The major histocompatibility complex (MHC) molecules are membrane-bound glycoproteins that function as specialized antigen-presenting molecules. There are two main classes of MHC molecules - class I and class II. Class I molecules present intracellularly derived antigens to CD8+ T cells, while class II molecules present extracellular antigens engulfed by antigen-presenting cells to CD4+ T cells. Both classes of MHC molecules form stable complexes with peptide ligands within a binding groove and display them on the cell surface for recognition by T-cell receptors.
1. The MHC molecules present peptide antigens to T cells. Class I MHC present intracellular peptides to CD8+ T cells, while class II MHC present extracellular peptides taken up by endocytosis to CD4+ T cells.
2. Antigens are processed through different pathways depending on if they are intracellular or extracellular. Intracellular antigens are degraded by the proteasome and transported into the ER by TAP to bind class I MHC. Extracellular antigens are endocytosed and degraded in lysosomes to bind class II MHC.
3. The peptide-MHC complexes are then transported to the cell surface for recognition by T cell receptors.
L6.0 Immune recognition molecule (MHC,T cell receptor, T cell epitopes, T cel...mohdbakar12
The document discusses immune recognition molecules, focusing on major histocompatibility complex (MHC), T-cell receptors, T-cell epitopes, T-cell markers, B-cell epitopes, and Toll-like receptors. It describes how MHC molecules present antigen peptides to T cells to initiate immune responses. MHC class I molecules present intracellular peptides to CD8+ T cells, while class II molecules present extracellular peptides to CD4+ T cells. MHC molecules bind peptides through their peptide-binding cleft in a polymorphic and promiscuous manner. Very few peptide-MHC complexes are needed to activate antigen-specific T cells.
The major histocompatibility complex (MHC) is a set of surface proteins located on nucleated cells that plays an important role in distinguishing self from non-self and antigen presentation. There are two types of MHC molecules: class I MHC molecules present antigens to cytotoxic T cells on all nucleated cells, while class II MHC molecules present antigens to helper T cells and are found only on antigen-presenting cells. Both MHC classes consist of a transmembrane alpha chain and beta chain that form a peptide-binding groove to load and present antigen peptides. MHC molecules allow the immune system to recognize foreign substances so the body's immune response can be triggered.
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.
The major histocompatibility complex (MHC) is a collection of genes that encode glycoproteins found on the surface of mammalian cells. MHC proteins present antigens and help the immune system distinguish self from nonself. There are two major classes of MHC molecules: class I molecules present antigens to cytotoxic T cells on all nucleated cells, while class II molecules present antigens to helper T cells on antigen-presenting cells that have engulfed foreign antigens. Together, MHC molecules play a key role in cell-cell interaction and initiating adaptive immune responses.
The document discusses the major histocompatibility complex (MHC) and T cell-mediated immunity. It describes how MHC molecules present antigen peptides on the surface of antigen-presenting cells to activate T cells. MHC class I molecules present peptides to CD8 T cells, while MHC class II molecules present peptides to CD4 T cells. Polymorphism in MHC genes allows for a diverse repertoire of MHC molecules between individuals, helping populations resist rapidly mutating pathogens.
The document summarizes key concepts about the major histocompatibility complex (MHC):
1) The MHC was discovered through studies of transplant rejection in mice, which showed that rejection was dependent on the genetics of the donor and recipient strains.
2) MHC molecules present peptide antigens to T cells and play a key role in immune responses, including transplant rejection.
3) MHC molecules are highly polymorphic, with many variants within populations, in order to allow populations to recognize a wide variety of pathogens.
The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 in humans that code for MHC molecules. MHC molecules are divided into three classes: class I molecules are found on almost all nucleated cells and present intracellular peptides; class II molecules are found on antigen-presenting cells and present extracellular peptides; class III molecules are secreted proteins with immune functions like complement components. MHC molecules present peptide fragments to T cells to trigger immune responses and also determine compatibility for organ transplants.
1. The MHC molecules present peptide antigens to T cells. Class I MHC present intracellular peptides to CD8+ T cells, while class II MHC present extracellular peptides taken up by endocytosis to CD4+ T cells.
2. Antigens are processed through different pathways depending on if they are intracellular or extracellular. Intracellular antigens are degraded by the proteasome and transported into the ER by TAP to bind class I MHC. Extracellular antigens are endocytosed and degraded in lysosomes to bind class II MHC.
3. The peptide-MHC complexes are then transported to the cell surface for recognition by T cell receptors.
L6.0 Immune recognition molecule (MHC,T cell receptor, T cell epitopes, T cel...mohdbakar12
The document discusses immune recognition molecules, focusing on major histocompatibility complex (MHC), T-cell receptors, T-cell epitopes, T-cell markers, B-cell epitopes, and Toll-like receptors. It describes how MHC molecules present antigen peptides to T cells to initiate immune responses. MHC class I molecules present intracellular peptides to CD8+ T cells, while class II molecules present extracellular peptides to CD4+ T cells. MHC molecules bind peptides through their peptide-binding cleft in a polymorphic and promiscuous manner. Very few peptide-MHC complexes are needed to activate antigen-specific T cells.
The major histocompatibility complex (MHC) is a set of surface proteins located on nucleated cells that plays an important role in distinguishing self from non-self and antigen presentation. There are two types of MHC molecules: class I MHC molecules present antigens to cytotoxic T cells on all nucleated cells, while class II MHC molecules present antigens to helper T cells and are found only on antigen-presenting cells. Both MHC classes consist of a transmembrane alpha chain and beta chain that form a peptide-binding groove to load and present antigen peptides. MHC molecules allow the immune system to recognize foreign substances so the body's immune response can be triggered.
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.
The major histocompatibility complex (MHC) is a collection of genes that encode glycoproteins found on the surface of mammalian cells. MHC proteins present antigens and help the immune system distinguish self from nonself. There are two major classes of MHC molecules: class I molecules present antigens to cytotoxic T cells on all nucleated cells, while class II molecules present antigens to helper T cells on antigen-presenting cells that have engulfed foreign antigens. Together, MHC molecules play a key role in cell-cell interaction and initiating adaptive immune responses.
The document discusses the major histocompatibility complex (MHC) and T cell-mediated immunity. It describes how MHC molecules present antigen peptides on the surface of antigen-presenting cells to activate T cells. MHC class I molecules present peptides to CD8 T cells, while MHC class II molecules present peptides to CD4 T cells. Polymorphism in MHC genes allows for a diverse repertoire of MHC molecules between individuals, helping populations resist rapidly mutating pathogens.
