Different mutations are created in the commercial host strains of E.coli which provide them with advantages as compared to the wild type strain. This presentation deals with few strains like Dh5alpha, DH10B, Bl21, JM109 E.coli strains and their associated mutations.
General organization and inheritance of MHCSOURIKDEY1
The document summarizes key aspects of the major histocompatibility complex (MHC):
1) MHC genes are organized into three classes - Class I genes present antigens to cytotoxic T cells, Class II genes present antigens to helper T cells, and Class III genes encode proteins involved in immune responses.
2) MHC genes show high levels of polymorphism between individuals and encode cell surface proteins that play an important role in the immune system by distinguishing self from non-self.
3) MHC is inherited as haplotypes from each parent, resulting in individuals expressing two sets of MHC molecules and high diversity in human populations.
1. The intracellular trafficking of CD1a allows it to efficiently present the glycolipid antigen sulfatide to CD1a-restricted T cells.
2. Sulfatide is primarily localized to early endocytic and recycling compartments, where CD1a also localizes due to its unique trafficking pattern.
3. When CD1a was engineered to traffic to lysosomes like CD1b instead of recycling compartments, it lost the ability to efficiently present sulfatide over time. This demonstrates the importance of matching a antigen's trafficking route with the trafficking of its presenting molecule.
Sima lev: Lipid Transfer Proteins and Membrane Contact Sites in Human CancerSima Lev
Lipid-transfer proteins (LTPs) were initially discovered as cytosolic factors that facilitate lipid transport between membrane bilayers in vitro. Since then, many LTPs have been isolated from bacteria, plants, yeast, and mammals, and extensively studied in cell-free systems and intact cells. A major advance in the LTP field was associated with the discovery of intracellular membrane contact sites (MCSs), small cytosolic gaps between the endoplasmic reticulum (ER) and other cellular membranes, which accelerate lipid transfer by LTPs. As LTPs modulate the distribution of lipids within cellular membranes, and many lipid species function as second messengers in key signaling pathways that control cell survival, proliferation, and migration, LTPs have been implicated in cancer-associated signal transduction cascades. Increasing evidence suggests that LTPs play an important role in cancer progression and metastasis. This review by Sima Lev describes how different LTPs as well as MCSs can contribute to cell transformation and malignant phenotype, and discusses how “aberrant” MCSs are associated with tumorigenesis in human.
This document discusses diabetes, including its types, symptoms, causes, prevention, and facts. Diabetes is a group of metabolic diseases characterized by high blood sugar due to either lack of insulin production or cells not responding properly to insulin. The main types are type 1, caused by destruction of insulin-producing cells, and type 2, often related to lifestyle. Symptoms include frequent urination, thirst, fatigue, and hunger. Prevention focuses on healthy eating, physical activity, and weight control. Complications can be reduced through proper treatment and control of blood glucose levels.
Tugas bahasa Indonesia membahas cara mencegah diabetes melitus dengan menjaga gaya hidup seimbang melalui diet seimbang, olahraga teratur, dan menjaga berat badan. Gejala diabetes melitus antara lain poliuria, polidipsia, polifagia, dan penurunan berat badan.
Diabetes is a disease where the body does not produce enough or properly use insulin, a hormone that allows glucose to enter cells and be used for energy. Without enough insulin, glucose builds up in the bloodstream leading to high blood glucose levels which can damage the heart, eyes, nerves, and kidneys if left untreated. There are three main types of diabetes: Type 1 where the body does not produce insulin; Type 2 where the body does not produce enough insulin or use it properly, often affecting overweight people; and gestational diabetes which occurs during pregnancy but usually disappears after.
Different mutations are created in the commercial host strains of E.coli which provide them with advantages as compared to the wild type strain. This presentation deals with few strains like Dh5alpha, DH10B, Bl21, JM109 E.coli strains and their associated mutations.
General organization and inheritance of MHCSOURIKDEY1
The document summarizes key aspects of the major histocompatibility complex (MHC):
1) MHC genes are organized into three classes - Class I genes present antigens to cytotoxic T cells, Class II genes present antigens to helper T cells, and Class III genes encode proteins involved in immune responses.
