Adaptive Immunity - Macleod 2024 PDF

Outsmarting the bug: Adaptive immunity 2X Fundamental topics in Biology Megan MacLeod MacLeod group: communication enables immune memory Pubic engagement project and App MacLeod Group 2020 T cells and B cells Influenza in lung after specific CD4 TInfection- influenza...

Outsmarting the bug: Adaptive immunity 2X Fundamental topics in Biology Megan MacLeod MacLeod group: communication enables immune memory Pubic engagement project and App MacLeod Group 2020 T cells and B cells Influenza in lung after specific CD4 TInfection- influenza infection altered cells epithelial cells Aims of talk: at the end of this lecture you should know What adaptive immunity is Which cells are part of the adaptive immune system How the adaptive immune system is activated What immune memory is Adaptive immune cells: cells that can respond specifically and in a tailored way Viruses Yeast & Bacteria Fungus Parasites  Main cell types of the adaptive immune system Cellular adaptive immunity Humoral adaptive immun CD CD8 CD T B 4 8 cell cell T T cell CD4 T cells cell CD8 T Antibody producing cells Helper T cells cells Killer T These cells are cells grouped together as they have unique receptors that enables them to recognise antigens take 2D Microbiology/Immunology, you’ll learn about some other types of T cell  Introduction to T and B cell receptors on’t know need to know the details of the Igα/β and CD3 molecules on this slide for 2X  B cells and T cells recognise different forms of antigen The BCR binds to native proteins/antigens Antigens that cross-link surface BCR provide optimal B cell activation No accessory cells required B cell T cells recognise processed antigen presented on MHC molecules on the CD8 surface of antigen presenting cells +T cell CD8 T cells see short peptides in MHC class I molecules CD4+ T cell CD4 T cells see longer peptides in Dendritic cell MHC class II molecules  Cellular immunity: Overview of T cell response 2. Activated DCs move to lymphoid organs carrying the pathogen 1. Pathogens infect tissues 3. DCs activate antigen specific T 6. T cells cells migrate to infected 4. T cells proliferate tissues to clear infection Some of these 5. T cells migrate out of the lymph node  T and B cell activation takes place in secondary lymphoid organs Dendritic cells enter lymph Paracortex or T cell nodes via afferent lymphatic zone: where DCs vessels from the tissue meet naïve CD4 and CD8 T cells B cell follicles: where B cells are found and respond to antigen  T cell activation requires three signals Signal 2 Costimulation T cell differentiation peptide- TCR MHC Signal 1 requires continued Cytokine receptor activation and Signal 3 sustained Inflammatory differentiation cytokine signals u take the 2D course, you’ll learn much more about costimulatory molecules Dendritic cells process antigen so that T cells can be activated 6. PRR triggering also causes the DC to 1. Pattern Recognition express high levels of Receptor (PRR) costimulatory triggering enhances molecules and make phagocytosis inflammatory cytokines 2. Bacteria are digested inside 5. PRR triggering causes endosomes the DC to migrate from the tissue to the draining lymph node 3. MHC molecules 4. MHC molecules containing inside endosomes meet peptides from pathogen are pathogen containing presented on the cell surface endosomes The perfect match - T cells with the right TCR are selected to respond peptide- MHC The selection of the T cells with the right TCR is called clonal selectio This can lead to clonal expansion  CD4 Thelper cell subsets Extracellu Viruses lar bacteria Fungi Intracellul ar Helminth Thelper 17 Thelper 1 bacteria worms Activate neutrophils Anti-viral response Thelper 2 and production of Enhance function of Enhance mucus response antimicrobial innate immune cells and wound healing via molecules via via cytokines - IFNγ cytokines e.g. Interleukin cytokines (IL-17 and and TNF  CD8 ‘Killer’ T cells Kill Kill cells infected tumour with viruses or cells intracellular bacteria Release inflammatory cytokines: help other immune cells dispose of the infected cell Release toxic granules that contain perforin to punch holes in the target cells and enzymes (granzymes) to trigger apoptosis in the target cell  Overview of B cell response - Part 1 2. Smaller antigen and pathogen products can drain into lymph nodes Dendritic cells can carry antigens and pathogens to the Lymph node and pass these onto B cells 1. Pathogens infect tissues B cell follicle 3. Smaller antigens are often picked up by macrophages that then pass the antigen onto B cells Lymph node  Overview of B cell response - Part 2 4a. Some activated CD4 T cell move towards the B cell follicle 4b. Activated B cells move towards the T cell zone They present peptides from the pathogen on MHCII to the activated CD4 T cell 5. The T and B cells move together to the B cell follicle that forms a Germinal Centre. B cells undergo Class We call these CD4 T cells: T follicular helper cells Switching  Overview of B cell response - Part 3 Germinal centre 6. B cells undergo rapid proliferation in the germinal centre 7. B cells undergo Somatic Hypermutation - changing nucleotides in their B cell receptor 9. These high affinity B cells present peptides from the 8. B cells compete for antigen on MHCII to follicular antigen - those with the helper CD4 T cells leading to highest affinity win! the formation of plasma cells and memory B cells Plasma cells Memory B cells The BCR undergoes somatic hypermutation and class switching in the germinal centre BCR on activated B cells BCR on naïve B cells Fab: Fragment of antigen binding Fc region Fc: fragment crystallisa ble Class switching Somatic hypermutation IgM IgD IgG IgE IgA Variable region: light chain Variable region: heavy chain  Class switching leads to a range of different types of antibody Antibodies are made by plasma cells IgM Ig IgE IgA G Low affinity antibody Most abundant in Involved in allergy Found at mucosal High avidity serum and anti-worm sites Activates the classical responses complement pathway are also IgD molecules but these are present at low concentrations in the serum  Humoral immunity: Antibodies protect the host in various ways Neutralise pathogen Activate complement Enhance phagocytosis (opsonisation) Antibody blocks the virus from binding to Complement component, C1q, is the its receptor on triggered This sets of the classical cells. Complement pathways. Receptor for the Fc part of Prevents infection Including formation of C3a and the Ab molecules helps C5a: increase inflammatory macrophages and response. neutrophils phagocytose And MAC formation! antigen  The end is just as important as the beginning Size of T/B cell response Recall Most T and B cells undergo 10 days apoptosis until peak A few cells remain as memory cells response Proliferation These respond more quickly Contraction providing superior immune protection 5 days to Memory peak We take advantage of the response functions of memory cells when we make vaccines Time after infection or vaccination  Summary: key learning points The adaptive immune cells are CD4 & CD8 T cells and B cells They express specialised receptors that enable them to recognise specific antigens/proteins/peptides T cells recognise processed antigens, B cells recognise native antigens B and T cells are activated in secondary lymphoid organs (lymph nodes and spleen) T cells protect the host by making cytokines and/or molecules that kill infected cells B cell get help from CD4 T cells to differentiate into plasma cells that make antibodies that protect the host Memory B and T cells form following an infection and can provide enhanced protection to the same pathogen  Related lectures Pathogens activate DCs to enable them to present antigen to T cells – See Sensing Danger lecture We use our knowledge of the adaptive immune system to improve vaccines – See Vaccination: design and mechanisms