PL1003 Topic 4 Lecture 4.3 Adaptive Immune Response PDF

The adaptive immune response Janine Coombes, [email protected]  Learning outcomes Define what is meant by the terms “antigen” and “epitope” Explain how T and B cells recognises their specific antigens. Explain the role of antigen presenting cells and MHC in activation of th...

The adaptive immune response Janine Coombes, [email protected]  Learning outcomes Define what is meant by the terms “antigen” and “epitope” Explain how T and B cells recognises their specific antigens. Explain the role of antigen presenting cells and MHC in activation of the T cell response. Identify the key effector functions of Th1 cells, Th2 cells and CD8+ T cells. List the key pathways through which antibodies protect against infection. Explain how immunological memory is generated. Illustrate the structure of an antibody 5 December 2 2 024 Key features of the adaptive immune response Specificity (highly specific to a particular pathogen or strain of pathogen) Diversity (capable of responding to almost infinite array of pathogens) Memory (responds more quickly and efficiently to subsequent exposures  vaccination) Self / Non-Self Discrimination (avoids autoimmune disease) What are antigens? Antigens are molecules recognized by the immune system (usually proteins), stimulating an immune response. Epitopes are the part of the antigen recognised and bound by antibody, or by antigen receptors on T and B cells Epitope Hemagglutinin protein:Epitopes of protein antigen Influenza virus antigen Antigen receptors Antibodies secreted by B cells recognize the same antigen as that B cell’s BCR. TCR= T cell receptor BCR= B cell receptor T cell B cell Antigens as keys to unlocking the immune response Antigen (epitope) BCR B cells Antigen binds to antigen receptors or antibody using a “lock and key” fit. A T or B cell will only become activated if it finds the correct key for the lock  specific antigen or cognate antigen. B cells With the help of T cells, proliferate and differentiate into plasma cells that secrete large amounts of antibodies (immunoglobulins). Express the B cell receptor (BCR) B cells differentiate into antibody- which recognises and binds a producing plasma specific antigen. cells B cells Antibodies are secreted versions of B cell receptors, and have the same antigen specificity. Antibodies are found in serum and other body fluids Bind and neutralise pathogens and enhance their uptake by phagocytes. Can activate complement to kill pathogens. Antibody structure: ImmunoglobulinComprise G (IgG) two heavy and two light chains with two identical antigen binding sites. The N-terminus of each heavy chain associates with one of the light chains to create two antigen-binding domains: Fab region The C-termini of the two heavy chains combine to form the Fc region : Complement activation Sela-Culang I, Kunik V and Ofran Y (2013) The structural basis of Interaction with other immune cells via antibody-antigen recognition. Front. Immunol. 4:302. doi: 10.3389/fimmu.2013.00302 Fc receptor binding Cell-mediated Immunity: T cells Also possess receptors on the cell surface that CD4+ recognise specific antigens: T cell receptor (TCR) Following antigen recognition, T cells proliferate and differentiate into different types of effector T cells. Cytotoxic T cells (CD8+) kill virus-infected and CD8+ tumour cells. Helper T cells (CD4+) help B cells to produce antibody and assist with activation of cytotoxic T cell responses and macrophage killing. Regulatory T cells (usually CD4+) suppress the T cells and B cells recognize antigen in fundamentallyDendritic cell -> professional different ways antigen presenting cell antigen B cells recognise T cells cannot directly antigens circulating MHC recognise free antigen. T freely, or attached to BCR antigen cell antigen receptors surface of microbes. recognise peptides TCR These are often large presented to them by Major molecules, and B cells Histocompatibility Complex recognise only a small (MHC) molecules. An portion or “epitope” on B cell accessory cell is required to the external surface of T cell process and present the the molecule. antigen to T cells. Dendritic cells process and present antigen to T cells in lymph nodes T cell Dendritic cell  Major Histocompatibility Complex (MHC) Cell surface molecules Main function is to present antigens to T cells Highly polymorphic owing to selective pressures on immune system to recognise highly variable and constantly mutating pathogens The most polymorphic genes in the human genome Human MHC is known as Human Leukocyte Antigen (HLA) complex. 5 December 2 13 024 Two types of MHC Molecule Class I MHC Expressed on all nucleated cells Recognised by CD8+ cytotoxic T cells Class II MHC Expressed on antigen presenting cells Recognised by CD4+ helper T cells  Co-stimulation T cell activation requires a “second signal” Comes from proteins on the surface of antigen presenting cells (e.g. DCs) called ”costimulatory molecules” Examples CD80, CD86 They are upregulated in response to infection or tissue damage  PRR! Helps to avoid T cell responses to harmless antigen. 5 December 2 15 024 There are different types of CD4+ helper T cells 5 December 2 16 024  Cytotoxic T cells https://www.westburg.eu/immunotherapy-for-cancer/active-immunotherapy/t-cell- Antigen specific T and B cells are rare Large numbers of T and B cells (4 x 10^11 T cells in adult human) But we need a lot –we want each to recognize a different antigenic epitope, so that that any non-self antigen - past present or future - can be recognised. This means only very few lymphocytes will recognise a particular antigen. Upon recognition of antigen, these rare antigen- specific cells will proliferate to generate a clone of cells bearing the same antigen receptor (clonal expansion). Immunological Memory It is important for the immune system to retain the ability to respond more quickly and efficiently to a previously encountered pathogen. This “immunological memory” is the basis of vaccination. Pathogen Pathogen Naïve T and B cells are exposure exposure Secondary activated by an infecting response Specific T cells pathogen They proliferate. Primary Most activated cells become response Larger response short-lived effector cells. Faster Some activated cells become response long-lived memory cells. Time