2) MHC genes show high levels of polymorphism between individuals and encode cell surface proteins that play an important role in the immune system by distinguishing self from non-self.
3) MHC is inherited as haplotypes from each parent, resulting in individuals expressing two sets of MHC molecules and high diversity in human populations.
1. The intracellular trafficking of CD1a allows it to efficiently present the glycolipid antigen sulfatide to CD1a-restricted T cells.
2. Sulfatide is primarily localized to early endocytic and recycling compartments, where CD1a also localizes due to its unique trafficking pattern.
3. When CD1a was engineered to traffic to lysosomes like CD1b instead of recycling compartments, it lost the ability to efficiently present sulfatide over time. This demonstrates the importance of matching a antigen's trafficking route with the trafficking of its presenting molecule.
Sima lev: Lipid Transfer Proteins and Membrane Contact Sites in Human CancerSima Lev
Lipid-transfer proteins (LTPs) were initially discovered as cytosolic factors that facilitate lipid transport between membrane bilayers in vitro. Since then, many LTPs have been isolated from bacteria, plants, yeast, and mammals, and extensively studied in cell-free systems and intact cells. A major advance in the LTP field was associated with the discovery of intracellular membrane contact sites (MCSs), small cytosolic gaps between the endoplasmic reticulum (ER) and other cellular membranes, which accelerate lipid transfer by LTPs. As LTPs modulate the distribution of lipids within cellular membranes, and many lipid species function as second messengers in key signaling pathways that control cell survival, proliferation, and migration, LTPs have been implicated in cancer-associated signal transduction cascades. Increasing evidence suggests that LTPs play an important role in cancer progression and metastasis. This review by Sima Lev describes how different LTPs as well as MCSs can contribute to cell transformation and malignant phenotype, and discusses how “aberrant” MCSs are associated with tumorigenesis in human.
This document discusses diabetes, including its types, symptoms, causes, prevention, and facts. Diabetes is a group of metabolic diseases characterized by high blood sugar due to either lack of insulin production or cells not responding properly to insulin. The main types are type 1, caused by destruction of insulin-producing cells, and type 2, often related to lifestyle. Symptoms include frequent urination, thirst, fatigue, and hunger. Prevention focuses on healthy eating, physical activity, and weight control. Complications can be reduced through proper treatment and control of blood glucose levels.
Tugas bahasa Indonesia membahas cara mencegah diabetes melitus dengan menjaga gaya hidup seimbang melalui diet seimbang, olahraga teratur, dan menjaga berat badan. Gejala diabetes melitus antara lain poliuria, polidipsia, polifagia, dan penurunan berat badan.
Diabetes is a disease where the body does not produce enough or properly use insulin, a hormone that allows glucose to enter cells and be used for energy. Without enough insulin, glucose builds up in the bloodstream leading to high blood glucose levels which can damage the heart, eyes, nerves, and kidneys if left untreated. There are three main types of diabetes: Type 1 where the body does not produce insulin; Type 2 where the body does not produce enough insulin or use it properly, often affecting overweight people; and gestational diabetes which occurs during pregnancy but usually disappears after.
This document discusses HLA typing and its role in tissue transplantation. It begins by introducing the major histocompatibility complex (MHC) and its role in transplant rejection. It then describes MHC polymorphism, HLA nomenclature, and various methods for HLA typing including serology and molecular techniques. The document concludes by discussing the applications of HLA typing in organ transplantation, including the mechanisms of allograft recognition and rejection.
Some potential causes of the immune system attacking the self in autoimmune diseases include:
- Genetic predisposition - Genes coding for the variety of MHC molecules can influence susceptibility. A T cell's ability to respond is determined by MHC genotype. Differences in MHC alleles' ability to present autoantigens can play a role.
- Environmental triggers - Factors like infections, drugs, trauma, etc. may trigger autoimmunity in genetically susceptible individuals by molecular mimicry or other mechanisms.
