Immunology Study Guide Lecture 9 PDF

Routes of antigen entry antigens soluble dissolve. fluids in bodily (blood lymph examples - hormones like (insulin) -antigens B lymphocytes recognize: soluble antigens (floating around in fluids in extracellular environment viral protein components) microbial surface antigens FBacterial (MHC compati...

Routes of antigen entry antigens soluble dissolve. fluids in bodily (blood lymph examples - hormones like (insulin) -antigens B lymphocytes recognize: soluble antigens (floating around in fluids in extracellular environment viral protein components) microbial surface antigens FBacterial (MHC compatibiting host cell surface antigens( cell wall Complex Major histo T lymphocytes recognize only cell-display antigens (only cell surface antigens very specific) B lymphocyte ChatGPT Route of AntigenChatGPT It seems like you're outlining the routes of antigen entry into the body and how B and entry soluble antigen T lymphocytes recognize different types of antigens. Here's a breakdown: Microbial Routes of antigen entry: Surface antigel1.Soluble antigens: These are antigens that are freely floating in body fluids, such as blood or lymph. 2.Microbial surface antigens: These are antigens present on the surface of T lymphocyte antigen of microorganisms, such as bacteria or viruses. Route blood 3.Host cell surface antigens: These are antigens present on the surface of host cells, Host cell which can be altered by infection or other factors. surface Recognition by B lymphocytes: B lymphocytes primarily recognize soluble antigens and microbial surface antigens. B Lymphoyle They do so through their surface immunoglobulin receptors (antibodies), which bind ① to these antigens. This recognition triggers B cell activation and the nids) specifically production of antibodies to neutralize the antigens. blood or lumph Recognition by T lymphocytes: ② example T lymphocytes primarily recognize antigens presented on the surface of host cells. Prented Cantigens crorganism blood to · · · Texample - - (bacteria or A ⑤ - Lymphocytes viruses) I ⑳ example Gantigenspresenteda - host cells Alter by T ens (soluble infection Lumphocytes - - or microbial surface antigen) (antibodies how ? immunoglobulin receptors this triages B celland production bind to antigen antibodies activation surface - 1 of neutraliea - This is typically in the form of peptide fragments presented by major histocompatibility complex (MHC) molecules. T cells have T cell receptors (TCRs) that specifically recognize these antigen-MHC complexes. There are two main types of T cells: cytotoxic T cells, which kill infected or abnormal cells displaying these antigens, and helper T cells, which regulate immune responses and help activate other immune cells. Pathogen entry and immune response: Once a pathogen breaches the epithelial lining (e.g., through a wound, mucosal surface, or insect bite), the innate immune system initiates its response. This includes mechanisms such as inflammation, activation of phagocytes (e.g., macrophages), and production of antimicrobial proteins. If the pathogen enters the bloodstream, it can be transported to secondary lymphoid organs such as the spleen, where immune cells such as B and T lymphocytes are located. This allows for a more focused immune response against the pathogen. It's important to note that while B cells primarily recognize soluble and microbial antigens, they can also present antigens to T cells, and vice versa. This collaboration between B and T cells is crucial for generating effective immune responses against pathogens. 1.Lymph Nodes and Antigen Collection: 1. Lymph nodes are crucial components of the lymphatic system and serve as sites where immune cells interact with antigens. They are strategically located throughout the body along lymphatic vessels. 2. Antigens from the epithelium and connective tissue can enter the lymphatic vessels and be carried to nearby lymph nodes. Within the lymph nodes, specialized antigen-presenting cells (APCs) such as dendritic cells capture these antigens. 3. Dendritic cells are particularly adept at capturing antigens in peripheral tissues and transporting them to lymph nodes, where they present these antigens to T cells, initiating immune responses. 2.Spleen and Blood-Borne Antigens: 1. The spleen is a secondary lymphoid organ located in the abdominal cavity. It plays a crucial role in filtering the blood and mounting immune responses to blood-borne pathogens. 2. Blood-borne antigens, such as those from systemic infections, are captured by various APCs present in the spleen, including dendritic cells and macrophages. 3. Similar to lymph nodes, dendritic cells in the spleen capture antigens and present them to T cells, initiating adaptive immune responses. 