Podcast
Questions and Answers
What is the role of the non-polymorphic areas in MHC molecules?
What is the role of the non-polymorphic areas in MHC molecules?
Which characteristic of peptide binding to MHC is most accurate?
Which characteristic of peptide binding to MHC is most accurate?
What feature distinguishes T cell recognition from that of B cells?
What feature distinguishes T cell recognition from that of B cells?
Which statement best explains MHC class II polymorphism?
Which statement best explains MHC class II polymorphism?
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What is the significance of self-association in MHC class II molecules?
What is the significance of self-association in MHC class II molecules?
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Which characteristic defines an immunogen?
Which characteristic defines an immunogen?
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What distinguishes antigens from immunogens?
What distinguishes antigens from immunogens?
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Which statement about antibodies is true?
Which statement about antibodies is true?
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Which of the following substances is classified as an antigen?
Which of the following substances is classified as an antigen?
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What is the primary function of antigens?
What is the primary function of antigens?
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Which of the following statements correctly describes an example of antigens?
Which of the following statements correctly describes an example of antigens?
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Which scenario best illustrates the concept of an immunogen?
Which scenario best illustrates the concept of an immunogen?
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What determines the likelihood that a graft will be accepted by a recipient's immune system?
What determines the likelihood that a graft will be accepted by a recipient's immune system?
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Which HLA proteins are encoded by the Class II locus?
Which HLA proteins are encoded by the Class II locus?
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How many sets of MHC haplotypes does each individual inherit?
How many sets of MHC haplotypes does each individual inherit?
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What is the total number of HLA alleles with different amino acid sequences known?
What is the total number of HLA alleles with different amino acid sequences known?
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What is the chance that two siblings will inherit identical sets of HLA alleles?
What is the chance that two siblings will inherit identical sets of HLA alleles?
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What is the primary physiological function of MHC molecules?
What is the primary physiological function of MHC molecules?
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What defines a MHC haplotype?
What defines a MHC haplotype?
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What mechanism is responsible for the expression of HLA alleles?
What mechanism is responsible for the expression of HLA alleles?
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What does polymorphism in MHC molecules contribute to?
What does polymorphism in MHC molecules contribute to?
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What is one consequence of the high polymorphism observed in HLA genes?
What is one consequence of the high polymorphism observed in HLA genes?
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What does TI-1 antigen require to induce an immune response?
What does TI-1 antigen require to induce an immune response?
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What is the main characteristic of a tolerogen?
What is the main characteristic of a tolerogen?
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Which of the following statements about TI-2 antigens is accurate?
Which of the following statements about TI-2 antigens is accurate?
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What is the role of antigen presenting cells (APCs) in antigen processing?
What is the role of antigen presenting cells (APCs) in antigen processing?
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Which type of antigen typically arises from tumor-specific mutations?
Which type of antigen typically arises from tumor-specific mutations?
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Which of the following statements about haptens is true?
Which of the following statements about haptens is true?
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Exogenous antigens are primarily taken up by what mechanism?
Exogenous antigens are primarily taken up by what mechanism?
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What distinguishes MHC Class I molecules from Class II molecules?
What distinguishes MHC Class I molecules from Class II molecules?
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What differentiates tumor-associated antigens (TAAs) from tumor-specific antigens (TSAs)?
What differentiates tumor-associated antigens (TAAs) from tumor-specific antigens (TSAs)?
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What role do epitopes play in immunology?
What role do epitopes play in immunology?
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How does the polymorphism of MHC genes impact the immune response?
How does the polymorphism of MHC genes impact the immune response?
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What type of response is generally associated with TI-1 antigens?
What type of response is generally associated with TI-1 antigens?
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Which characteristic is generally associated with proteins as immunogens?
Which characteristic is generally associated with proteins as immunogens?
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What is a defining feature of TC epitopes?
What is a defining feature of TC epitopes?
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Which of the following correctly describes how TLRs contribute to TI-1 antigen responses?
Which of the following correctly describes how TLRs contribute to TI-1 antigen responses?
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Which type of antigen is more likely to provoke a non-specific immune response?
Which type of antigen is more likely to provoke a non-specific immune response?
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In what way do polysaccharides and glycoproteins interact with B cell receptors (BCR)?
In what way do polysaccharides and glycoproteins interact with B cell receptors (BCR)?
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What happens to a tolerogen if its molecular form is changed?
What happens to a tolerogen if its molecular form is changed?
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Study Notes
Antigens, Antigen Processing & Presentation
- Introduction to the topic of antigens, antigen processing, and presentation within the context of medical microbiology. The presentation outlines lecture objectives and key information on antigens and their role in triggering the immune response.