- Loss of tolerance - Failure to eliminate self-reactive lymphocytes during development or maintain peripheral tolerance can allow self-reactivity.
- Hormonal factors - Many autoimmune diseases are more common in women and fluctuate with horm
The document discusses several topics related to genetics of immunity:
1. It describes the major histocompatibility complex (MHC) genes which are highly polymorphic and play a key role in self/non-self recognition. They are involved in several autoimmune diseases.
2. Several inherited immunodeficiencies are summarized, including defects in phagocytic function like chronic granulomatous disease, humoral deficiencies like Bruton's agammaglobulinemia, and combined or cellular deficiencies such as DiGeorge syndrome.
3. The Rhesus factor, its role in hemolytic disease of the newborn, and RNA/mRNA vaccines which work by introducing mRNA to reprogram cells
1) Dendritic cells present antigens to T cells through both Class I MHC and CD1 complexes. Antigen presentation through these pathways occurs through processing in endosomal compartments.
2) Pathogen recognition receptors like TLRs modulate antigen processing and presentation by inducing dendritic cell maturation and rearrangement of intracellular trafficking. This promotes the generation and surface display of peptide-MHC and lipid-CD1 complexes.
3) Triggering of pathogen recognition receptors also regulates endosomal composition and antigen degradation, which influences the generation of complexes that can stimulate T cell responses.
The Major Histocompatibility Complex (MHC) is a set of genes located on chromosome 6 that encode MHC molecules displayed on cell surfaces. MHC molecules control the immune response through recognition of self and non-self antigens. There are two main classes of MHC molecules - Class I molecules present intracellular peptides to CD8+ T cells, while Class II molecules present extracellular peptides internalized by antigen presenting cells to CD4+ T cells. MHC molecules play a crucial role in the immune system through antigen presentation and recognition.
This document discusses histocompatibility in kidney transplantation. It describes the discovery of human leukocyte antigens (HLAs) in 1958 and how they are encoded on chromosome 6. It then summarizes HLA Class I and Class II loci, how they present antigens, and the techniques used for HLA typing, including comparing CDC, FCXM, SPI, SAB, and epitope matching methods. The document also discusses HLA-specific allosensitization, antibody detection and risk assessment, and the virtual crossmatch.
The document discusses HLA typing and its implications. It begins with a brief history of the discovery of the major histocompatibility complex (MHC) in mice and humans. It then describes the structure and functions of the MHC, including the class I, class II, and class III regions. The document discusses methods of HLA typing, including serological testing using microcytotoxicity and molecular methods. It notes some implications of HLA typing, such as its role in organ transplant matching and susceptibility to autoimmune disease.
This document discusses HLA (Human Leucocyte Antigen) typing methods. It describes that HLA forms part of the Major Histocompatibility Complex found on chromosome 6 and plays an essential role in the immune response. It summarizes various HLA typing methods including serology, cellular typing, and molecular methods such as PCR-SSP, PCR-SSOP, sequencing-based typing, and Luminex technology. It provides details on the procedures and advantages and disadvantages of each method.
The document summarizes the major histocompatibility complex (MHC). It discusses how the MHC was discovered through studies of tissue transplantation in mice. The MHC locus contains genes that encode MHC class I and class II molecules that present antigens to T cells and play a key role in immune responses. MHC molecules are expressed on nearly all nucleated cells for class I and specifically on antigen presenting cells for class II. The genomic organization and structures of MHC class I and II molecules allow them to present peptides to CD8+ or CD4+ T cells, respectively.
Human leucocyte antigen (HLA) typing began with studies of mouse transplantation experiments in the 1930s. This led to the discovery of the major histocompatibility complex (MHC) in mice and humans. Early work established the genetic basis of the immune response and immune regulation. HLA typing methods have evolved from serology using antisera to current molecular techniques like PCR. HLA plays a key role in transplant matching and understanding the immune system.
