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Immunology BE433 Dr Christine Loscher Lecture 1 Overview: Innate and Adaptive Immunity Course Objectives • Review of Immune Response • Innate Immunity - Fixed defences - Pattern recognition - Complement • Adaptive Immunity - Dendritic cells – role in generation of the immune response - Humoral –...

Immunology BE433 Dr Christine Loscher Lecture 1 Overview: Innate and Adaptive Immunity Course Objectives • Review of Immune Response • Innate Immunity - Fixed defences - Pattern recognition - Complement • Adaptive Immunity - Dendritic cells – role in generation of the immune response - Humoral – B cells/antibody production - Cell mediated – T cells – antigen recognition and activation • Cell communication and signaling • Toll receptors • Manipulation of the immune response – developing therapeutics Overview • • • • The immune response Components of the immune system Innate immune response Adaptive immune response Components of the immune system • Originate in the bone marrow • • • • They then either - migrate to guard peripheral tissues - circulate in the blood - circulate in lymphatic system Figure 1-3 Figure 1-4 part 1 of 3 Figure 1-4 part 2 of 3 Figure 1-4 part 3 of 3 Figure 1-6 Lymphocytes: T and B cells. No functional activity until they encounter antigen. Can mount a specific immune response to almost any foreign antigen. Important Immune Sites • Peripheral lymphoid tissue. • Spleen: collects antigen from the blood • Lymph nodes: collects antigen from sites of infection • Mucosal-associated lymphoid tissue: collects antigen from epithelial surfaces of the body Innate Immunity • Conferred by elements with which you were born and which are available constantly and at short notice to deal with pathogens. • Macrophages and neutrophils provide the first line of defence • Innate cells play critical role in initiation and direction of the adaptive immune response • Innate immune response plays important role in initial control of infection/early response, as it takes 4-7 days for adaptive response to take effect • Most pathogens induce an immune response by activating the innate immune response • Adaptive response only needed when innate response fails to eliminate a pathogen • Does not generate immunological memory What do macrophages do when they meet a pathogen? Surface receptors Inflammation: heat, pain, swelling, redness Figure 2-1 Adaptive Immunity • Generation of antigen specific effector cells that target a specific antigen • Memory cells that prevent re-infection • Power of this response is due to the antigen specificity • Primary link – Dendritic cells • Ingest antigen and go to lymph tissue/nodes and present it to circulating lymphocytes • If lymphocytes see a self antigen – no response • If a foreign then T cell becomes activated and expands it numbers – clonal expansion. (MOVIE) Clonal expansion/selection • Important principle in adaptive immunity • Each lymphocyte bears a single type of receptor with unique specificity • Interaction with the appropriate foreign molecule leads to activation • The expanded/differentaited cells derived from the activated cell will also bear receptors of the same specificity • Lymphocytes bearing receptors for self molecules are deleted at an early developmental stage – should not respond to self. Figure 1-14 part 1 of 2 Figure 1-14 part 2 of 2 Specific cell surface receptor • Each lymphocyte carries cell-surface receptor of a single specificity • Generated by random recombination of variable receptor gene segments and pairing of distinct variable chains • B cell – immunoglobulin heavy and light chain • T cell – the 2 chains of the T cell receptor 2 signals required for lymphocyte activation Figure 1-21 Second signal • Co-stimulatory molecules • Dendritic cells, macrophages and B cells can express co-stim molecules and thus can activate naïve T cells • Antigen presenting cells (APC) • Dendritic cells - most important in initiating adaptive immune response Summary • Innate immune response – first line of defence – involved in early response – recognise common features of pathogens. • Adaptive immune response - induced only when innate response not enough to eliminate pathogen - recognises all pathogens specifically - generate memory to prevent re-infection