- Lecture Objectives: Students will be able to differentiate between antigens, immunogens, epitopes, and haptens; recognize the different types of antigens and their immunogenicity; define T-dependent and T-independent antigens; describe the inheritance pattern of MHC; contrast the cellular expression of MHC Class I vs MHC Class II molecules; identify the most polymorphic MHC Class I and Class II genes and their importance for antigen processing and transplantation; diagram and label a Class I and Class II MHC molecule as it appears on the surface of a cell; identify the key steps in exogenous and endogenous antigen processing, including the role of TAP, proteasomes, chaperones, invariant chain/CLIP, and HLA-DM; and describe the cellular/molecular mechanism and significance of cross-presentation in activation of CD8+ T cells.
What is it that Our Immune System Recognizes?
- Key differences in antigens, immunogens, epitopes, and haptens.
- Classifying antigens based on their immunogenicity.
Antigens
- Descriptions and examples of various types of antigens, including neoplastic or normal host cells (e.g., cancerous or normal prostate cells), microbial proteins/carbohydrates (e.g., Streptococcus pneumoniae), viral proteins, and environmental factors (e.g., pollen and animal dander).
- Illustration of specific examples of antigens.
Terms to Know: Antigens & Immunogens
- Definition of antigen (Ag): substance that reacts with products of a specific immune response; a molecule recognized by receptors on T or B cells.
- Definition of immunogen: a substance that induces a specific immune response (binding to TCR or BCR/antibody).
- Definition of antibody (Ab): a specific protein produced in response to an immunogen, which reacts with an antigen.
- Importance of distinguishing between immunogens and antigens.
An Antigen by Any Other Name...
- Definition and characteristics of an allergen, a substance causing a detrimental allergic reaction.
- Definition and characteristics of a tolerogen, an antigen that invokes a specific immune non-responsiveness due to its molecular form.
- Definition and characteristics of tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs).
Terms to Know: Epitope
- Definition of epitope (aka antigenic determinant): the portion of an antigen that combines with the products of a specific immune response.
- Distinction between B cell and T cell epitopes, emphasizing differences in the types of molecules (e.g., linear or conformational) that comprise the epitopes.
Chemical Nature of Different Types of Antigens
- Types of antigens: proteins (e.g., pure proteins, glycoproteins, lipoproteins); polysaccharides (e.g., pure polysaccharides, lipopolysaccharides); nucleic acids (poorly immunogenic potentially when single-stranded or complexed with proteins); and lipids (non-immunogenic or potential haptens).
- Explanation of haptens: low molecular weight, small compounds requiring linkage with other larger molecules (like proteins) for the body to recognize them as an immunogen.
Relative Immunogenicity of Various Antigens
- Hierarchy of antigenicity for different molecules (e.g., proteins, carbohydrates, etc.).
- Explanation of how haptens need larger molecules for the immune system to respond.
Features of Biological Antigens Recognized
- B cell epitopes, encompassing macromolecules; proteins, polysaccharides, nucleic acids, lipids, and small chemicals, are recognized by BCR (B-cell receptor) or soluble antibody; with both extracellular or cell-surface presentation
- T cell epitopes, often peptide segments, are recognized when bound to MHC molecules.
Antigens Stimulate Adaptive Immune Responses
- Overview of how antigens trigger humoral and cellular immunity via the activation of B-cells, T-cells (helper and cytotoxic) and various other mechanisms such as phagocytosis
How Do The Immune System Stimulate Adaptive Responses
- How innate immune responses assist the adaptive immune system to launch an effective response.
- Signals (signal 1, 2) required for lymphocyte activation, including antigen recognition, and the role of cytokines, microbial peptides, and microbial degradation products during innate immune responses.
Recognition by Lymphocytes
- Cell-mediated immunity using T cells, including T-helper cells (CD4+) and cytotoxic T cells (CD8+).
- The role of receptors on lymphocytes (membrane-bound BCR/TCR), as well as soluble antibodies.
- The function of accessory molecules, specifically the Major Histocompatibility Complex (MHC) types I and II, as crucial players in activating T helper and cytotoxic T cells, and providing antigen presentation to B-cells.
- Clarification, using several pathways, on class I and class II MHC antigen recognition, including cells and molecules involved in presentation.
Antigens Can Elicit a B Cell Response in Two Primary Ways
- Difference between T-dependent antigens (T-D) and T-independent antigens (T-I).
- Exogenous Antigens: Cellular components, intracellular pathogens, e.g., autoantigens and alloantigens, with specific examples. Intracellular Pathogens: viruses, intracellular bacteria and parasites.