The weak D phenotype is thought to arise from several mechanisms. .pdfmckenziecast21211
The weak D phenotype is thought to arise from several mechanisms. Which one of the following
statements is false?
C gene is in trans position to D gene, this results in a weakening influence on the D gene,
examples CDe/Cde and cDe/Cde.
Weak D antigen is genetically transmitted. This can occur rarely in R1 and R2 genotypes in
caucasians. Also occurs in the Ro genotype in certain racial groups more commonly.
The D antigen consists of multiple pieces (is a mosaic). Occasionally one or more of these pieces
is missing. The red cells are said to have a partial D.
D deletion genes gives rise to weakened expression of D antigen.
Rh null cells lack:
MNSs antigens.
Lewis antigens.
Normal oxygen-carrying capacity.
Rh antigens.
There are two closely related and closely linked genes.
Enzyme techniques, in conjunction with an IgM anti-D.
Increasing the time for the incubation of the saline phase.
Performance of an IAT using an IgG anti-D.
Don\'t need to do it in a blood bank.
C gene is in trans position to D gene, this results in a weakening influence on the D gene,
examples CDe/Cde and cDe/Cde.
Weak D antigen is genetically transmitted. This can occur rarely in R1 and R2 genotypes in
caucasians. Also occurs in the Ro genotype in certain racial groups more commonly.
The D antigen consists of multiple pieces (is a mosaic). Occasionally one or more of these
pieces is missing. The red cells are said to have a partial D.
D deletion genes gives rise to weakened expression of D antigen.
Solution
The weak D phenotype is thought to arise from several mechanisms. Which one of the following
statements is false?
D deletion genes gives rise to weakened expression of D antigen.
Rh null cells lack:
Rh antigens.
There are two closely related and closely linked genes.
Enzyme techniques, in conjunction with an IgM anti-D.
Increasing the time for the incubation of the saline phase.
Performance of an IAT using an IgG anti-D.
Don\'t need to do it in a blood bank.
Last one is an incomplete question
D deletion genes gives rise to weakened expression of D antigen..
Major Histocompatibility complex & Antigen Presentation and ProcessingSreeraj Thamban
The document discusses the major histocompatibility complex (MHC) and antigen processing and presentation. It describes MHC molecules as polymorphic glycoproteins that play a role in discriminating self from non-self and participate in both humoral and cell-mediated immunity. MHC class I molecules present endogenous antigens on most nucleated cells and interact with CD8+ T cells. MHC class II molecules present exogenous antigens on antigen-presenting cells and interact with CD4+ T cells. Antigens are processed into peptides of appropriate size and bound motifs to be presented in the binding groove of MHC molecules.
This document discusses stem cell transplantation and histocompatibility. It explains that stem cell transplants can be rejected by the recipient's immune system, so the transplanted cells must closely match the recipient to avoid being recognized as foreign. To determine if a donor is a good immunological match, a tissue typing test identifies HLA antigens on immune cells; identical HLA antigens indicate a good match. The document provides background on HLA antigens and their role in the immune response and histocompatibility in stem cell transplantation.
The major histocompatibility complex (MHC) is a cluster of genes found in all mammals that encodes proteins important for the immune system to distinguish self from non-self. MHC molecules are expressed on the cell surface and present peptide antigens to T cells. There are three main classes of MHC genes - class I presents endogenous peptides to cytotoxic T cells, class II presents exogenous peptides to helper T cells, and class III encodes non-antigen presenting proteins involved in immunity. MHC molecules have binding sites that allow them to bind a variety of peptide antigens through anchor residues, helping the immune system recognize a diverse array of pathogens. Polymorphism of MHC alleles within populations helps provide protection against rapidly mutating pathogens.
This document discusses the role of HLA (human leukocyte antigen) genes in various skin diseases. It begins by describing HLA structure and function, noting that HLA genes encode antigen-presenting molecules and play a key role in the immune system. The document then examines associations between specific HLA alleles and a wide range of inflammatory, autoimmune, and infectious skin diseases. It also reviews how HLA type can influence susceptibility to drug eruptions and metabolic disorders. In conclusion, the author states that studying HLA associations with skin disease can provide insights into disease diagnosis, prognosis, clinical course, and potential new therapies.