4. Additionally, the spleen contains specialized areas called white pulp, which are enriched with lymphocytes and are sites where immune 1 responses against blood-borne antigens are initiated. In summary, lymph nodes and the spleen serve as key sites where antigens encountered in peripheral tissues or the bloodstream are captured by APCs and presented to T cells, leading to the activation of adaptive immune responses. This coordinated process is essential for the body's defense against pathogens. lymph hodes Key Spleen De where sites blood stream antigens ener antigens captured by and APLS resented p activation to T cells Gr of adaptive immue responses 1 Role of dendritic cells (DCs) in antigen capture & presentation Regional Let's break down the role of dendritic cells (DCs) in antigen capture, activation, migration, and presentation in the context of skin and lymph nodes, focusing on T lymphocytes. 1. Antigen Capture by Dendritic Cells (DCs) in the Skin: In the skin, there are two main types of tissue-resident DCs: Langerhans cells in the epidermis and dermal DCs in the dermis. These immature DCs are specialized in capturing antigens encountered in the skin, such as pathogens or foreign substances. 2. Activation of DCs: Immature DCs are activated through recognition of Pathogen-Associated Molecular Patterns (PAMPs) or Damage-Associated Molecular Patterns (DAMPs) on pathogens or stressed cells. Additionally, cytokines released during infection or inflammation contribute to DC activation. Upon activation, DCs lose their adhesion to the epithelia. 3. Migration of DCs via Lymphatics: Activated DCs express the chemokine receptor CCR7, which responds to chemokines produced in lymph nodes. This expression of CCR7 facilitates the migration of activated DCs from the peripheral 2 tissues (skin) to the draining lymph nodes via the lymphatic vessels. 4. Lymph Node: Activated DCs Presenting Antigen to Naïve T Cells: In the lymph nodes, activated DCs enter the T cell zone. The T cell zone is a region in the lymph node where interactions between DCs and T cells take place. 5. Immature vs. Mature DCs: Immature DCs, found in the periphery, primarily focus on antigen capture. Activation leads to the maturation of DCs, marked by gene expression changes. Mature DCs have decreased expression of PAMP receptors and increased expression of T cell-activating molecules (costimulators) and presenting proteins. 6. T Cell Activation: Mature DCs present captured antigens to naïve T cells, initiating T cell activation. This interaction is facilitated by the binding of the T cell receptor (TCR) on the T cell to the antigen-Major Histocompatibility Complex (MHC) complex presented by the DC. Costimulatory signals from the mature DCs are crucial for full T cell activation. In summary, DCs play a crucial role in linking the innate and adaptive immune responses by capturing, processing, and presenting antigens to T cells, which is essential for the initiation of specific immune responses. 2 Antigen-presenting cells (APCs) activate CD4+ T lymphocytes 1. Antigen-Presenting Cells (APCs) Activate CD4+ Lymphocytes: Antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells, play a crucial role in activating CD4+ T lymphocytes. APCs capture antigens and present them to CD4+ T cells in the context of Major Histocompatibility Complex class II (MHC-II) molecules. 2. Dendritic Cells: Dendritic cells are specialized APCs involved in antigen uptake, processing, and presentation to CD4+ T cells. Costimulatory molecules, such as B7 on dendritic cells, interact with CD28 on naïve T cells, providing the second signal necessary for T cell activation. 3. Macrophages: Macrophages are another type of APC capable of antigen uptake and presentation to CD4+ T cells. Upon interaction with activated CD4+ T cells, macrophages receive signals that enhance their microbicidal activity. This interaction is essential for cell-mediated immunity, where activated macrophages play a crucial role in killing ingested microbes. 4. B Cells: B cells also act as APCs, presenting antigens to CD4+ T cells. 3 Interaction between activated CD4+ T cells and B cells leads to B cell activation and differentiation into antibody-secreting plasma cells. This process is critical for humoral immunity, where antibodies produced by B cells target pathogens in the bloodstream. Activation of CD4+ T Cells: Upon activation by APCs presenting antigens, CD4+ T cells undergo clonal expansion and differentiation into effector T cells. Effector T cells carry out specific functions depending on the type of immune response required, such as helping macrophages kill ingested microbes or activating B cells to produce antibodies. Positive Feedback Loop: Activation of CD4+ T cells is enhanced by cytokines and cell surface molecules. This forms a positive feedback loop where cytokines released by activated T cells further stimulate APCs and other immune cells, amplifying the immune response. Summary: APCs, including dendritic cells, macrophages, and B cells, play crucial roles in activating CD4+ T cells by presenting antigens. Activated CD4+ T cells interact with APCs to enhance their functions, leading to effective immune responses, including cell-mediated and humoral immunity. Positive feedback loops involving cytokines and cell surface molecules further amplify the immune response, ensuring an appropriate and robust defense against pathogens. 