- The importance of MHC-associated antigen presentation in T cell activation and B-cell interactions is highlighted.
Antigens Can Elicit a B Cell Response in Two Primary Ways- continued
- Characteristics of T-independent antigens (TI-1): activation independent of T cell help
- Characteristics of T-independent antigens (TI-2): activation influenced by T cell cytokines
- Polymeric antigens are a specific type of TI-2 antigen, often polysaccharides and glycoproteins.
Thymus-Dependent vs. Thymus-Independent Antigens
- Key features of thymus-dependent antigens (protein antigens) in terms of isotype switching, affinity maturation, and secondary response (memory B cells).
- Thymus-independent antigens (polymeric antigens like polysaccharides) often exhibit characteristics of less robust antibody response, especially regarding isotype switching, affinity maturation, and secondary response.
Antigen Processing and Presentation to T Cells
- Overview of antigen-processing mechanisms as the presentation of processed peptides on MHC molecules for recognition by T cells.
- The ability of an antigen presenting cell (APC) to convert naturally occurring proteins into peptides suitable for binding to MHC molecules.
How Are MHC Molecules Inherited?
- MHC molecules are inherited via a specific inheritance pattern.
- The high polymorphism in MHC genes; a critical factor in antigen processing, especially in transplant rejection.
Discovery of the Human Major Histocompatibility Complex (MHC)
- History and significance of the discovery of MHC.
- Role of these molecules in tissue transplantation, and in the immune system generally.
- Crucial role of HLA proteins in tissue transplantation and rejection, due to their variability in individuals.
Proteins Encoded by MHC (HLA)
- Breakdown of MHC Class I and Class II genes, highlighting specific examples of proteins like HLA-A, B, C, DQ, DR as well as other loci. The presentation emphasizes the link between specific chromosomes and the expression of these crucial proteins for immunity.
- Overview on how MHC haplotypes are inherited, with the importance highlighted on understanding the genetics of immune response. Emphasis placed on the role of siblings inheriting identical MHC haplotypes as a critical characteristic in immune recognition and transplantation.
Inheritance and Expression of MHC
- Each haplotype contains genes for MHC Class I and II molecules. Inheritance from parents is explored.
- Co-dominant expression of the MHC is a critical feature from both parental haplotypes
Implications of Polymorphism
- Polymorphic genes: crucial for recognizing a wide range of microbial peptides.
- Importance of polymorphism for effective immunity is highlighted. In transplantation, understanding the polymorphic nature of MHC is critical in determining compatibility, thus reducing the chance of rejection.
Implications of Polymorphism (continued)
- Histocompatibility molecules: how an MHC molecule, which differs between individuals, determines the susceptibility to transplant rejection.
- Allogeneic reactions: how different MHC molecules are recognized by the recipient's immune system, leading to an immune response against the donor tissue.
- HLA: critical in cases of transplantation to determine donor and recipient compatibility.
What Does the MHC Molecule Look Like?
- Contrast between Class I and Class II MHC molecules, emphasizing polypeptide chains, beta 2 microglobulin, peptide-binding grooves, anchor residues/pockets, and TCR/CD4/CD8 binding sites. A clear diagram would show the structural differences between these two.
Which Cells Express which MHC?
- Categorization of cells that express Class I and Class II MHC molecules.
- Overview of the cell types that express these molecules.
- Highlighting which cell types are the antigen presenting cells (APCs).
MHC Structure
- Detailed breakdown of the structure of MHC class I, including the subunits, peptide-binding cleft, and the role of specific residues inside of the cleft.
- Clear presentation of MHC class II structure, including subunits, peptide-binding site, and association with various molecules; such as CD4. This provides a detailed understanding of the spatial arrangement of each subunit.
Peptide Binding
- MHC polymorphism is predominantly based in the peptide-binding region.
- Differences between MHC isoforms to highlight peptide binding diversity.
- Importance of isoform binding in regulating immune responses.
Features of Peptide Binding to MHC
- Broad specificity of how peptides bind to MHC molecules, enabling numerous peptide-MHC interactions based on structure; which recognizes a wide array of peptides.
- Each MHC molecule displays a single peptide at a time and recognizes only peptides.
Features of Peptide Binding to MHC (continued)
- MHC-restricted T cells, which can recognize a vast range of protein antigens.
- Different MHC molecules with broad specificity for recognition of an array of peptides.
- How peptides presented by MHC molecules dictate if T cells respond or not (and how).