This document provides information on MHC class I and class II molecules, including their structure, function, and role in antigen presentation. It discusses that MHC class I molecules are expressed on all nucleated cells and present intracellular antigens to CD8+ T cells. MHC class II molecules are expressed primarily on antigen presenting cells and present extracellular antigens to CD4+ T cells. The peptide binding grooves of MHC class I and II molecules differ in their structure and the size of peptides they can bind.
1) HLA-DM plays a critical role in loading and editing peptides on MHC class II molecules. It induces dissociation of peptides from MHCII, favoring display of high-affinity peptides and performing an important editing function.
2) The interaction of MHCII molecules and HLA-DM depends on the occupancy state of the peptide binding groove. Empty MHCII molecules form stable complexes with HLA-DM that are disrupted by binding of high-affinity peptide.
3) HLA-DM binds to a short-lived transition state in which the N-terminal peptide segment has transiently disengaged from key interactions with the peptide binding groove due to spontaneous peptide motion. This favors the removal of low-affinity
Class I and class II MHC molecules are membrane-bound glycoproteins that present antigenic peptides to T cells. Class I MHC molecules present intracellular peptides to CD8+ T cells and are expressed on all nucleated cells. They are composed of an alpha chain associated with beta-2 microglobulin. Class II MHC molecules present extracellular peptides to CD4+ T cells and are expressed mainly on antigen presenting cells. They are composed of alpha and beta chains. Viruses can induce malignant cell transformation by encoding oncoproteins that alter normal cell growth properties.
This document discusses the role of MHC (Major Histocompatibility Complex, also known as HLA in humans) in organ transplantation and tolerance induction. It notes that while MHC matching has traditionally been important for kidney allocation, some studies question its role. The document then outlines long-term health problems experienced by transplant recipients related to immunosuppression. It presents facts that are difficult for immunology to explain, and proposes an MHC-based suppression theory for controlling T cells using MHC-derived peptides. The theory involves T cells receiving an identity signal when responding to a single clone versus multiple clones. Evidence supporting the MBS theory is discussed.
This document discusses HLA typing and its role in tissue transplantation. It begins by introducing the major histocompatibility complex (MHC) and its role in transplant rejection. It then describes MHC polymorphism, HLA nomenclature, and various methods for HLA typing including serology and molecular techniques. The document concludes by discussing the applications of HLA typing in organ transplantation, including the mechanisms of allograft recognition and rejection.
Some potential causes of the immune system attacking the self in autoimmune diseases include:
- Genetic predisposition - Genes coding for the variety of MHC molecules can influence susceptibility. A T cell's ability to respond is determined by MHC genotype. Differences in MHC alleles' ability to present autoantigens can play a role.
- Environmental triggers - Factors like infections, drugs, trauma, etc. may trigger autoimmunity in genetically susceptible individuals by molecular mimicry or other mechanisms.
- Loss of tolerance - Failure to eliminate self-reactive lymphocytes during development or maintain peripheral tolerance can allow self-reactivity.
- Hormonal factors - Many autoimmune diseases are more common in women and fluctuate with horm
The document discusses several topics related to genetics of immunity:
1. It describes the major histocompatibility complex (MHC) genes which are highly polymorphic and play a key role in self/non-self recognition. They are involved in several autoimmune diseases.
2. Several inherited immunodeficiencies are summarized, including defects in phagocytic function like chronic granulomatous disease, humoral deficiencies like Bruton's agammaglobulinemia, and combined or cellular deficiencies such as DiGeorge syndrome.
3. The Rhesus factor, its role in hemolytic disease of the newborn, and RNA/mRNA vaccines which work by introducing mRNA to reprogram cells
1) Dendritic cells present antigens to T cells through both Class I MHC and CD1 complexes. Antigen presentation through these pathways occurs through processing in endosomal compartments.
