T1 L1. An overview of immunology (MT) (1).ppt
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Module 204 Infection and Immunity An overview of immunology Dr Michael Tarzi Senior Lecturer & Honorary Consultant Immunologist Over-arching aims for the module • To ensure that adequate grounding in basic and clinical immunology for your future careers, so that you can confidently: – Recognise...
Module 204 Infection and Immunity An overview of immunology Dr Michael Tarzi Senior Lecturer & Honorary Consultant Immunologist Over-arching aims for the module • To ensure that adequate grounding in basic and clinical immunology for your future careers, so that you can confidently: – Recognise and understand immunologically-mediated diseases, their treatments and treatment toxicities – Request and interpret diagnostic immunology tests – Appreciate when/ where to refer and why – Understand scientific literature • These skills are relevant to virtually all roles in Medicine • To provide a ‘shop window’: – Intercalation – Most academic careers with a basic science component – Clinical careers with an Immunology component, especially: Allergy&Immunology, Infectious Diseases, Rheumatology, HIV, Haematology, Dermatology Module 204 Immunology • Lectures • – Basic immunology • Innate, adaptive, tolerance – Applied immunology • Mucosal immunology, cytokines, neuroimmunology, transplantation, immunomodulation – Clinical immunology • Classification of immunulogical • disease, autoimmunity, allergy, DTH immunodeficiency • Dry ELISA work 2.5 symposia – HIV infection – Inflammatory arthritis and C1 inhibitor deficiency – (cancer immunology – this year online resources+lecture) 2 tutorials – Autoimmunity/ ELISA – TB/ ELISpot Aims • This lecture will cover the following (in outline only, to approximately module 102 level): – Leucocytes involved in immunity – Communication between tissues in immunity – Antigen receptors • Adaptive: Antibody, T cell receptors • Innate: Pattern recognition receptors – The concepts of somatic hypermutation, clonal selection – Memory • Note that this is a revision lecture: all of these themes and more will be substantially developed throughout module 204 Learning outcomes • You should be able to: – Identify key leucocytes and know their key functions – Describe signalling strategies between leucocytes – Define innate and adaptive immunity – Describe adaptive immune receptors of T and B cells, compared to pattern recognition receptors – Describe in basic terms the processes of somatic recombination and clonal selection – Use this knowledge to explain primary vs secondary immune responses – Give examples of effector responses – Be able to outline the process of inflammation The main role of the immune system is to protect from infection Antigen •Anything the immune system responds to •Usually protein •Not necessarily ‘bad’ The main role of the immune system is to protect from infection Antigen •Anything the immune system responds to •Usually protein •Not necessarily ‘bad’ Antigen Receptor •Recognises the antigen •Fundamental basis of immunity •Basis of division into innate and adaptive Innate Adaptive The main role of the immune system is to protect from infection Antigen •Anything the immune system responds to •Usually protein •Not necessarily ‘bad’ Germline-encoded pattern-recognition receptors Antigen-specific T and B cell receptors Antigen Receptor •Recognises the antigen •Fundamental basis of immunity •Basis of division into innate and adaptive Innate Adaptive The main role of the immune system is to protect from infection Antigen •Anything the immune system responds to •Usually protein •Not necessarily ‘bad’ Antigen Receptor •Recognises the antigen •Fundamental basis of immunity •Basis of division into innate and adaptive Effector Mechanism •An action to respond to the antigen Innate Innate Adaptive Adaptive Myeloid lineage Name Appearance Function Phagocyto sis Neutrophil Eosinophil ?Helminth infections Myeloid lineage Name Appearance Function Monocyte (circulating) Macrophage (tissue) Phagocytosi s Antigen presentation Dendritic cell Antigen presentation Myeloid lineage Name Basophil (tissueresident counterpart= mast cell) Appearance Function ?Helminth infections Lymphoid lineage Similar size to RBC Little cytoplasm with few granules B cells: make antibody, antigen presentation T cells CD4: help other components of immunity CD8: kill infected cells T cells and B cells=ADAPTIVE IMMUNITY NK cells: actually INNATE lymphocytes Direct lysis of infected cells and antibody-dependent cellular cytotoxicity Communication: intercellular signalling Juxtacrine Communication: cytokines&chemokines • Cytokines are small