The document summarizes key concepts about the major histocompatibility complex (MHC):
1) The MHC was discovered through studies of transplant rejection in mice, which showed that rejection was dependent on the genetics of the donor and recipient strains.
2) MHC molecules present peptide antigens to T cells and play a key role in immune responses, including transplant rejection.
3) MHC molecules are highly polymorphic, with many variants within populations, in order to allow populations to recognize a wide variety of pathogens.
The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 in humans that code for MHC molecules. MHC molecules are divided into three classes: class I molecules are found on almost all nucleated cells and present intracellular peptides; class II molecules are found on antigen-presenting cells and present extracellular peptides; class III molecules are secreted proteins with immune functions like complement components. MHC molecules present peptide fragments to T cells to trigger immune responses and also determine compatibility for organ transplants.
The document summarizes key aspects of the major histocompatibility complex (MHC):
1) The MHC was discovered through studies of transplant rejection in inbred mouse strains, which showed that rejection depended on the genetics of the donor and recipient strains.
2) MHC molecules present peptide antigens to T cells and play a crucial role in immune responses, including transplant rejection.
3) MHC molecules are highly polymorphic and polygenic, with multiple variants of each type, which allows populations to recognize a wide variety of pathogens.
Major histocompatility complex (Antigen Presentation to T cells, Autoimmunity...Pradeep Singh Narwat
The document provides an overview of major histocompatibility complex (MHC) molecules, including their history, structure, organization and inheritance, and functions in antigen presentation and immune responses. MHC molecules are membrane-bound glycoproteins that are encoded by genes in the MHC locus and present antigen peptides to T cells to initiate adaptive immune responses against intracellular and extracellular pathogens.
The document summarizes the major histocompatibility complex (MHC), which encodes proteins that play a role in self/non-self discrimination. It describes the structure and function of MHC class I and class II molecules. MHC class I presents endogenous antigens to CD8+ T cells, consisting of an alpha chain, beta-2 microglobulin chain, and a short peptide. MHC class II presents exogenous antigens to CD4+ T cells, consisting of alpha and beta chains that bind longer peptides. Both are membrane-bound glycoproteins that present antigen to T cells via peptide-binding clefts.
The Major Histocompatibility Complex (MHC) refers to a set of genes that code for MHC proteins found on the surfaces of cells. These proteins help the immune system recognize foreign substances by presenting antigen fragments to T cells. There are three main classes of MHC molecules: class I molecules present antigens to CD8+ T cells on nearly all nucleated cells; class II molecules present antigens to CD4+ T cells and are found on antigen-presenting cells; class III molecules encode for other immune system proteins. MHC molecules have a groove that binds peptides for presentation to T cells, allowing the immune system to detect infected or damaged cells.
The immune system refers to a collection of cells, chemicals and processes that function to protect the skin, respiratory passages, intestinal tract and other areas from foreign antigens, such as microbes (organisms such as bacteria, fungi, and parasites), viruses, cancer cells, and toxins.
MHC class I and II molecules are membrane-bound glycoproteins that present antigen peptide fragments to T cells. MHC class I presents endogenous antigens processed via the cytosolic pathway to CD8+ cytotoxic T cells, while MHC class II presents exogenous antigens endocytosed and processed via the endocytic pathway to CD4+ helper T cells. The cytosolic pathway involves proteolytic degradation of antigens in the cytosol and transport of peptides to the ER for assembly with class I MHC. The endocytic pathway involves internalization of exogenous antigens, processing in endosomes, transport of class II MHC to endosomes, and assembly of antigen peptides with class II MHC.
The MHC plays a key role in distinguishing self from nonself. MHC class I molecules present intracellular peptides on the surface of all nucleated cells to be recognized by CD8+ T cells. MHC class II molecules present extracellular peptides captured by antigen presenting cells to be recognized by CD4+ T cells. Together this allows the immune system to detect the presence of foreign pathogens and mount an adaptive immune response while avoiding attacks on self tissues.
Advanced Immunology: Antigen Processing and PresentationHercolanium GDeath
1. Antigens are internalized by antigen presenting cells through endocytosis and degraded within lysosomes into peptide fragments.
2. Peptide fragments from extracellular antigens bind to MHC class II molecules within antigen processing vesicles. The vesicles containing MHC class II-peptide complexes fuse with the cell membrane and present the complexes to CD4+ T cells.
3. Peptide fragments from intracellular antigens are degraded by the proteasome and transported into the endoplasmic reticulum by TAP proteins. The peptides bind to MHC class I molecules and the complexes are presented on the cell surface to CD8+ T cells.
Major Histo compatibility Complex of Genes /certified fixed orthodontic cours...Indian dental academy
The document provides information about the major histocompatibility complex (MHC), a set of genes that encodes antigen-presenting molecules that play a key role in the immune system's response to foreign substances. It discusses how MHC genes were discovered through studies of transplant rejection between inbred mouse strains, and how MHC molecules present peptide antigens to T cells, triggering an immune response. The document also summarizes the structure and function of MHC class I and class II molecules, how they bind peptides, and their extensive polymorphism in human populations, which helps protect against rapidly mutating pathogens.
The document discusses the major histocompatibility complex (MHC), which are surface proteins that play an important role in identifying antigens and presenting them to T cells. It covers the different classes of MHC molecules, their structures, functions in immunity, and examples in humans (HLA) and mice (H-2 complex). MHC molecules present peptide fragments on their surface and interact specifically with T cells through anchor residues on the peptides. They are essential for self/non-self discrimination, defense against infection, and transplantation compatibility.
The document summarizes the major histocompatibility complex (MHC), which screens T cells so that only those capable of binding to MHC molecules are maintained. It discusses MHC restriction, whereby a T cell only recognizes a peptide bound to a particular MHC variant. MHC molecules are highly polymorphic, affecting the range of bound peptides and interactions with T cell receptors. MHC class I presents intracellular peptides to cytotoxic T cells, while MHC class II presents extracellular peptides to T helper cells, leading to different immune responses.
1) Antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells present antigen peptides on their surfaces to activate T cells.
2) APCs capture antigens through phagocytosis, pinocytosis, or receptor-mediated endocytosis and process the antigens into peptides.
3) The peptides are then presented on either MHC class I or MHC class II molecules for recognition by CD8+ or CD4+ T cells respectively, initiating an adaptive immune response.
1) Antigen processing and presentation involves extracellular and intracellular proteins being degraded into peptides and bound to MHC class I or II molecules. These peptide-MHC complexes are expressed on antigen presenting cells and recognized by T cells to initiate an immune response.