2) Pathogen recognition receptors like TLRs modulate antigen processing and presentation by inducing dendritic cell maturation and rearrangement of intracellular trafficking. This promotes the generation and surface display of peptide-MHC and lipid-CD1 complexes.
3) Triggering of pathogen recognition receptors also regulates endosomal composition and antigen degradation, which influences the generation of complexes that can stimulate T cell responses.
The Major Histocompatibility Complex (MHC) is a set of genes located on chromosome 6 that encode MHC molecules displayed on cell surfaces. MHC molecules control the immune response through recognition of self and non-self antigens. There are two main classes of MHC molecules - Class I molecules present intracellular peptides to CD8+ T cells, while Class II molecules present extracellular peptides internalized by antigen presenting cells to CD4+ T cells. MHC molecules play a crucial role in the immune system through antigen presentation and recognition.
This document discusses histocompatibility in kidney transplantation. It describes the discovery of human leukocyte antigens (HLAs) in 1958 and how they are encoded on chromosome 6. It then summarizes HLA Class I and Class II loci, how they present antigens, and the techniques used for HLA typing, including comparing CDC, FCXM, SPI, SAB, and epitope matching methods. The document also discusses HLA-specific allosensitization, antibody detection and risk assessment, and the virtual crossmatch.
The document discusses HLA typing and its implications. It begins with a brief history of the discovery of the major histocompatibility complex (MHC) in mice and humans. It then describes the structure and functions of the MHC, including the class I, class II, and class III regions. The document discusses methods of HLA typing, including serological testing using microcytotoxicity and molecular methods. It notes some implications of HLA typing, such as its role in organ transplant matching and susceptibility to autoimmune disease.
This document discusses HLA (Human Leucocyte Antigen) typing methods. It describes that HLA forms part of the Major Histocompatibility Complex found on chromosome 6 and plays an essential role in the immune response. It summarizes various HLA typing methods including serology, cellular typing, and molecular methods such as PCR-SSP, PCR-SSOP, sequencing-based typing, and Luminex technology. It provides details on the procedures and advantages and disadvantages of each method.
The document summarizes the major histocompatibility complex (MHC). It discusses how the MHC was discovered through studies of tissue transplantation in mice. The MHC locus contains genes that encode MHC class I and class II molecules that present antigens to T cells and play a key role in immune responses. MHC molecules are expressed on nearly all nucleated cells for class I and specifically on antigen presenting cells for class II. The genomic organization and structures of MHC class I and II molecules allow them to present peptides to CD8+ or CD4+ T cells, respectively.
Human leucocyte antigen (HLA) typing began with studies of mouse transplantation experiments in the 1930s. This led to the discovery of the major histocompatibility complex (MHC) in mice and humans. Early work established the genetic basis of the immune response and immune regulation. HLA typing methods have evolved from serology using antisera to current molecular techniques like PCR. HLA plays a key role in transplant matching and understanding the immune system.
The weak D phenotype is thought to arise from several mechanisms. .pdfmckenziecast21211
The weak D phenotype is thought to arise from several mechanisms. Which one of the following
statements is false?
C gene is in trans position to D gene, this results in a weakening influence on the D gene,
examples CDe/Cde and cDe/Cde.
Weak D antigen is genetically transmitted. This can occur rarely in R1 and R2 genotypes in
caucasians. Also occurs in the Ro genotype in certain racial groups more commonly.
The D antigen consists of multiple pieces (is a mosaic). Occasionally one or more of these pieces
is missing. The red cells are said to have a partial D.
D deletion genes gives rise to weakened expression of D antigen.
Rh null cells lack:
MNSs antigens.
Lewis antigens.
Normal oxygen-carrying capacity.
Rh antigens.
There are two closely related and closely linked genes.
Enzyme techniques, in conjunction with an IgM anti-D.
Increasing the time for the incubation of the saline phase.
Performance of an IAT using an IgG anti-D.
Don\'t need to do it in a blood bank.
C gene is in trans position to D gene, this results in a weakening influence on the D gene,
examples CDe/Cde and cDe/Cde.