proteins released by cells that have an effect on another cell – They are important for communication between cells of the immune system and between immune system cells and other cells and tissues • Chemokines are similarly defined, but – Different structure, receptors and nomenclature – Main role is temporal and spatial organisation of cells and tissues IL=interleukin IL-21 Number refers to order of discovery ....but some are named differently eg TGF-β, IFN-g TNF-α Antigen receptors • The receptor that cells use to recognise antigen is a key concept in immunology, and forms the basis of separating two immunological arms: innate and adaptive Key features of innate antigen receptors • Do not recognise antigen specifically – Pattern recognition receptors’ (PRRs) – Recognise ‘pathogen associated molecular patterns’ (PAMPS) • Genome-encoded • Not clonally distributed Manose binding ligand (MBL) Classical features of innate immune receptors/ defences, as per module 102 • Work quickly – first line of defence • Adaptive immunity takes more time to be activated • Unable to ‘learn’, as germline encoded and therefore cannot change – therefore no memory • All of these statements are still partially valid, but the reality is far more complex – see later lectures for more detail Key features of adaptive antigen receptors • Recognise antigen specifically • T cell receptor, B cell receptor (antibody) • Produced by random somatic recombination events between gene segments • Huge receptor diversity • Clonally distributed • Permit specificity and memory in immunity B cells B •B cell receptor (antibody) may be surface-bound or secreted •Recognises intact antigen The T cell receptor •T cell receptor is very similar to the B cell receptor •Only a surface receptor on CD4 and CD8 T cells •Recognises processed antigen in the form of linear peptides Generation of adaptive immune receptor by somatic recombination events T and B cell receptors are produced by random recombination events between V, (D) and J gene segments, producing a huge receptor diversity despite a small number of genes. The most useful receptors are selected after birth upon exposure to pathogens B Antigen processing pathways Clonal selection T and B cell memory (Y axis could also be number of T lymphocytes specific for antigen A or B) After primary infection, most clonally-expanded T and B lymphocytes die off; a few remain as long-lived memory cells Effector mechanisms: some examples • • • • • • • Barriers (skin, acid pH in gut etc etc) Cytokines Complement Phagocytosis (enhanced by opsonisation) Cytotoxicity (CD8 T cell, NK cell) Antibody-dependent cellular cytotoxicity Mast cell and eosinophil degranulation Effector mechanisms are shared between innate and adaptive immunity. Adaptive immunity is defined by its receptors not by its effector mechanisms CD8 T cells Acute Inflammation • Inflamito – setting alight • Cardinal features: hot, painful, red, swollen • Describes a process, but tells you nothing of the cause Blood vessel changes underlie the process •Vasodilatation •Adhesion molecules •Increased permeability The clinical features are therefore defined by an interaction between the pathogen and host immunity Module 204: Basic immunology • The concepts of module 102 hold true, but the detail needs development • General – Cellular traffic, homing and signalling – Cytokines and chemokines • Innate immunity – Receptor types – NK cells – Soluble mediators, particularly complement and interferons – Extended role of innate immunity in health and disease • Adaptive immunity – Somatic recombination – Antibody isotype details – Antigen processing – HLA system – CD4 T cell subtypes Module 204: Applied immunology • The application of basic immunology did not really feature in module 102 – How is immunological tolerance achieved? – How does the immune system work together to produce an immune response – How does an immunoassay work? – How do drugs affect the immune system? – Are there links between the CNS and immunity? – How do vaccinations work? – Mucosal immunity – Aging and immunity – Cancer and immunity Module 204: Clinical immunology • Clinical aspects of immunology did not really feature in module 102 – How do we classify immune-mediated disease? – Allergic diseases – Contact dermatitis – The immunology of transplantation – Autoimmune diseases – Immune-complex diseases – Immunodeficiency diseases – Symposia: rheumatoid arthritis, C1 inhibitor deficiency and HIV Books&Resources Core text for module = Male, D et al. Immunology. 8th ed. For quizzes and resources use: http://www.garlandscience.com/garlandsci ence_student/student_home.jsf?landing=s tudent …..Free to register