2) T cells are activated through recognition of peptide-MHC complexes by their T cell receptors along with co-stimulatory signals. Activated T cells proliferate and differentiate into effector and memory T cells.
3) Effector T cells stimulate immune responses like activating macrophages to kill intracellular pathogens, leading to delayed type hypersensitivity reactions which can cause tissue damage if infection is not resolved.
Major Histocompatibility Complex (MHC) molecules display antigen peptides on the surface of cells to be recognized by T cells. There are two main types of MHC molecules: class I molecules present intracellular peptides to CD8+ T cells on most nucleated cells, while class II molecules present extracellular peptides to CD4+ T cells on antigen-presenting cells like dendritic cells and macrophages. MHC molecules bind peptides promiscuously but polymorphisms among individuals influence peptide binding. Dendritic cells are especially effective at antigen capture and presentation to initiate primary T cell responses.
The major histocompatibility complex (MHC) is a cluster of genes located on chromosome 6 in humans that encodes proteins involved in the immune system's recognition of self and non-self. The MHC includes class I, II, and III genes. Class I genes produce molecules that present intracellular peptides to cytotoxic T cells, while class II genes produce molecules that present extracellular peptides to helper T cells. Antigens are processed through either the cytosolic or endocytic pathway and bound to MHC molecules to be presented at the cell surface for recognition by T cells.
The document discusses an anti-radiation vaccine technology involving Dmitri Popov, Maliev Slava, and Jeffrey Jones. It summarizes the roles of white blood cells (leukocytes) and their organelles (lysosomes) in presenting antigen peptides through MHC class I and II molecules to activate immune responses. Specifically, it describes how lysosome-associated membrane proteins (LAMPs) are involved in antigen processing and presentation to T cells to stimulate immune defenses against radiation and infectious agents.
Major Histocompatibility Complex (MHC) molecules present peptide antigens to T cells and are highly polymorphic. MHC molecules are classified into three main classes - Class I molecules present intracellular peptides to CD8+ T cells, Class II present extracellular peptides to CD4+ T cells, and Class III genes encode complement proteins. MHC molecules have a peptide-binding groove that binds short peptides for presentation to T cells. MHC polymorphism generates a diverse repertoire of molecules that can present a wide variety of peptides and mount immune responses against pathogens.
Class I and class II MHC molecules bind antigenic peptides derived from degraded antigens. MHC molecules present antigen peptides to T cells but do not have the fine specificity of antibodies or T cell receptors. The distal regions of MHC molecules display allelic variation that results in different antigen-binding clefts with varying specificities. For an antigen to be recognized by T cells, it must be degraded into peptides that form complexes with class I or class II MHC molecules on the cell surface in a process called antigen processing and presentation.
Immunoelectrophoresis is a technique used in clinical laboratories to detect the presence or absence of proteins in serum. It works by electrophoresing the serum sample to separate its components, then exposing it to antisera specific to different proteins. Lines will form where antigens and antibodies interact, identifying the proteins present. It is useful for determining if a patient produces abnormal amounts of certain proteins, as seen in immunodeficiency diseases or multiple myeloma. While qualitative, it can detect large departures from normal protein levels. A related quantitative technique, rocket electrophoresis, measures antigen levels based on the height of precipitate "rockets" formed during electrophoresis.
Southern blotting is a technique used to detect specific DNA sequences within genomes. It involves digesting genomic DNA with restriction enzymes, separating the fragments via gel electrophoresis, transferring the DNA to a membrane, and using a radioactive probe to hybridize to complementary sequences on the membrane. This allows researchers to visualize specific DNA fragments and analyze their presence, absence, size, and any alterations like mutations.
The document summarizes key aspects of the major histocompatibility complex (MHC):
1) The MHC was discovered through studies of transplant rejection in inbred mouse strains, which showed that rejection depended on the genetics of the donor and recipient strains.
2) MHC molecules present peptide antigens to T cells and play a crucial role in immune responses, including transplant rejection.
3) MHC molecules are highly polymorphic and polygenic, with multiple variants of each type, which allows populations to recognize a wide variety of pathogens.
Major histocompatility complex (Antigen Presentation to T cells, Autoimmunity...Pradeep Singh Narwat
The document provides an overview of major histocompatibility complex (MHC) molecules, including their history, structure, organization and inheritance, and functions in antigen presentation and immune responses. MHC molecules are membrane-bound glycoproteins that are encoded by genes in the MHC locus and present antigen peptides to T cells to initiate adaptive immune responses against intracellular and extracellular pathogens.
The document summarizes the major histocompatibility complex (MHC), which encodes proteins that play a role in self/non-self discrimination. It describes the structure and function of MHC class I and class II molecules. MHC class I presents endogenous antigens to CD8+ T cells, consisting of an alpha chain, beta-2 microglobulin chain, and a short peptide. MHC class II presents exogenous antigens to CD4+ T cells, consisting of alpha and beta chains that bind longer peptides. Both are membrane-bound glycoproteins that present antigen to T cells via peptide-binding clefts.
The Major Histocompatibility Complex (MHC) refers to a set of genes that code for MHC proteins found on the surfaces of cells. These proteins help the immune system recognize foreign substances by presenting antigen fragments to T cells. There are three main classes of MHC molecules: class I molecules present antigens to CD8+ T cells on nearly all nucleated cells; class II molecules present antigens to CD4+ T cells and are found on antigen-presenting cells; class III molecules encode for other immune system proteins. MHC molecules have a groove that binds peptides for presentation to T cells, allowing the immune system to detect infected or damaged cells.
The immune system refers to a collection of cells, chemicals and processes that function to protect the skin, respiratory passages, intestinal tract and other areas from foreign antigens, such as microbes (organisms such as bacteria, fungi, and parasites), viruses, cancer cells, and toxins.
MHC class I and II molecules are membrane-bound glycoproteins that present antigen peptide fragments to T cells. MHC class I presents endogenous antigens processed via the cytosolic pathway to CD8+ cytotoxic T cells, while MHC class II presents exogenous antigens endocytosed and processed via the endocytic pathway to CD4+ helper T cells. The cytosolic pathway involves proteolytic degradation of antigens in the cytosol and transport of peptides to the ER for assembly with class I MHC. The endocytic pathway involves internalization of exogenous antigens, processing in endosomes, transport of class II MHC to endosomes, and assembly of antigen peptides with class II MHC.
The MHC plays a key role in distinguishing self from nonself. MHC class I molecules present intracellular peptides on the surface of all nucleated cells to be recognized by CD8+ T cells. MHC class II molecules present extracellular peptides captured by antigen presenting cells to be recognized by CD4+ T cells. Together this allows the immune system to detect the presence of foreign pathogens and mount an adaptive immune response while avoiding attacks on self tissues.
