{"id":785,"date":"2016-11-04T03:35:14","date_gmt":"2016-11-04T03:35:14","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/microbiology\/?post_type=chapter&#038;p=785"},"modified":"2018-07-12T11:16:07","modified_gmt":"2018-07-12T11:16:07","slug":"major-histocompatibility-complexes-and-antigen-presenting-cells","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/chapter\/major-histocompatibility-complexes-and-antigen-presenting-cells\/","title":{"raw":"Major Histocompatibility Complexes and Antigen-Presenting Cells","rendered":"Major Histocompatibility Complexes and Antigen-Presenting Cells"},"content":{"raw":"<div class=\"textbox learning-objectives\">\r\n<h3>Learning Objectives<\/h3>\r\n<ul>\r\n \t<li>Identify cells that express MHC I and\/or MHC II molecules and describe the structures and cellular location of MHC I and MHC II molecules<\/li>\r\n \t<li>Identify the cells that are antigen-presenting cells<\/li>\r\n \t<li>Describe the process of antigen processing and presentation with MHC I and MHC II<\/li>\r\n<\/ul>\r\n<\/div>\r\nAs discussed in <a href=\".\/chapter\/cellular-defenses\/\" target=\"_blank\" rel=\"noopener\">Cellular Defenses<\/a>, <strong>major histocompatibility complex (MHC)<\/strong> molecules are expressed on the surface of healthy cells, identifying them as normal and \"self\" to <strong>natural killer (NK) cells<\/strong>. MHC molecules also play an important role in the presentation of foreign antigens, which is a critical step in the activation of T cells and thus an important mechanism of the adaptive immune system.\r\n<h2>Major Histocompatibility Complex Molecules<\/h2>\r\nThe <strong>major histocompatibility complex<\/strong> (<strong>MHC<\/strong>) is a collection of genes coding for MHC molecules found on the surface of all nucleated cells of the body. In humans, the MHC genes are also referred to as <strong>human leukocyte antigen (HLA) genes<\/strong>. Mature <strong>red blood cells<\/strong>, which lack a nucleus, are the only cells that do not express MHC molecules on their surface.\r\n\r\nThere are two classes of MHC molecules involved in adaptive immunity, MHC I and MHC II (Figure\u00a01). <strong>MHC I<\/strong> molecules are found on all nucleated cells; they present normal <strong>self-antigens<\/strong> as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity. In contrast, <strong>MHC II<\/strong> molecules are only found on <strong>macrophages<\/strong>, <strong>dendritic cells<\/strong>, and <strong>B cells<\/strong>; they present abnormal or nonself pathogen antigens for the initial activation of T cells.\r\n\r\nBoth types of MHC molecules are transmembrane glycoproteins that assemble as dimers in the cytoplasmic membrane of cells, but their structures are quite different. MHC I molecules are composed of a longer \u03b1 protein chain coupled with a smaller <strong>\u03b2<sub>2<\/sub> microglobulin<\/strong> protein, and only the \u03b1 chain spans the cytoplasmic membrane. The \u03b1 chain of the MHC I molecule folds into three separate domains: \u03b1<sub>1<\/sub>, \u03b1<sub>2<\/sub> and \u03b1<sub>3<\/sub>. MHC II molecules are composed of two protein chains (an \u03b1 and a \u03b2 chain) that are approximately similar in length. Both chains of the MHC II molecule possess portions that span the plasma membrane, and each chain folds into two separate domains: \u03b1<sub>1<\/sub> and \u03b1<sub>2<\/sub>, and \u03b2<sub>1<\/sub>, and \u03b2<sub>2<\/sub>. In order to present abnormal or non-self-antigens to T cells, MHC molecules have a cleft that serves as the antigen-binding site near the \"top\" (or outermost) portion of the MHC-I or MHC-II dimer. For MHC I, the antigen-binding cleft is formed by the \u03b1<sub>1<\/sub> and \u03b1<sub>2<\/sub> domains, whereas for MHC II, the cleft is formed by the \u03b1<sub>1<\/sub> and \u03b2<sub>1<\/sub> domains (Figure\u00a01).