3 MHC cell surface proteins present peptide antigens to T cell receptors (TCRs) MHC = Major Histocompatibility Complex Certainly! Let's break down the components involved in the interaction between a T cell receptor (TCR) and the peptide-Major Histocompatibility Complex (MHC) complex: 1. T Cell Receptor (TCR): The TCR is a specialized protein receptor expressed on the surface of T cells. It consists of two protein chains: α and β (in the case of αβ T cells), or γ and δ (in the case of γδ T cells). The TCR is responsible for recognizing antigens presented by MHC molecules on the surface of antigen-presenting cells (APCs) or other target cells. 2. T Cell Contact Residue of Peptide: This refers to the specific amino acid residue within the peptide antigen that directly interacts with the TCR. The TCR recognizes a short peptide fragment (usually 8-10 amino acids in length) presented by the MHC molecule. 3. Peptide: Peptides are short chains of amino acids, typically derived from proteins degraded within the cell. They are presented by MHC molecules on the cell surface for recognition by T cells. The sequence and composition of the peptide determine its binding affinity to the 5 polymorphic polymorphicmeans that MHC MOLECULES vary between indivuals in their amnio acid squence -many amnio acid residues within the MHC molecule are polymorphic and determine specificy of peptide binding -these polymorphic residues interact with specific amnio acids in the peptide, contributing to the binding specificty of peptide MGC molecule MHC molecule and its recognition by the TCR. 4. Polymorphic Residue of MHC: MHC molecules are highly polymorphic, meaning they vary between individuals in their amino acid sequences. Certain amino acid residues within the MHC molecule are polymorphic and play a critical role in determining the specificity of peptide binding. 5. anchor residues are spefic amnio These polymorphic residues interact with specific amino acids in the peptide, acids within a peptide contributing to the binding specificity of the peptide-MHC complex. ssquence that interact with pockets or 5. Anchor Residue of Peptide: binding site wintin the Anchor residues are specific amino acids within the peptide sequence that interact molecule with pockets or binding sites within the MHC molecule. These anchor residues contribute to the stability and specificity of peptide-MHC binding. Anchor residues are often located at positions within the peptide that are critical for peptide-MHC complex formation. 6. Pocket of MHC- this is 6. "Pocket" of MHC: where the MHC molecules contain binding pockets or grooves where the peptide antigen binds. peptide antigen binds These pockets accommodate specific amino acid residues of the peptide, contributing to the specificity of peptide-MHC binding. The shape and chemical properties of these pockets influence the peptide-binding specificity of the MHC molecule. 7. MHC (Major Histocompatibility Complex): MHC molecules are cell surface proteins that play a central role in antigen presentation to T cells. They are divided into two main classes: MHC class I and MHC class II. MHC class I molecules present peptides derived from intracellular proteins to CD8+ T cells, while MHC class II molecules present peptides from extracellular proteins to CD4+ T cells. In summary, the interaction between a TCR and the peptide-MHC complex involves specific recognition of both the peptide and the MHC molecule. The TCR recognizes a specific peptide presented by the MHC molecule, with both the peptide sequence and the polymorphic residues of the MHC contributing to the specificity of the interaction. This recognition is essential for initiating T cell responses against foreign antigens. 7. MHC- are cell surface proteins that are important in antigen presentation to t cells they hav2 two classes - MHC CLASS 1 AND MHC CLASS II - MHC class i- present peptides derveied from intracellular proteins to c84 t cells - MHC class II molecules present peptides from extracellular proteins to cd4 t cell mch class 1- intracellular prtoeins to cd8 t cells mch class II- extracelluar proteins to cd4 t cells 5 MHC gene loci were identified in work on tissue transplantation Human Leukocyte Antigen On Chromosome 6 On Chromosome 17 indeed, the Major Histocompatibility Complex (MHC) gene loci play a crucial role in tissue transplantation and immune responses. Let's explore the significance of MHCs and the distinction between Class I and Class II MHC loci: 1. MHC Gene Loci and Tissue Transplantation: The MHC gene loci, also known as the Human Leukocyte Antigen (HLA) complex in humans, were initially identified through research on tissue transplantation. These loci contain genes that encode for MHC proteins, which are cell surface molecules involved in antigen presentation to T cells. The diversity of MHC genes within the population contributes to the success or failure of tissue and organ transplantation. Matching MHC alleles between the donor and recipient increases the likelihood of transplant success by reducing the risk of rejection. 