Advanced Immunology: Antigen Processing and PresentationHercolanium GDeath
1. Antigens are internalized by antigen presenting cells through endocytosis and degraded within lysosomes into peptide fragments.
2. Peptide fragments from extracellular antigens bind to MHC class II molecules within antigen processing vesicles. The vesicles containing MHC class II-peptide complexes fuse with the cell membrane and present the complexes to CD4+ T cells.
3. Peptide fragments from intracellular antigens are degraded by the proteasome and transported into the endoplasmic reticulum by TAP proteins. The peptides bind to MHC class I molecules and the complexes are presented on the cell surface to CD8+ T cells.
Major Histo compatibility Complex of Genes /certified fixed orthodontic cours...Indian dental academy
The document provides information about the major histocompatibility complex (MHC), a set of genes that encodes antigen-presenting molecules that play a key role in the immune system's response to foreign substances. It discusses how MHC genes were discovered through studies of transplant rejection between inbred mouse strains, and how MHC molecules present peptide antigens to T cells, triggering an immune response. The document also summarizes the structure and function of MHC class I and class II molecules, how they bind peptides, and their extensive polymorphism in human populations, which helps protect against rapidly mutating pathogens.
The document discusses the major histocompatibility complex (MHC), which are surface proteins that play an important role in identifying antigens and presenting them to T cells. It covers the different classes of MHC molecules, their structures, functions in immunity, and examples in humans (HLA) and mice (H-2 complex). MHC molecules present peptide fragments on their surface and interact specifically with T cells through anchor residues on the peptides. They are essential for self/non-self discrimination, defense against infection, and transplantation compatibility.
The document summarizes the major histocompatibility complex (MHC), which screens T cells so that only those capable of binding to MHC molecules are maintained. It discusses MHC restriction, whereby a T cell only recognizes a peptide bound to a particular MHC variant. MHC molecules are highly polymorphic, affecting the range of bound peptides and interactions with T cell receptors. MHC class I presents intracellular peptides to cytotoxic T cells, while MHC class II presents extracellular peptides to T helper cells, leading to different immune responses.
1) Antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells present antigen peptides on their surfaces to activate T cells.
2) APCs capture antigens through phagocytosis, pinocytosis, or receptor-mediated endocytosis and process the antigens into peptides.
3) The peptides are then presented on either MHC class I or MHC class II molecules for recognition by CD8+ or CD4+ T cells respectively, initiating an adaptive immune response.
1) Antigen processing and presentation involves extracellular and intracellular proteins being degraded into peptides and bound to MHC class I or II molecules. These peptide-MHC complexes are expressed on antigen presenting cells and recognized by T cells to initiate an immune response.
2) T cells are activated through recognition of peptide-MHC complexes by their T cell receptors along with co-stimulatory signals. Activated T cells proliferate and differentiate into effector and memory T cells.
3) Effector T cells stimulate immune responses like activating macrophages to kill intracellular pathogens, leading to delayed type hypersensitivity reactions which can cause tissue damage if infection is not resolved.
Major Histocompatibility Complex (MHC) molecules display antigen peptides on the surface of cells to be recognized by T cells. There are two main types of MHC molecules: class I molecules present intracellular peptides to CD8+ T cells on most nucleated cells, while class II molecules present extracellular peptides to CD4+ T cells on antigen-presenting cells like dendritic cells and macrophages. MHC molecules bind peptides promiscuously but polymorphisms among individuals influence peptide binding. Dendritic cells are especially effective at antigen capture and presentation to initiate primary T cell responses.
The major histocompatibility complex (MHC) is a cluster of genes located on chromosome 6 in humans that encodes proteins involved in the immune system's recognition of self and non-self. The MHC includes class I, II, and III genes. Class I genes produce molecules that present intracellular peptides to cytotoxic T cells, while class II genes produce molecules that present extracellular peptides to helper T cells. Antigens are processed through either the cytosolic or endocytic pathway and bound to MHC molecules to be presented at the cell surface for recognition by T cells.
The document discusses an anti-radiation vaccine technology involving Dmitri Popov, Maliev Slava, and Jeffrey Jones. It summarizes the roles of white blood cells (leukocytes) and their organelles (lysosomes) in presenting antigen peptides through MHC class I and II molecules to activate immune responses. Specifically, it describes how lysosome-associated membrane proteins (LAMPs) are involved in antigen processing and presentation to T cells to stimulate immune defenses against radiation and infectious agents.
Major Histocompatibility Complex (MHC) molecules present peptide antigens to T cells and are highly polymorphic. MHC molecules are classified into three main classes - Class I molecules present intracellular peptides to CD8+ T cells, Class II present extracellular peptides to CD4+ T cells, and Class III genes encode complement proteins. MHC molecules have a peptide-binding groove that binds short peptides for presentation to T cells. MHC polymorphism generates a diverse repertoire of molecules that can present a wide variety of peptides and mount immune responses against pathogens.
Class I and class II MHC molecules bind antigenic peptides derived from degraded antigens. MHC molecules present antigen peptides to T cells but do not have the fine specificity of antibodies or T cell receptors. The distal regions of MHC molecules display allelic variation that results in different antigen-binding clefts with varying specificities. For an antigen to be recognized by T cells, it must be degraded into peptides that form complexes with class I or class II MHC molecules on the cell surface in a process called antigen processing and presentation.
Immunoelectrophoresis is a technique used in clinical laboratories to detect the presence or absence of proteins in serum. It works by electrophoresing the serum sample to separate its components, then exposing it to antisera specific to different proteins. Lines will form where antigens and antibodies interact, identifying the proteins present. It is useful for determining if a patient produces abnormal amounts of certain proteins, as seen in immunodeficiency diseases or multiple myeloma. While qualitative, it can detect large departures from normal protein levels. A related quantitative technique, rocket electrophoresis, measures antigen levels based on the height of precipitate "rockets" formed during electrophoresis.
Southern blotting is a technique used to detect specific DNA sequences within genomes. It involves digesting genomic DNA with restriction enzymes, separating the fragments via gel electrophoresis, transferring the DNA to a membrane, and using a radioactive probe to hybridize to complementary sequences on the membrane. This allows researchers to visualize specific DNA fragments and analyze their presence, absence, size, and any alterations like mutations.