\r\n\r\n[caption id=\"attachment_1695\" align=\"aligncenter\" width=\"1024\"]<img class=\"size-large wp-image-1695\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10212927\/OSC_Microbio_18_02_MHCbind1-1024x442.jpg\" alt=\" Drawing of a phospholipid bilayer (plasma membrane). An MHC Class I protein molecule is found in all nucleated body cells. It has a linear portion in the membrane and four portions on the outer side of the cell. One of these portions connects to the membrane spanning portion; two form the antigen binding site; and the fourth is labeled the Beta-2 microglobulin. MHC Class II protein molecules are found in lymphocytes and macrophages. This has two membrane spanning portions (each attached to a portion on the outside of the cell). The two portions attached to these form the antigen binding site.\" width=\"1024\" height=\"442\" \/> Figure\u00a01. MHC I are found on all nucleated body cells, and MHC II are found on macrophages, dendritic cells, and B cells (along with MHC I). The antigen-binding cleft of MHC I is formed by domains \u03b1<sub>1<\/sub> and \u03b1<sub>2<\/sub>. The antigen-binding cleft of MHC II is formed by domains \u03b1<sub>1<\/sub> and \u03b2<sub>1<\/sub>.[\/caption]\r\n<h2>Antigen-Presenting Cells (APCs)<\/h2>\r\nAll nucleated cells in the body have mechanisms for processing and presenting antigens in association with MHC molecules. This signals the immune system, indicating whether the cell is normal and healthy or infected with an intracellular pathogen. However, only macrophages, dendritic cells, and B cells have the ability to present antigens specifically for the purpose of activating T cells; for this reason, these types of cells are sometimes referred to as <strong>antigen-presenting cells (APCs)<\/strong>.\r\n\r\nWhile all APCs play a similar role in adaptive immunity, there are some important differences to consider. Macrophages and dendritic cells are <strong>phagocytes<\/strong> that ingest and kill pathogens that penetrate the first-line barriers (i.e., skin and mucous membranes). B cells, on the other hand, do not function as phagocytes but play a primary role in the production and secretion of antibodies. In addition, whereas macrophages and dendritic cells recognize pathogens through nonspecific receptor interactions (e.g., <strong>PAMPs<\/strong>, <strong>toll-like receptors<\/strong>, and receptors for opsonizing <strong>complement<\/strong> or antibody), B cells interact with foreign pathogens or their free antigens using antigen-specific immunoglobulin as receptors (monomeric <strong>IgD<\/strong> and <strong>IgM<\/strong>). When the immunoglobulin receptors bind to an antigen, the B cell internalizes the antigen by endocytosis before processing and presentting the antigen to T cells.\r\n<h3>Antigen Presentation with MHC II Molecules<\/h3>\r\n[caption id=\"\" align=\"alignright\" width=\"400\"]<img class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172644\/OSC_Microbio_18_02_APC.jpg\" alt=\"The process of phagocytosis. 1: A bacterium is engulfed by phagocytosis into a dendritic cell and is encased in a phagosome. 2: Lysosomes fuse with the phagosome and digest the bacterium. 3: Immunodominant epitopes are associated with MHC II and presented on the cell surface.\" width=\"400\" height=\"405\" \/> Figure\u00a02. A dendritic cell phagocytoses a bacterial cell and brings it into a phagosome. Lysosomes fuse with the phagosome to create a phagolysosome, where antimicrobial chemicals and enzymes degrade the bacterial cell. Proteases process bacterial antigens, and the most antigenic epitopes are selected and presented on the cell\u2019s surface in conjunction with MHC II molecules. T cells recognize the presented antigens and are thus activated.[\/caption]\r\n\r\nMHC II molecules are only found on the surface of APCs. Macrophages and dendritic cells use similar mechanisms for processing and presentation of antigens and their epitopes in association with MHC II; B cells use somewhat different mechanisms that will be described further in <a href=\".\/chapter\/b-lymphocytes-and-humoral-immunity\/\" target=\"_blank\" rel=\"noopener\">B Lymphocytes and Humoral Immunity<\/a>. For now, we will focus on the steps of the process as they pertain to dendritic cells.\r\n\r\nAfter a dendritic cell recognizes and attaches to a pathogen cell, the pathogen is internalized by phagocytosis and is initially contained within a <strong>phagosome<\/strong>. Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome, where degradation of the pathogen for antigen processing begins. Proteases (protein-degrading) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II (Figure\u00a02).\r\n\r\nAPCs do not present all possible epitopes to T cells; only a selection of the most antigenic or <strong>immunodominant<\/strong> epitopes are presented. The mechanism by which epitopes are selected for processing and presentation by an APC is complicated and not well understood; however, once the most antigenic, immunodominant epitopes have been processed, they associate within the antigen-binding cleft of MHC II molecules and are translocated to the cell surface of the dendritic cell for presentation to T cells.\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>What are the three kinds of APCs?<\/li>\r\n \t<li>What role to MHC II molecules play in antigen presentation?<\/li>\r\n \t<li>What is the role of antigen presentation in adaptive immunity?<\/li>\r\n<\/ul>\r\n<\/div>\r\n<h3>Antigen Presentation with MHC I Molecules<\/h3>\r\nMHC I molecules, found on all normal, healthy, <strong>nucleated cells<\/strong>, signal to the immune system that the cell is a normal \"self\" cell. In a healthy cell, proteins normally found in the cytoplasm are degraded by <strong>proteasomes <\/strong>(enzyme complexes responsible for degradation and processing of proteins) and processed into <strong>self-antigen epitopes<\/strong>; these self-antigen epitopes bind within the MHC I antigen-binding cleft and are then presented on the cell surface. Immune cells, such as NK cells, recognize these self-antigens and do not target the cell for destruction. However, if a cell becomes infected with an intracellular pathogen (e.g., a virus), protein antigens specific to the pathogen are processed in the proteasomes and bind with <strong>MHC I<\/strong> molecules for presentation on the cell surface. This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen.\r\n\r\nBefore elimination of infected cells can begin, APCs must first activate the T cells involved in cellular immunity. If an intracellular pathogen directly infects the cytoplasm of an APC, then the processing and presentation of antigens can occur as described (in proteasomes and on the cell surface with MHC I). However, if the intracellular pathogen does not directly infect APCs, an alternative strategy called <strong>cross-presentation<\/strong> is utilized. In cross-presentation, antigens are brought into the APC by mechanisms normally leading to presentation with MHC II (i.e., through phagocytosis), but the antigen is presented on an MHC I molecule for CD8 T cells. The exact mechanisms by which cross-presentation occur are not yet well understood, but it appears that cross-presentation is primarily a function of <strong>dendritic cells<\/strong> and not macrophages or B cells.\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>Compare and contrast antigen processing and presentation associated with MHC I and MHC II molecules.<\/li>\r\n \t<li>What is cross-presentation, and when is it likely to occur?<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Key Concepts and Summary<\/h3>\r\n<ul>\r\n \t<li><strong>Major histocompatibility complex (MHC)<\/strong> is a collection of genes coding for glycoprotein molecules expressed on the surface of all nucleated cells.<\/li>\r\n \t<li><strong>MHC I<\/strong> molecules are expressed on all nucleated cells and are essential for presentation of normal \"self\" antigens. Cells that become infected by intracellular pathogens can present foreign antigens on MHC I as well, marking the infected cell for destruction.<\/li>\r\n \t<li><strong>MHC II<\/strong> molecules are expressed only on the surface of <strong>antigen-presenting cells<\/strong> (macrophages, dendritic cells, and B cells). Antigen presentation with MHC II is essential for the activation of T cells.<\/li>\r\n \t<li><strong>Antigen-presenting cells (APCs)<\/strong> primarily ingest pathogens by phagocytosis, destroy them in the phagolysosomes, process the protein antigens, and select the most antigenic\/immunodominant epitopes with MHC II for presentation to T cells.