2. MHCs as Key Antigens in Tissue Transplantation: MHC molecules are critical antigens in tissue transplantation because they are highly polymorphic, meaning they vary between individuals. When tissues or organs from a donor with different MHC alleles are transplanted into a recipient, the recipient's immune system may recognize the donor's MHC molecules as foreign and mount an immune response, leading to rejection of the transplant. MHC molecules are polymorphic this means they vary between indivuals if the tissues of donor with different MHC alllesles are tranplanted the immune system will responsed because it is different and will recongize it has forgein and this will leas to rejection - matchibg MCH ALLES between donor and recepitent minimize risk of immune rejection 6 Matching MHC alleles between the donor and recipient helps minimize the risk of immune rejection and improves transplant outcomes. 3. MHCs in Immune Responses to Protein Antigens: MHC molecules are essential for the immune system's recognition and response to protein antigens, including both foreign and self-antigens. Class I MHC molecules primarily present peptides derived from intracellular proteins to CD8+ T cells, which are involved in cell-mediated immune responses against infected or abnormal cells. Class II MHC molecules present peptides derived from extracellular proteins to CD4+ T cells, which help regulate immune responses and facilitate interactions between different immune cells. 4. Class I and Class II MHC Loci: The MHC complex contains multiple gene loci, including Class I and Class II loci. Class I MHC loci encode for MHC class I molecules, which are expressed on the surface of all nucleated cells and present peptides derived from intracellular proteins. Class II MHC loci encode for MHC class II molecules, which are primarily expressed on the surface of antigen-presenting cells (such as dendritic cells, macrophages, and B cells) and present peptides derived from extracellular proteins. In summary, the MHC gene loci encode for MHC proteins, which are critical for tissue transplantation success and immune responses to protein antigens. Matching MHC alleles between donor and recipient is essential for reducing the risk of rejection in transplantation. Class I and Class II MHC molecules play distinct roles in presenting peptides derived from different sources, contributing to the specificity and effectiveness of immune responses. MHC GENE LOCI ENCODE FOR mhc protein and is important for tissue transplation success and immune responses to protein antigens 6 There are two main classes of MHC cell surface proteins Certainly! Let's break down the concepts of MHC classes, polymorphic and nonpolymorphic genes, MHC haplotypes, and their co-dominant inheritance: 1. MHC Classes: MHC molecules are divided into two main classes: Class I and Class II. Class I MHC molecules are recognized by CD8+ cytotoxic T lymphocytes (CTLs) and primarily present peptides derived from intracellular proteins. Class II MHC molecules are recognized by CD4+ helper T cells and primarily present peptides derived from extracellular proteins. 2. Polymorphic and Nonpolymorphic Genes: MHC genes are highly polymorphic, meaning they exist in multiple forms or alleles within the population. The polymorphic genes encode for the antigen-binding regions of MHC molecules, which are critical for presenting a diverse range of peptides to T cells. In addition to polymorphic genes, there are several nonpolymorphic genes encoded at the MHC locus. These genes may play roles in immune regulation, antigen processing, or other functions. polymorphic genes encode FOR the antigen binding of MHC MOLECULES WHICH are critical for presenting a diverse range of peptides 3. MHC Haplotypes: An MHC haplotype refers to the complete set of MHC alleles present on a single chromosome. MHC hallotype- complete set of MHC alleles present on a single chromsome - each indicvual inherits one haplotype from each parent 7 Each individual inherits one haplotype from each parent, resulting in two sets of MHC alleles. MHC haplotypes are highly diverse within the population, contributing to the variability in immune responses and disease susceptibility. 