Weak D antigen is genetically transmitted. This can occur rarely in R1 and R2 genotypes in
caucasians. Also occurs in the Ro genotype in certain racial groups more commonly.
The D antigen consists of multiple pieces (is a mosaic). Occasionally one or more of these
pieces is missing. The red cells are said to have a partial D.
D deletion genes gives rise to weakened expression of D antigen.
Solution
The weak D phenotype is thought to arise from several mechanisms. Which one of the following
statements is false?
D deletion genes gives rise to weakened expression of D antigen.
Rh null cells lack:
Rh antigens.
There are two closely related and closely linked genes.
Enzyme techniques, in conjunction with an IgM anti-D.
Increasing the time for the incubation of the saline phase.
Performance of an IAT using an IgG anti-D.
Don\'t need to do it in a blood bank.
Last one is an incomplete question
D deletion genes gives rise to weakened expression of D antigen..
Major Histocompatibility complex & Antigen Presentation and ProcessingSreeraj Thamban
The document discusses the major histocompatibility complex (MHC) and antigen processing and presentation. It describes MHC molecules as polymorphic glycoproteins that play a role in discriminating self from non-self and participate in both humoral and cell-mediated immunity. MHC class I molecules present endogenous antigens on most nucleated cells and interact with CD8+ T cells. MHC class II molecules present exogenous antigens on antigen-presenting cells and interact with CD4+ T cells. Antigens are processed into peptides of appropriate size and bound motifs to be presented in the binding groove of MHC molecules.
This document discusses stem cell transplantation and histocompatibility. It explains that stem cell transplants can be rejected by the recipient's immune system, so the transplanted cells must closely match the recipient to avoid being recognized as foreign. To determine if a donor is a good immunological match, a tissue typing test identifies HLA antigens on immune cells; identical HLA antigens indicate a good match. The document provides background on HLA antigens and their role in the immune response and histocompatibility in stem cell transplantation.
The major histocompatibility complex (MHC) is a cluster of genes found in all mammals that encodes proteins important for the immune system to distinguish self from non-self. MHC molecules are expressed on the cell surface and present peptide antigens to T cells. There are three main classes of MHC genes - class I presents endogenous peptides to cytotoxic T cells, class II presents exogenous peptides to helper T cells, and class III encodes non-antigen presenting proteins involved in immunity. MHC molecules have binding sites that allow them to bind a variety of peptide antigens through anchor residues, helping the immune system recognize a diverse array of pathogens. Polymorphism of MHC alleles within populations helps provide protection against rapidly mutating pathogens.
This document discusses the role of HLA (human leukocyte antigen) genes in various skin diseases. It begins by describing HLA structure and function, noting that HLA genes encode antigen-presenting molecules and play a key role in the immune system. The document then examines associations between specific HLA alleles and a wide range of inflammatory, autoimmune, and infectious skin diseases. It also reviews how HLA type can influence susceptibility to drug eruptions and metabolic disorders. In conclusion, the author states that studying HLA associations with skin disease can provide insights into disease diagnosis, prognosis, clinical course, and potential new therapies.
This document provides information on MHC class I and class II molecules, including their structure, function, and role in antigen presentation. It discusses that MHC class I molecules are expressed on all nucleated cells and present intracellular antigens to CD8+ T cells. MHC class II molecules are expressed primarily on antigen presenting cells and present extracellular antigens to CD4+ T cells. The peptide binding grooves of MHC class I and II molecules differ in their structure and the size of peptides they can bind.
1) HLA-DM plays a critical role in loading and editing peptides on MHC class II molecules. It induces dissociation of peptides from MHCII, favoring display of high-affinity peptides and performing an important editing function.
2) The interaction of MHCII molecules and HLA-DM depends on the occupancy state of the peptide binding groove. Empty MHCII molecules form stable complexes with HLA-DM that are disrupted by binding of high-affinity peptide.