<\/li>\r\n \t<li><strong>Cross-presentation<\/strong> is a mechanism of antigen presentation and T-cell activation used by dendritic cells not directly infected by the pathogen; it involves phagocytosis of the pathogen but presentation on MHC I rather than MHC II.<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div class=\"textbox exercises\">\r\n<h3>Multiple Choice<\/h3>\r\nMHC I molecules present ________.\r\n<ol style=\"list-style-type: lower-alpha\">\r\n \t<li>processed foreign antigens from proteasomes.<\/li>\r\n \t<li>processed self-antigens from phagolysosome.<\/li>\r\n \t<li>antibodies.<\/li>\r\n \t<li>T cell antigens.<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"293033\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"293033\"]Answer a.\u00a0MHC I molecules present processed foreign antigens from proteasomes.[\/hidden-answer]\r\n\r\nMHC II molecules present\u00a0________.\r\n<ol style=\"list-style-type: lower-alpha\">\r\n \t<li>processed self-antigens from proteasomes.<\/li>\r\n \t<li>processed foreign antigens from phagolysosomes.<\/li>\r\n \t<li>antibodies.<\/li>\r\n \t<li>T cell receptors.<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"213575\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"213575\"]Answer b.\u00a0MHC II molecules present processed foreign antigens from phagolysosomes.[\/hidden-answer]\r\n\r\nWhich type of antigen-presenting molecule is found on all nucleated cells?\r\n<ol style=\"list-style-type: lower-alpha\">\r\n \t<li>MHC I<\/li>\r\n \t<li>MHC II<\/li>\r\n \t<li>antibodies<\/li>\r\n \t<li>B-cell receptors<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"797999\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"797999\"]Answer a.\u00a0MHC I\u00a0is found on all nucleated cells.[\/hidden-answer]\r\n\r\nWhich type of antigen-presenting molecule is found only on macrophages, dendritic cells, and B cells?\r\n<ol style=\"list-style-type: lower-alpha\">\r\n \t<li>MHC I<\/li>\r\n \t<li>MHC II<\/li>\r\n \t<li>T-cell receptors<\/li>\r\n \t<li>B-cell receptors<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"136800\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"136800\"]Answer b.\u00a0MHC II\u00a0is found only on macrophages, dendritic cells, and B cells.[\/hidden-answer]\r\n\r\n<\/div>\r\n<div class=\"textbox exercises\">\r\n<h3>Fill in the Blank<\/h3>\r\nMHC molecules are used for antigen ________ to T cells.\r\n[reveal-answer q=\"122237\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"122237\"]MHC molecules are used for antigen <strong>presentation<\/strong> to T cells.[\/hidden-answer]\r\n\r\nMHC II molecules are made up of two subunits (\u03b1 and \u03b2) of approximately equal size, whereas MHC I molecules consist of a larger \u03b1 subunit and a smaller subunit called ________.\r\n[reveal-answer q=\"956676\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"956676\"]MHC II molecules are made up of two subunits (\u03b1 and \u03b2) of approximately equal size, whereas MHC I molecules consist of a larger \u03b1 subunit and a smaller subunit called <strong>\u03b2<sub>2<\/sub> microglobulin<\/strong>.[\/hidden-answer]\r\n\r\n<\/div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ol>\r\n \t<li>Which mechanism of antigen presentation would be used to present antigens from a cell infected with a virus?<\/li>\r\n \t<li>Which pathway of antigen presentation would be used to present antigens from an extracellular bacterial infection?<\/li>\r\n<\/ol>\r\n<\/div>","rendered":"<div class=\"textbox learning-objectives\">\n<h3>Learning Objectives<\/h3>\n<ul>\n<li>Identify cells that express MHC I and\/or MHC II molecules and describe the structures and cellular location of MHC I and MHC II molecules<\/li>\n<li>Identify the cells that are antigen-presenting cells<\/li>\n<li>Describe the process of antigen processing and presentation with MHC I and MHC II<\/li>\n<\/ul>\n<\/div>\n<p>As discussed in <a href=\".\/chapter\/cellular-defenses\/\" target=\"_blank\" rel=\"noopener\">Cellular Defenses<\/a>, <strong>major histocompatibility complex (MHC)<\/strong> molecules are expressed on the surface of healthy cells, identifying them as normal and &#8220;self&#8221; to <strong>natural killer (NK) cells<\/strong>. MHC molecules also play an important role in the presentation of foreign antigens, which is a critical step in the activation of T cells and thus an important mechanism of the adaptive immune system.