4. Co-Dominant Inheritance: MHC haplotypes exhibit co-dominant inheritance, meaning that both sets of alleles are expressed and contribute to the individual's MHC phenotype. In contrast to dominant-recessive inheritance, where one allele is dominant over the other and masks its expression, co-dominant inheritance results in the expression of both alleles. This co-dominant expression allows for the presentation of a diverse range of peptides by MHC molecules, maximizing the immune system's ability to recognize and respond to pathogens. Significance: The polymorphic nature of MHC genes and the co-dominant inheritance of MHC haplotypes contribute to the diversity and specificity of immune responses. Individuals with different MHC haplotypes may have varying abilities to recognize and respond to pathogens, influencing susceptibility to infectious diseases and autoimmune disorders. Understanding MHC diversity and inheritance patterns is crucial for transplantation matching, vaccine development, and understanding immune-mediated diseases. In summary, MHC molecules play a central role in antigen presentation and immune responses, with Class I and Class II MHC molecules recognized by different subsets of T cells. The polymorphic and nonpolymorphic genes within the MHC locus, along with co-dominant inheritance of MHC haplotypes, contribute to the diversity and specificity of immune responses within the population. 7 Class II HLA gene loci code for a and b chains A heterodimer is a protein complex composed of two different protein subunits or chains. In the context of Class II HLA gene loci, the heterodimer refers to the structure formed when one alpha chain and one beta chain combine. Here's a breakdown of the components: 1.Alpha Chain: The alpha chain is encoded by genes within the Class II HLA gene loci. Each alpha chain is represented by multiple alleles within the human population. These alleles encode for slightly different versions of the alpha chain protein, resulting in variability in the structure and function of the alpha chain. 2.Beta Chain: Similarly, the beta chain is also encoded by genes within the Class II HLA gene loci and is represented by multiple alleles. Like the alpha chain alleles, the beta chain alleles encode for different versions of the beta chain protein, contributing to variability. 3.Heterodimer Formation: When an alpha chain and a beta chain come together, they form a heterodimeric protein complex. This heterodimeric structure is essential for the proper functioning of Class II MHC molecules in antigen presentation. In summary, a heterodimer in the context of Class II HLA gene loci refers to the protein complex formed by the combination of one alpha chain and one beta chain. The variability in the alleles encoding these chains contributes to the diversity of Class II MHC molecules, allowing for the presentation of a wide range of peptide antigens 8 to CD4+ helper T cells. Heterodimer is a protein complex xomposed of two different protein subunits or chains in class II HLA gene loci- it refers to the struture formed when one alpha and beta chain combine both the beta and alpha chain encoded genes within the class II HLA gene loci and they represented by muliple allels. - both encoded for their different version. of chain protein and this leads to variability 8 MHC molecular structure Class I Class II Certainly! Let's delve into the molecular structure of Class I and Class II MHC molecules, focusing on the peptide binding cleft and the process of antigen presentation: 1. Class II MHC Molecular Structure: Class II MHC molecules are heterodimeric proteins composed of two different chains: an alpha chain and a beta chain. Each chain consists of extracellular domains, a transmembrane region, and cytoplasmic tails. The extracellular domains of both chains form the peptide binding cleft, which is the region where peptide antigens are bound and presented to CD4+ helper T cells. Class II MHC molecules are primarily expressed on the surface of professional antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. 2. Class I MHC Molecular Structure: Class I MHC molecules are also heterodimeric proteins composed of an alpha chain and a beta-2 microglobulin (β2m) chain. Like Class II MHC molecules, Class I MHC molecules have extracellular domains that form the peptide binding cleft. However, Class I MHC molecules are expressed on the surface of almost all nucleated cells in the body, allowing them to present intracellular peptides to CD8+ class II MHC Molecular structure- they are heterodimeric proteins composed of alpha and beta chains - chain consists of extracellular domains, trnasmembrane region and cytoplasmic tails - extracellular domians of both chains form a binding cleft which is the region where the peptide antigen are presented to cd4+ helper cells Class I MHC MOLECULEAR struture- they are also heterdimeric proteins they have extracellualr domians to that