is an αβ-heterodimer cell-surface receptor. Each DP subunit (α-subunit, β-subunit) is composed of a α-helical N-terminal domain, an IgG-like β-sheet, a membrane spanning domain, and a cytoplasmic domain. The α-helical domain forms the sides of the peptide binding groove. The β-sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) bi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Graft-versus-host Disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which remain within the donated tissue (the graft) recognize the recipient (the host) as foreign (non-self). The white blood cells present within the transplanted tissue then attack the recipient's body's cells, which leads to GvHD. This should not be confused with a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue; GvHD occurs when the donor's immune system's white blood cells reject the recipient. The underlying principle ( alloimmunity) is the same, but the details and course may differ. GvHD can also occur after a blood transfusion if the blood products used have not been irradiated or treated with an approved pathogen reduction system. Types In the clinical setting, graft-versus-h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