<\/p>\n<h2>Major Histocompatibility Complex Molecules<\/h2>\n<p>The <strong>major histocompatibility complex<\/strong> (<strong>MHC<\/strong>) is a collection of genes coding for MHC molecules found on the surface of all nucleated cells of the body. In humans, the MHC genes are also referred to as <strong>human leukocyte antigen (HLA) genes<\/strong>. Mature <strong>red blood cells<\/strong>, which lack a nucleus, are the only cells that do not express MHC molecules on their surface.<\/p>\n<p>There are two classes of MHC molecules involved in adaptive immunity, MHC I and MHC II (Figure\u00a01). <strong>MHC I<\/strong> molecules are found on all nucleated cells; they present normal <strong>self-antigens<\/strong> as well as abnormal or nonself pathogens to the effector T cells involved in cellular immunity. In contrast, <strong>MHC II<\/strong> molecules are only found on <strong>macrophages<\/strong>, <strong>dendritic cells<\/strong>, and <strong>B cells<\/strong>; they present abnormal or nonself pathogen antigens for the initial activation of T cells.<\/p>\n<p>Both types of MHC molecules are transmembrane glycoproteins that assemble as dimers in the cytoplasmic membrane of cells, but their structures are quite different. MHC I molecules are composed of a longer \u03b1 protein chain coupled with a smaller <strong>\u03b2<sub>2<\/sub> microglobulin<\/strong> protein, and only the \u03b1 chain spans the cytoplasmic membrane. The \u03b1 chain of the MHC I molecule folds into three separate domains: \u03b1<sub>1<\/sub>, \u03b1<sub>2<\/sub> and \u03b1<sub>3<\/sub>. MHC II molecules are composed of two protein chains (an \u03b1 and a \u03b2 chain) that are approximately similar in length. Both chains of the MHC II molecule possess portions that span the plasma membrane, and each chain folds into two separate domains: \u03b1<sub>1<\/sub> and \u03b1<sub>2<\/sub>, and \u03b2<sub>1<\/sub>, and \u03b2<sub>2<\/sub>. In order to present abnormal or non-self-antigens to T cells, MHC molecules have a cleft that serves as the antigen-binding site near the &#8220;top&#8221; (or outermost) portion of the MHC-I or MHC-II dimer. For MHC I, the antigen-binding cleft is formed by the \u03b1<sub>1<\/sub> and \u03b1<sub>2<\/sub> domains, whereas for MHC II, the cleft is formed by the \u03b1<sub>1<\/sub> and \u03b2<sub>1<\/sub> domains (Figure\u00a01).<\/p>\n<div id=\"attachment_1695\" style=\"width: 1034px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-1695\" class=\"size-large wp-image-1695\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/10212927\/OSC_Microbio_18_02_MHCbind1-1024x442.jpg\" alt=\"Drawing of a phospholipid bilayer (plasma membrane). An MHC Class I protein molecule is found in all nucleated body cells. It has a linear portion in the membrane and four portions on the outer side of the cell. One of these portions connects to the membrane spanning portion; two form the antigen binding site; and the fourth is labeled the Beta-2 microglobulin. MHC Class II protein molecules are found in lymphocytes and macrophages. This has two membrane spanning portions (each attached to a portion on the outside of the cell). The two portions attached to these form the antigen binding site.\" width=\"1024\" height=\"442\" \/><\/p>\n<p id=\"caption-attachment-1695\" class=\"wp-caption-text\">Figure\u00a01. MHC I are found on all nucleated body cells, and MHC II are found on macrophages, dendritic cells, and B cells (along with MHC I). The antigen-binding cleft of MHC I is formed by domains \u03b1<sub>1<\/sub> and \u03b1<sub>2<\/sub>. The antigen-binding cleft of MHC II is formed by domains \u03b1<sub>1<\/sub> and \u03b2<sub>1<\/sub>.<\/p>\n<\/div>\n<h2>Antigen-Presenting Cells (APCs)<\/h2>\n<p>All nucleated cells in the body have mechanisms for processing and presenting antigens in association with MHC molecules. This signals the immune system, indicating whether the cell is normal and healthy or infected with an intracellular pathogen. However, only macrophages, dendritic cells, and B cells have the ability to present antigens specifically for the purpose of activating T cells; for this reason, these types of cells are sometimes referred to as <strong>antigen-presenting cells (APCs)<\/strong>.