form a peptide bidnning cleft. but they are expressed on the surface of almost all nucleated cekks in the body allowing them to present intracellualr peptides to cd8 cytotoxic t cells 9 cytotoxic T cells. Peptide Binding Cleft: The peptide binding cleft is a groove or pocket formed by the α1 and β1 domains of Class II MHC molecules or the α1 and α2 domains of Class I MHC molecules. This cleft is highly polymorphic, allowing it to accommodate a wide variety of peptide sequences. Peptide binding to the cleft occurs via interactions between amino acid residues of the peptide and specific pockets or residues within the cleft. The peptide binding cleft of Class II MHC molecules is open at both ends, allowing longer peptides (typically 13-25 amino acids) to bind. In contrast, the peptide binding cleft of Class I MHC molecules is closed at one end, limiting the length of peptides that can bind (usually 8-10 amino acids). Antigen Presentation: The process of antigen presentation involves the binding of peptide antigens to the peptide binding cleft of MHC molecules. Peptides are typically derived from proteins degraded within the cell and are transported into the endoplasmic reticulum (ER), where they associate with Class I MHC molecules. Peptides derived from extracellular proteins are taken up by professional APCs, processed, and loaded onto Class II MHC molecules within specialized endosomal compartments. Once bound to MHC molecules, peptide antigens are presented on the cell surface for recognition by T cell receptors (TCRs) on CD4+ helper T cells (Class II MHC) or CD8+ cytotoxic T cells (Class I MHC). This interaction between MHC-bound peptide antigens and TCRs initiates immune responses, leading to T cell activation and the coordination of adaptive immune responses. In summary, the peptide binding cleft of MHC molecules plays a critical role in antigen presentation to T cells, allowing the immune system to detect and respond to a wide range of pathogens and abnormal cells. The structural differences between Class I and Class II MHC molecules influence the types of peptides they can bind and present, as well as their cellular distribution and functions in the immune response. 9 The peptide-binding cleft contains many polymorphic AAs Variability Greatest Intermediate Least ChatGPT ChatGPT Absolutely, the polymorphic amino acids within the peptide-binding cleft of MHC molecules contribute significantly to the variability and diversity of the immune response. Here's a breakdown of how this variability influences antigen presentation and T cell recognition in Class I and Class II MHC molecules: 1. Polymorphic Amino Acids in the Peptide-Binding Cleft: The peptide-binding cleft of both Class I and Class II MHC molecules contains numerous polymorphic amino acids. These polymorphic amino acids create structural diversity within the cleft, allowing MHC molecules to accommodate a wide range of peptide sequences. The variability in amino acid residues within the cleft influences the binding specificity and affinity of MHC molecules for different peptides. 2. Variability in MHC Molecules: Class I MHC molecules exhibit the greatest variability in their peptide-binding clefts. This high variability allows Class I MHC molecules to bind and present a diverse array of peptides derived from intracellular proteins. Class II MHC molecules have an intermediate level of variability in their peptide- 10 binding clefts. They primarily present peptides derived from extracellular proteins and have evolved to accommodate a broader range of peptide sequences compared to Class I MHC molecules. Despite having the least variability in their peptide-binding clefts, Class II MHC molecules still exhibit sufficient diversity to present a wide variety of peptides to T cells. 3. Recognition of Different Antigens by T Cells: Each MHC molecule can only bind a single peptide at a time within its peptidebinding cleft. However, a given MHC molecule is capable of binding many different peptides over time, due to its structural flexibility and the variability of amino acid residues within the cleft. This ability to bind multiple peptides enables MHC molecules to present a diverse repertoire of antigens to T cells, allowing for the recognition of a wide range of pathogens and abnormal cells by the immune system. T cells, equipped with diverse T cell receptors (TCRs), are capable of recognizing and responding to these antigen-MHC complexes, initiating appropriate immune responses against the specific antigens presented. In summary, the polymorphic amino acids within the peptide-binding cleft of MHC molecules contribute to the variability and diversity of antigen presentation. This variability allows MHC molecules to bind and present a wide range of peptides to T cells, facilitating the recognition and response to diverse pathogens and antigens by the immune system. 10