Blotting techniques allow the transfer of DNA, RNA, or proteins from a gel to a membrane for detection. Southern blotting detects DNA using separation, transfer, and hybridization with a DNA probe. Northern blotting detects RNA and was developed at Stanford University. Western blotting identifies specific proteins by separating them using SDS-PAGE gel electrophoresis, transferring them to a membrane, and detecting them using labeled antibodies in an antigen-antibody reaction. These techniques have applications in gene discovery, mapping, diagnostics, and more.
Vaccines are produced through a multi-step process involving growing pathogens under controlled conditions, isolating and purifying antigens, and formulating the vaccine. Live attenuated vaccines are made by weakening pathogens through special growth conditions. Inactivated vaccines are produced by killing pathogens through chemicals or heat. Recombinant vaccines involve expressing pathogen genes in host cells to produce antigens. Strict quality controls ensure vaccine safety and efficacy.
The spleen filters blood and traps blood-borne pathogens and antigens. It contains red pulp with blood sinusoids and macrophages that remove old red blood cells. The white pulp contains follicles with B cells and periarteriolar lymphoid sheaths with T cells that mount adaptive immune responses. The marginal zone contains specialized macrophages and B cells that are the first line of defense against blood-borne pathogens. The spleen helps fight systemic infections.
Radioimmunoassays (RIA) use radioactive labels to measure hormone and protein concentrations in body fluids. In 1960, Berson and Yalow developed RIA to quantify insulin levels, making it possible to detect substances that were previously unmeasurable. RIA relies on competitive binding between labeled and unlabeled antigens or antibodies, and separation of bound from unbound reagents, typically using a solid support. The amount of radioactivity bound indicates the concentration of the target substance in the test sample.
Probes are short nucleic acid sequences used to detect target nucleic acids. They are chemically synthesized with labels like fluorescent dyes or isotopic labels. Probes can be labeled during or after synthesis through techniques like nick translation, random priming, or PCR. Labeled probes allow visualization of hybridized target nucleic acids and are used in techniques like Southern blotting and fluorescence in situ hybridization.
Secondary lymphoid organs initiate immune responses by allowing lymphocytes and antigen presenting cells to interact. These organs include lymph nodes, the spleen, tonsils, and mucosa-associated lymphoid tissue found in the digestive and respiratory tracts. They are connected by both the circulatory and lymphatic systems which transport immune cells and antigens between tissues and lymphoid organs. Within secondary lymphoid organs, T cell and B cell zones allow interactions that initiate adaptive immune responses to infections and foreign substances that enter the body.
The bone marrow and thymus are the two primary lymphoid organs responsible for immune cell development. The bone marrow supports the development of all blood cells including B lymphocytes. It also contains hematopoietic stem cells that give rise to immune cells. However, T lymphocytes must leave the bone marrow and travel to the thymus to complete their development, where they undergo selection processes to ensure they do not attack the body's own tissues.
Phagocytosis is a key defense mechanism of the innate immune system. Phagocytic cells such as macrophages recognize pathogens through pattern recognition receptors that bind to pathogen-associated molecular patterns. Opsonins such as antibodies and complement proteins enhance phagocytosis by binding to pathogens and serving as ligands for phagocyte opsonin receptors. Internalized pathogens are killed through the fusion of phagosomes with lysosomes and the release of reactive oxygen species and antimicrobial peptides. Phagocytosis also clears cellular debris and aged or damaged cells.
1) Microbes trigger their uptake and killing by immune cells and induce innate immune responses through pattern recognition receptors (PRRs).
2) PRRs recognize pathogen-associated molecular patterns and damage-associated molecular patterns, activating signaling pathways that induce antimicrobial proteins.
3) The major PRR families - Toll-like receptors, C-type lectin receptors, RIG-I-like receptors, and Nod-like receptors - recognize pathogens and trigger immune responses through pathways that promote phagocytosis and induce interferons, cytokines, chemokines and other effectors.
The lymph node is a highly specialized secondary lymphoid organ that filters lymph and mounts immune responses. It contains distinct microenvironments - the cortex containing B cells, follicles and macrophages; the paracortex populated by T cells and dendritic cells; and the medulla where lymphocytes exit and plasma cells reside. Antigen and immune cells enter via afferent lymphatics and blood vessels, with naïve lymphocytes entering through high endothelial venules. In germinal centers, B cells proliferate, mutate and differentiate into plasma cells under guidance from follicular dendritic and T cells. Memory T and B cells are also generated to provide long-term protection.
The immune system has evolved to protect organisms from pathogens. It consists of a complex network of cells, molecules, and pathways. The immune system recognizes and destroys pathogens through both humoral immunity involving antibodies, and cellular immunity mediated by T cells. Immunity can be active, induced by vaccination or infection, providing long-term protection, or passive, involving transfer of antibodies between individuals.
Natural killer (NK) cells are a type of lymphocyte that helps initiate innate immune responses against pathogens and damaged or cancerous cells. They recognize and target cells with reduced expression of self-MHC proteins and release cytokines and cytotoxic proteins to induce apoptosis. NK cells provide rapid early responses and help activate and regulate the adaptive immune system through cytokine signaling and antigen presentation by dendritic cells.
The document summarizes inflammatory responses and their role in innate immunity. When barriers like the skin are damaged, resident cells release signals that trigger inflammation - characterized by redness, swelling, heat and pain. This response recruits leukocytes and tries to resolve infection or damage through pathogen clearance and healing. However, chronic inflammation from persistent triggers can lead to long-term issues like arthritis or disease.
Hypersensitivity reactions are immune disorders caused by an inappropriate response to antigens that are not pathogens. There are four main types of hypersensitivity reactions: Type I are rapid IgE-mediated allergic reactions; Type II involve IgG/IgM antibodies binding to cells and recruiting complement; Type III occur when immune complexes are not cleared and deposit in tissues, inducing inflammation; Type IV are delayed T cell-mediated reactions like contact dermatitis.
Autoimmunity is caused by a failure of tolerance mechanisms that normally protect the body from self-reactive lymphocytes. This leads to destruction of self tissues by autoantibodies or self-reactive T cells, causing diseases like Hashimoto's thyroiditis or rheumatoid arthritis. Autoimmune diseases can affect single organs or multiple systems, and are characterized by inflammatory responses and tissue damage directed against particular antigens.
The document discusses the structure of antibodies. It describes how antibodies are made up of two light chains and two heavy chains arranged in a Y-shape. Each chain contains constant and variable domains. The variable domains form the antigen binding sites and contain hypervariable regions that bind antigens. The constant domains mediate different immune functions depending on the class of heavy chain. Papain and pepsin digestion were used to determine that the Fab regions contain the antigen binding sites while the Fc region mediates downstream immune functions. Together, these experiments elucidated the basic four-chain structure of antibodies.
