Overview of Immunology. Evolution CORE CONCEPTS IN IMMUNOLOGY. Cliona O Farrelly
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1 Overview of Immunology Cliona O Farrelly Professor Comparative Immunology, School of Biochemistry & Immunology & School of Health Sciences cliona.ofarrelly@tcd.ie CORE CONCEPTS IN IMMUNOLOGY 1. Identification & Discrimination (harmful and harmless microbes/ harmful & harmless self) 2. Tolerance of harmless foreign antigens: commensal, foetal, dietary, 3. Mechanisms for Expansion, Amplification, Proliferation, Action, Resolution of response against harmful stimuli 4. Immunisation 5. Dysregulation or inappropriate immunoregulation: disease chronic infection chronic inflammation autoimmunity allergy Cancer 6. Immunotherapy Evolution 1
2 Evolution & Time (Surface area:~70 m2 ) Gut Microbiome 1-2 kilos (Surface area:~2000 m2 ) Firmicutes: 250 genera Lactobacillus, Mycoplasma, Bacillus, Clostridium spp Bacteroidetes 20 genera 1013 cells in the human body 1014 bacteria 2
3 Genitourinary Tracts Infection Across Epithelial Barriers Important immunological role for epithelial cells Breaching the Epithelium Bacteria Escherichia coli (E.coli) Salmonella typhi Staphylococcus aureus Mycobacterium tuberculosis Bad Bugs 3
4 Bad Bugs Viruses Influenza Virus Human Immunodeficiency Virus Hepatitis A, B & C Measles Mumps Chicken Pox Foot & Mouth The Power of Immunisation Small Pox : Deadly Killer Virus Now eradicated as an infection from the world Successful Vaccines: Small pox polio measles, mumps, rubella. Main Features of Immunity Recognition Specificity Infectious Diseases without a vaccine common cold flu HIV hepatitis C foot and mouth Cancer Autoimmune Disease Response Speed Accuracy Regulation Memory SPECIFICITY MEMORY 4
5 Systemic Response Antimicrobial peptides Local infection Tolls in Charge Scientific American O Neill, 2005 Pattern Recognition & Immune Response Immune Organs Innate Immunity: Pathogen Associated Molecular Patterns Pathogen Recognition Receptors Adaptive Immunity: T & B Cells; T Cell Receptors Antibodies Bone Marrow (Bursa) Thymus Lymph nodes Spleen Peyer s Patches (Gut) (Liver) (Uterus) 5
6 Innate Immunity: Phagocytes monocytes granulocytes NK Cells Adaptive: B lymphocytes antibodies T lymphocytes Immune Cells Immune Cells Differentiate from Haematopoietic Stem Cells Bone marrow is primary site of haematopoiesis in the adult human Haematopoiesis : Stem cell Lymphoid lineage Myeloid lineage Cytokines: Messenger Proteins - Activation of Immune Mechanisms/Inflammation Immune Mechanisms - Chemotaxis - Recruitment/Differentiation of Immune Cells - Immunoregulation IL10 & TGFβ: key regulatory cytokines 6
7 Immune Mechanisms Opsonisation Circulating Detector Molecules Immune Mechanisms Phagocytosis Immune Mechanisms Killing altered self Natural Killer Cells Kill: - Virally infected cells - Transformed cells Innate Immunity Detection amplification Cytokine production Opsonisation killing Recruitment killing Resolution Adaptive Immunity More specific detection 7
8 Adaptive Immunity: Lymphocytes Adaptive Immunity - Specific Receptors T lymphocytes help/regulate (cytokines) kill Immunoglobulin Surface (B Cells) Circulating - abies B lymphocytes plasma cells produce antibody T Cell Receptors coded for by rearranging genes: possible specificities Evolution of Immune Mechanisms Systems Immunology A network-based analysis of systemic inflammation in humans. Steve E. Calvano*, et al. Nature 2005;437: humans hospitalised - Endotoxin infused in 4 - PBMCs taken x 6 - Gene expression analysed Gary W Litman & Max D Cooper NATURE IMMUNOLOGY JUNE
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