<\/p>\n<p>While all APCs play a similar role in adaptive immunity, there are some important differences to consider. Macrophages and dendritic cells are <strong>phagocytes<\/strong> that ingest and kill pathogens that penetrate the first-line barriers (i.e., skin and mucous membranes). B cells, on the other hand, do not function as phagocytes but play a primary role in the production and secretion of antibodies. In addition, whereas macrophages and dendritic cells recognize pathogens through nonspecific receptor interactions (e.g., <strong>PAMPs<\/strong>, <strong>toll-like receptors<\/strong>, and receptors for opsonizing <strong>complement<\/strong> or antibody), B cells interact with foreign pathogens or their free antigens using antigen-specific immunoglobulin as receptors (monomeric <strong>IgD<\/strong> and <strong>IgM<\/strong>). When the immunoglobulin receptors bind to an antigen, the B cell internalizes the antigen by endocytosis before processing and presentting the antigen to T cells.<\/p>\n<h3>Antigen Presentation with MHC II Molecules<\/h3>\n<div style=\"width: 410px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03172644\/OSC_Microbio_18_02_APC.jpg\" alt=\"The process of phagocytosis. 1: A bacterium is engulfed by phagocytosis into a dendritic cell and is encased in a phagosome. 2: Lysosomes fuse with the phagosome and digest the bacterium. 3: Immunodominant epitopes are associated with MHC II and presented on the cell surface.\" width=\"400\" height=\"405\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a02. A dendritic cell phagocytoses a bacterial cell and brings it into a phagosome. Lysosomes fuse with the phagosome to create a phagolysosome, where antimicrobial chemicals and enzymes degrade the bacterial cell. Proteases process bacterial antigens, and the most antigenic epitopes are selected and presented on the cell\u2019s surface in conjunction with MHC II molecules. T cells recognize the presented antigens and are thus activated.<\/p>\n<\/div>\n<p>MHC II molecules are only found on the surface of APCs. Macrophages and dendritic cells use similar mechanisms for processing and presentation of antigens and their epitopes in association with MHC II; B cells use somewhat different mechanisms that will be described further in <a href=\".\/chapter\/b-lymphocytes-and-humoral-immunity\/\" target=\"_blank\" rel=\"noopener\">B Lymphocytes and Humoral Immunity<\/a>. For now, we will focus on the steps of the process as they pertain to dendritic cells.<\/p>\n<p>After a dendritic cell recognizes and attaches to a pathogen cell, the pathogen is internalized by phagocytosis and is initially contained within a <strong>phagosome<\/strong>. Lysosomes containing antimicrobial enzymes and chemicals fuse with the phagosome to create a phagolysosome, where degradation of the pathogen for antigen processing begins. Proteases (protein-degrading) are especially important in antigen processing because only protein antigen epitopes are presented to T cells by MHC II (Figure\u00a02).<\/p>\n<p>APCs do not present all possible epitopes to T cells; only a selection of the most antigenic or <strong>immunodominant<\/strong> epitopes are presented. The mechanism by which epitopes are selected for processing and presentation by an APC is complicated and not well understood; however, once the most antigenic, immunodominant epitopes have been processed, they associate within the antigen-binding cleft of MHC II molecules and are translocated to the cell surface of the dendritic cell for presentation to T cells.<\/p>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>What are the three kinds of APCs?<\/li>\n<li>What role to MHC II molecules play in antigen presentation?<\/li>\n<li>What is the role of antigen presentation in adaptive immunity?