The complement system consists of over 30 proteins that work together to eliminate pathogens from the blood and tissues. There are three pathways of complement activation - the classical, lectin, and alternative pathways. They all converge on generating C3 and C5 convertases that cleave C3 and C5, producing fragments that opsonize pathogens, induce inflammation, and form the membrane attack complex to kill pathogens. The classical pathway is initiated by antibody binding, while the lectin pathway uses mannose-binding lectin and ficolins that recognize carbohydrates on microbes. Both result in the same C3 and C5 convertases. The alternative pathway is antibody-independent and activates via C3 hydrolysis.
The innate immune system provides the first line of defense against pathogens. It includes physical barriers like the skin and mucous membranes, as well as chemical barriers containing antimicrobial peptides and proteins. These barriers prevent pathogen entry, but some pathogens can breach them. The innate system then mounts cellular responses through phagocytosis and inflammation. Antimicrobial peptides and proteins secreted by epithelial barriers also help kill pathogens. Together, these nonspecific defenses provide rapid initial protection against infection.
How to Make a Field Mandatory in Odoo 17Celine George
In Odoo, making a field required can be done through both Python code and XML views. When you set the required attribute to True in Python code, it makes the field required across all views where it's used. Conversely, when you set the required attribute in XML views, it makes the field required only in the context of that particular view.
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Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
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A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
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Odoo 17 CRM allows us to track why we lose sales opportunities with "Lost Reasons." This helps analyze our sales process and identify areas for improvement. Here's how to configure lost reasons in Odoo 17 CRM
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
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9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
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Answers about how you can do more with Walmart!"
2. • Both T and B cells use surface molecules to
recognize antigen; they accomplish this in very
different ways.
• Antibodies or B-cell receptors can recognize an
antigen alone;
• T-cell receptors only recognize pieces of antigen
that are positioned on the surface of other cells.
• These antigen pieces are held within the binding
groove of a cell surface protein called the major
histocompatibility complex (MHC) molecule,
encoded by a cluster of genes collectively called
the MHC locus.
3. • These fragments are generated inside the cell
following antigen digestion, and the complex of
the antigenic peptide plus MHC molecule then
appears on the cell surface.
• MHC molecules thus act as a cell surface vessel
for holding and displaying fragments of antigen
so that approaching T cells can engage with this
molecular complex via their T-cell receptors.
4. • The fact that the genes in this (MHC) region
encode proteins that determine whether a
tissue transplanted between two individuals
will be accepted or rejected, gave MHC its
name.
• The pioneering work of Benacerraf, Dausset,
and Snell helped to characterize the functions
controlled by the MHC, specifically, organ
transplant fate and the immune responses to
antigen, resulting in the 1980 Nobel Prize in
Medicine and Physiology for the trio.
5. • Follow-up studies by Rolf Zinkernagel and
Peter Doherty illustrated that the proteins
encoded by these genes play a seminal role in
adaptive immunity by showing that T cells
recognize MHC proteins as well as antigen.
• Structural studies done by Don Wiley and
others showed that different MHC proteins
bind and present different antigen fragments.
6. • There are many alleles of most MHC genes,
• the specific alleles one inherits play a
significant role in susceptibility to disease,
including the development of autoimmunity.
• Autoimmunity is the system of immune
responses of an organism against its own
healthy cells and tissues.
• Any disease that results from such an
aberrant immune response is termed
an autoimmune disease.
7. • There are two main classes of MHC
molecules:
– Class I and Class II.
• These two molecules are very similar in their
final quaternary structure, although they
differ in how they create these shapes.
• They also differ
– in terms of which cells express them and
– in the source of the antigens they present to T
cells.
8. • Class I molecules
– are present on all nucleated cells in the body
– specialize in presenting antigens that originate from
the cytosol, such as viral proteins.
• MHC class I molecule presents the antigenic
peptide to CD8+ T cells, which recognize and kill
cells expressing such intracellular antigens.
9. • Class II MHC molecules, in contrast,
– are expressed almost exclusively on a subset of
leukocytes called antigen-presenting cells (APCs)
– specialize in presenting antigens from extracellular
spaces that have been engulfed by these cells,
such as fungi and extracellular bacteria.
• MHC class II molecule presents the antigenic
peptide to CD4+ T cells, once expressed on the
cell surface
• CD4+ T cells then become activated and go on
to stimulate immunity directed primarily
toward destroying extracellular invaders.
10. The Structure and Function of MHC Molecules
• Class I and class II MHC molecules are
membrane-bound glycoproteins that are
closely related in both structure and function
• These function as highly specialized antigen-
presenting molecules with grooves.
• These grooves
– form unusually stable complexes with peptide
ligands, and
– Display them on the cell surface for recognition by
T cells via T-cell receptor (TCR) engagement.
11. • Class III MHC molecules, in contrast,
– are a group of unrelated proteins
– do not share structural similarity or function with
class I and II molecules
– although many of them do participate in other
aspects of the immune response.
12. Class I Molecules Have a Glycoprotein Heavy Chain and
a Small Protein Light Chain
• Two polypeptides assemble to form a single class I
MHC molecule:
– a 45-kilodalton (kDa) α chain and
– a 12-kDa β2-microglobulin molecule.
• The α chain is organized into
– three external domains (α1, α2, and α3), each
approximately 90 amino acids long;
– a transmembrane domain of about 25 hydrophobic
amino acids followed by a short stretch of charged
(hydrophilic) amino acids;
– and a cytoplasmic anchor segment of 30 amino acids.
13. • Its companion, β2-microglobulin,
– is similar in size and organization to the α3
domain.
– does not contain a transmembrane region and
– is non-covalently bound to the MHC class I chain.
• Sequence data reveal strong homology
between the α3 domain of MHC class I, β2-
microglobulin, and the constant-region
domains found in immunoglobulins.
14.
15.
16. • The α1 and α2 domains interact to form a
platform of eight antiparallel β strands spanned
by two long α–helical regions.
• The structure forms a deep groove, or cleft ,
with the long α helices as sides and the β strands
of the sheet as the bottom.
• This peptide-binding groove
– is located on the top surface of the class I MHC
molecule, and
– it is large enough to bind a peptide of 8 to 10 amino
acids.
17. • The α3 domain and β2-microglobulin are organized into
two β pleated sheets each formed by antiparallel
strands of amino acids, known as the immunoglobulin
fold.
• So class I MHC molecules and β2-microglobulin are
classified as members of the immunoglobulin
superfamily .