3) HLA-DM binds to a short-lived transition state in which the N-terminal peptide segment has transiently disengaged from key interactions with the peptide binding groove due to spontaneous peptide motion. This favors the removal of low-affinity
Class I and class II MHC molecules are membrane-bound glycoproteins that present antigenic peptides to T cells. Class I MHC molecules present intracellular peptides to CD8+ T cells and are expressed on all nucleated cells. They are composed of an alpha chain associated with beta-2 microglobulin. Class II MHC molecules present extracellular peptides to CD4+ T cells and are expressed mainly on antigen presenting cells. They are composed of alpha and beta chains. Viruses can induce malignant cell transformation by encoding oncoproteins that alter normal cell growth properties.
This document discusses the role of MHC (Major Histocompatibility Complex, also known as HLA in humans) in organ transplantation and tolerance induction. It notes that while MHC matching has traditionally been important for kidney allocation, some studies question its role. The document then outlines long-term health problems experienced by transplant recipients related to immunosuppression. It presents facts that are difficult for immunology to explain, and proposes an MHC-based suppression theory for controlling T cells using MHC-derived peptides. The theory involves T cells receiving an identity signal when responding to a single clone versus multiple clones. Evidence supporting the MBS theory is discussed.
2. Non-classical Play accessory roles in the antigen loading
process . Examples: HLA-DM , HLA-DO
Low Polymorphism
Classical
High Polymorphism
Bind to peptide antigens and present them to
T cells . Examples: HLA-DP , DQ , DR
4. Has a well-understood function in catalyzing peptide
exchange on MHCII proteins
After CLIP release DM stabilizes the intermediate
empty MHC class II molecules
In Mice : H2M (H2DM)
HLA-DM Deficiency The ability of APCs to present
either protein or peptide antigen is severely
compromised.
5.
6. Structure : Heterodimer (Alpha and Beta)
Gene Locus : HLA-DOA and HLA-DOB in MHC
class II region of the MHC gene complex
7. Not expressed at the cell surface
Has a high degree of similarity to classical class II
MHC
In RER:HLA-DO,DM and DR synthesis Transport to
Golgi and MIIC (MHC Class II Compartment)
DO and DM molecules always bind in a side-by-side
arrangement
8.
9. HLA-DO has a limited tissue distribution :
B Lymphocytes
Thymic Medullary Epithelial Cells
Trophoblasts
Subpopulations of dendritic cells(especially BCDA3+
plasmacytoid DCs)
Human dendritic cells cultured with GM-CSF have
been reported to express HLA-DO
10. HLA-DO is not induced by the class II transactivator (CIITA)
In mice: H2-O
11. Forms a tight complex with DM and inhibit it
Might play a role in tolerance induction
12. DO functions as a substrate mimic, by binding tightly
to DM and preventing MHCII access,In result :
kinetic studies show that DO acts as competitive
inhibitor of DM
HLA-DO expresion power of inhibitory
13. Overall :
HLA DR-DM-DO Ag peptide not expressed
at the cell surface
HLA DR-DM Ag peptide expressed
at the cell surface
14.
15. In B cells and dendritic cells DO expression is
developmentally regulated :
In Bcells :Initiation of production High expresion
B cells in germinal center Down-regulated
expression
In DCs : DC + Ag = Mature DC Down regulated
expresion
This expression pattern has suggested a role for DO in
promoting tolerance to self-antigens
16.
17. The observations show that HLA-DO is selectively expressed
in B cells and thymic medullary epithelial cells raises the
interesting possibility that this molecule might play a role in
tolerance induction
This idea supported by suppression of autoimmune diabetes
in H-2O transgenic non-obsese diabetic (NOD) mice :
18. Transport of over-expressed HLA-DO genes to NOD
mice CD11c+ DCs Formation of NOD-DO
transgenic mice
Autoimune
diabet Not
developed
Then : NOD-DO Tcells were transferred into NOD-SCID hosts
(lacking T and B cells) Autoimune diabet
developed
CONCLUSION : Overexpressed DO in DCs did not
prevent diabetogenic Tcells from forming but