<\/li>\n<\/ul>\n<\/div>\n<h3>Antigen Presentation with MHC I Molecules<\/h3>\n<p>MHC I molecules, found on all normal, healthy, <strong>nucleated cells<\/strong>, signal to the immune system that the cell is a normal &#8220;self&#8221; cell. In a healthy cell, proteins normally found in the cytoplasm are degraded by <strong>proteasomes <\/strong>(enzyme complexes responsible for degradation and processing of proteins) and processed into <strong>self-antigen epitopes<\/strong>; these self-antigen epitopes bind within the MHC I antigen-binding cleft and are then presented on the cell surface. Immune cells, such as NK cells, recognize these self-antigens and do not target the cell for destruction. However, if a cell becomes infected with an intracellular pathogen (e.g., a virus), protein antigens specific to the pathogen are processed in the proteasomes and bind with <strong>MHC I<\/strong> molecules for presentation on the cell surface. This presentation of pathogen-specific antigens with MHC I signals that the infected cell must be targeted for destruction along with the pathogen.<\/p>\n<p>Before elimination of infected cells can begin, APCs must first activate the T cells involved in cellular immunity. If an intracellular pathogen directly infects the cytoplasm of an APC, then the processing and presentation of antigens can occur as described (in proteasomes and on the cell surface with MHC I). However, if the intracellular pathogen does not directly infect APCs, an alternative strategy called <strong>cross-presentation<\/strong> is utilized. In cross-presentation, antigens are brought into the APC by mechanisms normally leading to presentation with MHC II (i.e., through phagocytosis), but the antigen is presented on an MHC I molecule for CD8 T cells. The exact mechanisms by which cross-presentation occur are not yet well understood, but it appears that cross-presentation is primarily a function of <strong>dendritic cells<\/strong> and not macrophages or B cells.<\/p>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>Compare and contrast antigen processing and presentation associated with MHC I and MHC II molecules.<\/li>\n<li>What is cross-presentation, and when is it likely to occur?<\/li>\n<\/ul>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Key Concepts and Summary<\/h3>\n<ul>\n<li><strong>Major histocompatibility complex (MHC)<\/strong> is a collection of genes coding for glycoprotein molecules expressed on the surface of all nucleated cells.<\/li>\n<li><strong>MHC I<\/strong> molecules are expressed on all nucleated cells and are essential for presentation of normal &#8220;self&#8221; antigens. Cells that become infected by intracellular pathogens can present foreign antigens on MHC I as well, marking the infected cell for destruction.<\/li>\n<li><strong>MHC II<\/strong> molecules are expressed only on the surface of <strong>antigen-presenting cells<\/strong> (macrophages, dendritic cells, and B cells). Antigen presentation with MHC II is essential for the activation of T cells.<\/li>\n<li><strong>Antigen-presenting cells (APCs)<\/strong> primarily ingest pathogens by phagocytosis, destroy them in the phagolysosomes, process the protein antigens, and select the most antigenic\/immunodominant epitopes with MHC II for presentation to T cells.<\/li>\n<li><strong>Cross-presentation<\/strong> is a mechanism of antigen presentation and T-cell activation used by dendritic cells not directly infected by the pathogen; it involves phagocytosis of the pathogen but presentation on MHC I rather than MHC II.<\/li>\n<\/ul>\n<\/div>\n<div class=\"textbox exercises\">\n<h3>Multiple Choice<\/h3>\n<p>MHC I molecules present ________.<\/p>\n<ol style=\"list-style-type: lower-alpha\">\n<li>processed foreign antigens from proteasomes.<\/li>\n<li>processed self-antigens from phagolysosome.<\/li>\n<li>antibodies.<\/li>\n<li>T cell antigens.<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q293033\">Show Answer<\/span><\/p>\n<div id=\"q293033\" class=\"hidden-answer\" style=\"display: none\">Answer a.\u00a0MHC I molecules present processed foreign antigens from proteasomes.<\/div>\n<\/div>\n<p>MHC II molecules present\u00a0________.<\/p>\n<ol style=\"list-style-type: lower-alpha\">\n<li>processed self-antigens from proteasomes.<\/li>\n<li>processed foreign antigens from phagolysosomes.<\/li>\n<li>antibodies.<\/li>\n<li>T cell receptors.<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q213575\">Show Answer<\/span><\/p>\n<div id=\"q213575\" class=\"hidden-answer\" style=\"display: none\">Answer b.