• The α3 domain appears to be highly conserved among
class I MHC molecules and contains a sequence that
interacts strongly with the CD8 cell surface molecule
found on TC cells.
• All three molecules (class I α chain, β2-microglobulin,
and a peptide) are essential to the proper folding and
expression of the MHC-peptide complex on the cell
surface.
18. Class II Molecules Have Two Non-Identical
Glycoprotein Chains
• Class II MHC molecules contain two different
polypeptide chains which associate by non
covalent interactions
– a 33-kDa α chain and
– a 28-kDa β chain
• Like class I chains, class II MHC molecules
– are membrane bound glycoproteins that contain
external domains,
– a transmembrane segment, and
– a cytoplasmic anchor segment.
• Each chain in a class II molecule contains two
external domains: α1 and α2 domains in one
chain and β1 and β2 domains in the other.
19.
20. • The membrane-proximal α2 and β2 domains
bear sequence similarity to the
immunoglobulin-fold structure, hence, are
also classified in the immunoglobulin
superfamily.
• The α1 and β1 domains form the peptide-
binding groove for processed antigen .
• Although similar to the peptide-binding
groove of MHC class I, this groove is formed
by the association of two separate chains.
21. • Despite the structural similarity between these
two classes of molecule, the two structures are
encoded quite differentially
• The final quaternary structure is similar and
retains the same overall function: the ability to
bind antigen and present it to T cells.
• The peptide-binding groove of class II molecules,
like that found in class I molecules, is composed
of a floor of eight antiparallel β strands and sides
of antiparallel α helices, where peptides typically
ranging from 13 to 18 amino acids can bind.
22. • The class II molecule lacks the conserved
residues in the class I molecule that bind to
the terminal amino acids of short antigenic
peptides, and therefore forms more of an
open pocket.
• In this way, class I presents more of a socket-
like opening, whereas class II possesses an
open-ended groove.
23.
24.
25.
26.
27. Class I and II Molecules Exhibit Polymorphism in
the Region That Binds to Peptides
• Several hundred different allelic variants of class I
and II MHC molecules have been identified in
humans.
• Any one individual, however, expresses only a
small number of these molecules—up to six
different class I molecules and 12 or more
different class II molecules.
• This limited number of MHC molecules must be
able to present an enormous array of different
antigenic peptides to T cells, permitting the
immune system to respond specifically to a wide
variety of antigenic challenges.
28. • A given MHC molecule can bind numerous
different peptides, and some peptides can
bind to several different MHC molecules.
• Because of this broad specificity, the binding
between a peptide and an MHC molecule is
often referred to as “promiscuous.”
• Thus, peptide binding by class I and II
molecules does not exhibit the fine specificity
characteristic of antigen binding by antibodies
and T-cell receptors.
29. General Organization and Inheritance of the MHC
• MHC molecules must be able to bind a wide variety of
antigens, and they must do so with relatively strong
affinity.
• They meet this challenge using very different strategies.
• MHC molecules have opted for a combination of
peptide binding promiscuity and the expression of
several different MHC molecules on every cell
• Using this clever combined strategy, the immune
system has evolved a way of maximizing the chances
that many different regions, or epitopes, of an antigen
will be recognized.
30. • Every vertebrate species studied to date possesses
the tightly linked cluster of genes that constitute
the MHC.
• MHC gene cluster studies originated when it was
found that the rejection of foreign tissue
transplanted between individuals in a species was
the result of an immune response mounted
against cell surface molecules, now called
histocompatibility antigens.
• In the mid-1930s, Peter Gorer, who was using
inbred strains of mice to identify blood-group
antigens, identified four groups of genes that
encode blood-cell antigens.
31. • He designated these I - IV.
• Work carried out in the 1940s and 1950s by
Gorer and George Snell established that antigens
encoded by the genes in the group designated as
II took part in the rejection of transplanted
tumors and other tissue.
• Snell called these histocompatibility genes; their
current designation as histocompatibility-2 (H-2,
or MHC) genes in the mouse was in reference to
Gorer’s original group II blood-cell antigens.
32. The MHC Locus Encodes Three Major Classes of
Molecules
• The major histocompatibility complex is a
collection of genes arrayed within a long
continuous stretch of DNA on
• chromosome 6 in humans
• chromosome 17 in mice;
• These regions have been most studied in these
two species
• The MHC is referred to as the
– human leukocyte antigen (HLA) complex in humans
– H-2 complex in mice
33. • The arrangement of genes is somewhat different in the two
species
• In both cases (humans and mice), the MHC genes are
organized into regions encoding three classes of molecules:
– Class I MHC genes encode glycoproteins expressed on the
surface of nearly all nucleated cells; the major function of the
class I gene products is presentation of endogenous peptide
antigens to CD8 T cells.
– Class II MHC genes encode glycoproteins expressed
predominantly on APCs (macrophages, dendritic cells, and B
cells), where they primarily present exogenous antigenic
peptides to CD4 T cells.
– Class III MHC genes encode several different proteins, some
with immune functions, including
• components of the complement system (C4, C2, and factor B) and
• molecules involved in inflammation (inflammatory cytokines, including
the two tumor necrosis factor proteins, TNF- α and TNF-β, also called
lymphotoxin α )
36. • Class I MHC molecules were the first
discovered and are expressed in the widest
range of cell types.
• In mouse, the region encoding Class I MHC
molecules is noncontinuous, interrupted by
the class II and III regions but not in humans
• There are two chains to the MHC class I
molecule: the more variable and antigen-
binding α chain and the common β-2-
microglobulin chain.
37. • The α chain molecules are encoded
–by the K and D regions in mice, with an
additional L region found in some strains,
and
–by the A, B, and C loci in humans.
• β 2-microglobulin is encoded by a gene
outside the MHC.
• Collectively, these are referred to as classical
class I molecules; all posses the functional
capability of presenting protein fragments of
antigen to T cells.
38. • Additional genes or groups of genes within the class I
region of both mouse and human encode nonclassical
class I molecules that are
– expressed only in specific cell types and
– have more specialized functions.
• Some appear to play a role in self/nonself
discrimination. One example is the class I HLA-G
molecule.
• These are present on fetal cells at the maternal-fetal
interface and inhibit rejection by maternal CD8 T cells
by protecting the fetus from identification as foreign,
which may occur when paternally derived antigens
begin to appear on the developing fetus.
39. • Class II MHC molecules are encoded by the
– IA and IE regions in mice
– DP, DQ, and DR regions in humans.
• The terminology is somewhat confusing, since
the D region in mice encodes class I MHC
molecules, whereas DP, DQ, and DR in humans
refers to class II genes and molecules.