Antigen Processing and Presentation Pathways
- Overview of the steps in antigen processing and presentation, highlighting differences between processing exogenous and endogenous antigens. This section should contain clear diagrams.
- Detailed discussion of the processes involved in either exogenous or endogenous antigen processing. This includes the various steps and molecules, like TAP, proteasomes, chaperones, invariant chain/CLIP, and HLA-DM
Antigen Processing and Presentation Pathways
- Details of the pathways used in processing exogenous antigens versus endogenous antigens.
Features of the Antigen Processing Pathways
- Summary of the features and key molecules involved in the MHC class I and class II pathways, including the roles of TAP, DM/CLIP complex, and other relevant proteins.
- Clear presentation of similarities and differences between processing exogenous vs endogenous antigens.
Just When You Had It Down, Here's a New Way of Activating CD8+ T Cells
- The mechanistic details of cross-presentation pathway.
- The significance of cross-presentation in CD8+ T cell activation will also be highlighted.
Cross Presentation (AKA Cross-Priming)
- Antigen capture and processing
- Cross-presentation pathway overview—specifically how professional antigen-presenting cells (APCs typically dendritic cells), can internalize and process exogenous proteins and present them on MHC I molecules to activate CD8+ T cells.
- Explanation of the process of cross-presentation in dendritic cells.
Cross Presentation: What Happens When an Infected Cell is Ingested-1
- The ingestion of cells infected with intracellular pathogens and the attempts of these infected cells to process the viral antigen via the class I MHC pathway.
- The significance of why these cells lack a proper immune response.
- The process of how infected cells can no longer infect other cells is detailed.
Cross Presentation: What Happens When an Infected Cell is Ingested-2
- How the infected cell is taken up by professional APCs and presented to CD8 T cells via Cross Presentation.
- Overview of how these cells are taken up by professional APCs, and how viral proteins are presented to these CD8+ T cells. Distress signals on infected cells are discussed.
Cross Presentation: What Happens When an Infected Cell is Ingested-3
- Details of the ingested infected cell antigen processing and presentation via MHC I to activate CD8+ T cells (CTLs).
- Outline of the alternate pathway of processing and presentation of endogenous antigens by MHC II molecules. This gives an understanding on how these cells can recognize microbe-derived antigens from the ingested cell via class I MHC molecules and stimulate CD8+ CTLs.
A Model for T Cell Recognition of a Peptide-MHC Complex
- How immune cells recognize peptides that are presented on MHC molecules.
What Are the Steps in the MHC Pathways of Peptide Degradation and Presentation?
- Overview of the different steps in how exogenous and endogenous peptides are processed.
- Steps taken with the proteins internalized by the APC, starting from the uptake, processing, to presenting of antigens on MHC molecules for T-helper (CD4+) and cytotoxic (CD8+) T cell recognition.
Overview of Antigen Processing and Presentation
- Overview of antigen processing and presentation pathways, with consideration of how microbes enter the immune system.
Overview of Antigen Processing and Presentation Pathways (continued)
- Detailed description of two pathways: exogenous antigen pathway, and endogenous antigen pathway, highlighting the role of phagocytosis, proteosomes, TAP, and chaperones
Details of Exogenous Antigen Path
- Detailed explanation of the pathway for processing and presentation of exogenous antigens. This explanation must include how APCs capture these antigens via phagocytosis or receptor-mediated endocytosis, how these antigens are processed, and the subsequent loading onto MHC class II molecules
Details of Endogenous Antigen Path
- Detailed explanation of the pathway for processing and presentation of endogenous antigens. Include how these antigens are generated, how they are transported, the role of TAP, and their eventual association onto MHC class I molecules for subsequent recognition
Summary: Features of Antigens Recognized By T Cells
- Detailed description of the features and characteristics required for T-cell recognition of various antigens This focuses on how these T-cells recognize these antigens. Include a list of the different antigens and whether they are exogenous or endogenous
Are Hapten Recognized by T Cells?
- Role of hapten-specific B cells and how they bind to antigens via hapten determinants
- Explanation of how hapten-carrier conjugates are processed and presented to helper T cells. This will include recognizing different epitopes within the carrier complex and the antigen.
- Importance of hapten and carrier being physically linked to activate an effective cellular immune response.
On Your Own: Thought Questions
- Summarize the process of antigen presentation to cells of the immune system. Consider different pathways, and highlight the key steps involved in each process.
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Description
Test your knowledge on key concepts of immunology, focusing on MHC molecules, antigen recognition, and the distinction between immunogens and antigens. This quiz covers essential characteristics of T cells and B cells, as well as the significance of polymorphism in immune responses.