\u00a0MHC II molecules present processed foreign antigens from phagolysosomes.<\/div>\n<\/div>\n<p>Which type of antigen-presenting molecule is found on all nucleated cells?<\/p>\n<ol style=\"list-style-type: lower-alpha\">\n<li>MHC I<\/li>\n<li>MHC II<\/li>\n<li>antibodies<\/li>\n<li>B-cell receptors<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q797999\">Show Answer<\/span><\/p>\n<div id=\"q797999\" class=\"hidden-answer\" style=\"display: none\">Answer a.\u00a0MHC I\u00a0is found on all nucleated cells.<\/div>\n<\/div>\n<p>Which type of antigen-presenting molecule is found only on macrophages, dendritic cells, and B cells?<\/p>\n<ol style=\"list-style-type: lower-alpha\">\n<li>MHC I<\/li>\n<li>MHC II<\/li>\n<li>T-cell receptors<\/li>\n<li>B-cell receptors<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q136800\">Show Answer<\/span><\/p>\n<div id=\"q136800\" class=\"hidden-answer\" style=\"display: none\">Answer b.\u00a0MHC II\u00a0is found only on macrophages, dendritic cells, and B cells.<\/div>\n<\/div>\n<\/div>\n<div class=\"textbox exercises\">\n<h3>Fill in the Blank<\/h3>\n<p>MHC molecules are used for antigen ________ to T cells.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q122237\">Show Answer<\/span><\/p>\n<div id=\"q122237\" class=\"hidden-answer\" style=\"display: none\">MHC molecules are used for antigen <strong>presentation<\/strong> to T cells.<\/div>\n<\/div>\n<p>MHC II molecules are made up of two subunits (\u03b1 and \u03b2) of approximately equal size, whereas MHC I molecules consist of a larger \u03b1 subunit and a smaller subunit called ________.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q956676\">Show Answer<\/span><\/p>\n<div id=\"q956676\" class=\"hidden-answer\" style=\"display: none\">MHC II molecules are made up of two subunits (\u03b1 and \u03b2) of approximately equal size, whereas MHC I molecules consist of a larger \u03b1 subunit and a smaller subunit called <strong>\u03b2<sub>2<\/sub> microglobulin<\/strong>.<\/div>\n<\/div>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ol>\n<li>Which mechanism of antigen presentation would be used to present antigens from a cell infected with a virus?<\/li>\n<li>Which pathway of antigen presentation would be used to present antigens from an extracellular bacterial infection?<\/li>\n<\/ol>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-785\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>OpenStax Microbiology. <strong>Provided by<\/strong>: OpenStax CNX. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2\">http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2<\/a>. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY: Attribution<\/a><\/em>. <strong>License Terms<\/strong>: Download for free at http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2<\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section>","protected":false},"author":17,"menu_order":3,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"OpenStax Microbiology\",\"author\":\"\",\"organization\":\"OpenStax CNX\",\"url\":\"http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"Download for free at http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-785","chapter","type-chapter","status-publish","hentry"],"part":770,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/chapters\/785","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/wp\/v2\/users\/17"}],"version-history":[{"count":4,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/chapters\/785\/revisions"}],"predecessor-version":[{"id":2209,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/chapters\/785\/revisions\/2209"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/parts\/770"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/chapters\/785\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/wp\/v2\/media?parent=785"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/pressbooks\/v2\/chapter-type?post=785"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/wp\/v2\/contributor?post=785"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-mcc-microbiology\/wp-json\/wp\/v2\/license?post=785"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}