40. • The class II region of the MHC locus encodes both the α
chain and the β chain of a particular class II MHC molecule,
and in some cases multiple genes are present for either or
both chains.
• For example, individuals can inherit up to four functional
DR β-chain genes, and all of these are expressed
simultaneously in the cell.
• This allows any DR α -chain gene product to pair with any
DR β chain product.
• Since the antigen-binding groove of class II is formed by a
combination of the α and β chains, this creates several
unique antigen-presenting DR molecules on the cell.
41. • As with the class I loci, additional nonclassical class II
molecules with specialized immune functions are
encoded within this region.
• For instance, human non classical class II genes
designated DM and DO have been identified.
• The DM genes encode a class II–like molecule (HLA-
DM) that
– facilitates the loading of antigenic peptides into class II
MHC molecules.
• Class II DO molecules, expressed only in the thymus
and on mature B cells,
– serve as regulators of class II antigen processing.
42. • Class III MHC region encodes several molecules
that are critical to immune function but have
little in common with class I or II molecules.
• Class III products include
– the complement components C4, C2, and factor B
– several inflammatory cytokines, including the two
tumor necrosis factor proteins (TNF- α and
Lymphotoxin- α [TNF-β]).
43. • Allelic variants of some of these class III MHC
gene products have been linked to certain
diseases.
• For example, polymorphisms within the TNF-α
gene, which encodes a cytokine involved in
many immune processes, have been linked to
– susceptibility to certain infectious diseases and
– some forms of autoimmunity, including Crohn’s
disease and rheumatic arthritis.
44.
45. Expression of MHC Class II Molecules Is
Primarily Restricted to Antigen-Presenting
Cells
• MHC class II molecules are found on a much more
restricted set of cells than class I MHC molecules
• Cells that display peptides associated with class II
MHC molecules and present these peptides to CD4
TH cells, are called antigen-presenting cells
(APCs), and these cells are primarily certain types
of leukocytes.
• APCs are specialized for their ability to alert the
immune system to the presence of an invader and
drive the activation of T cell responses.
46. • Among the various APCs, marked differences in
the level of MHC class II expression have been
observed.
• In some cases, class II expression depends on the
cell’s differentiation stage or level of activation
(such as in macrophages).
• APC activation usually occurs following
interaction with a pathogen and/or via cytokine
signaling, which then induces significant
increases in MHC class II expression.
47. • A variety of cells can function as bonafide APCs.
• Their distinguishing feature is their ability to
express class II MHC molecules and to deliver a
costimulatory, or second activating signal, to T
cells.
• Three cell types are known to have these
characteristics and are thus often referred to as
professional antigen-presenting cells (pAPCs):
– dendritic cells, macrophages, and B lymphocytes.
• These cells differ from one another
– in their mechanisms of antigen uptake,
– in whether they constitutively express class II MHC
molecules, and
– in their costimulatory activity, as follows:
48. – Dendritic cells are generally viewed as the most
effective of the APCs as they constitutively express a
high levels of class II MHC molecules and have inherent
costimulatory activity, they can activate naïve TH cells.
– Macrophages must be activated (e.g., via TLR signaling)
before they express class II MHC molecules or
costimulatory membrane molecules such as CD80/86.
– B cells constitutively express class II MHC molecules and
posses antigen-specific surface receptors, making them
particularly efficient at capturing and presenting their
cognate antigen.
– However, they must be activated by, for example,
antigen, cytokines, or pathogen-associated molecular
patterns (PAMPs), before they express the
costimulatory molecules required for activating naïve TH
cells.
49. • Several other cell types, classified as nonprofessional
APCs, can be induced to express class II MHC
molecules and/or a costimulatory signal under certain
conditions.
• E.g.
– Fibroblasts (skin),
– glial cells(brain),
– pancreatic beta cells,
– thymic epithelial cells,
– thyroid epithelial cells,
– vascular endothelial cells.
• These cells can be deputized for professional antigen
presentation for short periods and in particular
situations, such as during a sustained inflammatory
response.
50. S U M M A R Y
• The major histocompatibility complex (MHC) encodes class I
and II molecules, which function in antigen presentation to T
cells, and class III molecules, which have diverse functions.
• Class I MHC molecules consist of a large glycoprotein α
chain encoded by an MHC gene, and β2-microglobulin, a
protein with a single domain that is encoded elsewhere.
• Class II MHC molecules are composed of two noncovalently
associated glycoproteins, the α and β chains, encoded by
separate MHC genes.
• MHC genes are tightly linked and generally inherited as a
unit from parents; these linked units are called haplotypes.
51. • MHC genes are polymorphic (many alleles exist for
each gene in the population), polygenic (several
different MHC genes exist in an individual), and
codominantly expressed (both maternal and paternal
copies).
• MHC alleles influence the fragments of antigen that are
presented to the immune system, thereby influencing
susceptibility to a number of diseases.
• Class I molecules are expressed on most nucleated
cells; class II molecules are restricted to B cells,
macrophages, and dendritic cells (pAPCs).
52. • In most cases, class I molecules present processed
endogenous antigen to CD8 TC cells and class II
molecules present processed exogenous antigen to CD4
TH cells.
• Endogenous antigens are degraded into peptides within
the cytosol by proteasomes, assemble with class I
molecules in the RER, and are presented on the
membrane to CD8 TC cells. This is the endogenous
processing and presentation pathway.
• Exogenous antigens are internalized and degraded
within the acidic endocytic compartments and
subsequently combine with class II molecules for
presentation to CD4 TH cells. This is the exogenous
processing and presentation pathway.
53. • Peptide binding to class II molecules involves
replacing a fragment of invariant chain in the
binding groove by a process catalyzed by
nonclassical MHC molecule HLA-DM.
• In some cases, exogenous antigens in certain cell
types (mainly DCs) can gain access to class I
presentation pathways in a process called cross-
presentation.
• Presentation of nonpeptide (lipid and lipid-
linked) antigens derived from pathogens involves
the nonclassical class I–like CD1 molecules.
54.
55. • Fibroblasts skin cells within the dermis layer of skin which
are responsible for generating connective tissue and
allowing the skin to recover from injury
• The glial cells surround neurons and provide support for
and insulation between them. Glial cells are the most
abundant cell types in the central nervous system.
• Within the pancreas there are areas that are called the
islets of Langerhans. The beta cells constitute the
predominant type of cell in the islets. The beta cells are
particularly important because they make insulin.
Degeneration of the beta cells is the main cause of type I
(insulin-dependent) diabetes mellitus.