Immune system Overview 2.pdf

Overview of the Immune System: Innate and adaptive immunity Learning goals: To know and understand: • An overview of the main cellular and molecular components of the immune system • Main features of innate and adaptive immunity How does immunity affect us? What dou you know about immunity?...

Overview of the Immune System: Innate and adaptive immunity Learning goals: To know and understand: • An overview of the main cellular and molecular components of the immune system • Main features of innate and adaptive immunity How does immunity affect us? What dou you know about immunity? Immunity in health and disease Immunology: historical perspective Immunitas: The exemption of a community or an individual from obligations to the Roman state‐ they were “protected” Immunity: Protection against disease, more specifically, against infectious diseases Thucydides (5th century BC): description of people who recovered from a plague "the same man was never attacked twice" Immunology: historical perspective Variolation Vaccination Inhalation of dried crusts derived from smallpox pustules, China (16th century) Edward Jenner (1798) Louis Pasteur (1822-1895): immunization protects people against disease by exposing them to a harmless version of a microbe that is like the disease-causing pathogen, and the immune system learns to fight it. Immune System Integrated group of molecules and cells that are taking part in the induction and maintenance of a coordinated response against a potential threat to the body. Immune system Innate Adaptive (Jawed Vertebrates) Cellular External barriers Macrophages Neutrophils B lymphocytes T lymphocytes Humoral Eosinophils Innate lymph. cells/NK Molecules Molecules Complement Cytokines Antibodies Cytokines Innate Immunity: External barriers Physical (skin) Mechanical (cilia) Chemical (acid) Biological (enzymes) Innate Immunity: Cellular Phagocytic cells: Cytotoxic cells: Other granulocytes Innate Immunity: Humoral Cytokines: IL‐1, IL‐6, IL‐12, TNF‐α, Interferons Complement Other proteins: C reactive protein…. Innate Immunity: pathogen recognition • It recognizes molecular patterns through germline‐encoded receptors • Limited number (~103 receptors) Pattern Recognition Receptors (PRRs)  Pathogen‐Associated Molecular Patterns (PAMPs): LPS, CpG, Oligosaccharides, viral and bacterial DNA, etc.  Damage‐Associated Molecular Patterns (DAMPs): HSP, HMGB1, ATP, etc. PRRs do not recognize specific pathogens Innate Immunity: Functions  Clearance of the pathogenic agent  Priming of adaptive immunity  Tissue repair and remodeling Innate Immunity: functions Innate Immune System [fast and generic] 1st line of defense 1 2 1 Drives the type of adaptive immunity ‐ Control of some infections ‐ Keep the pathogen under control until adaptive immunity is mounted (4‐7 days) Adaptive Immunity [late, highly specific] 3 cooperation Effector phase Tissue repair and remodeling Adaptive Immunity: lymphocytes • T lymphocytes o They mature in the thymus. o Various subpopulations: CD4, CD8….. o T‐cell receptor for antigen recognition • B lymphocytes o They mature in the bone marrow and secondary lymphoid organs. o Antibody as antigen receptor and secreted Adaptive Immunity: antigen recognition Antigen Antigenic specificity Lymphocytic repertoire: 1011 clones (a different receptor per clone) Clonal selection • Individual B and T cells each have an individual specificity for a single antigen • When a B or T cell interacts with its specific antigen, it is selected and becomes activated • Activation results in a proliferation, expanding the clonal progeny • Each clone is reactive against the antigen that initially stimulated the original lymphocyte Adaptive Immune response: phases Adaptive Immune System Innate Immune System 1 Recognition Specificity 2 Activation  Expansion  Differentiation 3 Effector Effector Cells Memory: a classical hallmark of adaptive immunity – Primary response is initiated upon first exposure to an antigen • Memory lymphocytes are left behind after antigen is cleared – A second exposure to the same antigen re‐stimulates memory lymphocytes • Reactivation yields faster, more significant, better response Memory responses for innate immunity? Trained innate immunity • Some responses mediated by innate immunity increase upon repeated exposure • Functional, metabolic and epigenetic changes mediate new properties of “trained” cells. • Vaccination against some pathogens may improve responses against other microorganisms (not pathogen‐ specific) Immune tolerance It ensures that the immune system avoids destroying host tissue – Many of the random rearrangements used to create B and T cell receptors could be anti‐self – Tolerance helps to keep these anti‐self recognition molecules/cells from circulating in the bloodstream Properties of innate and adaptive immunity Adaptive Immunity Innate Immunity 1 Specific Generic [it recognizes common patterns] 2 Large repertoire Limited (1011 receptors) 3 Specific memory 4 Self‐tolerance 5 Develops during lifetime, slower, only in jawed vertebrates Trained immunity: non‐specific (discrimates self from foreign) Already present, faster, in all organisms Immune response and disease • Dysfunctions of immunity – Overly active or misdirected immune responses: allergies, autoimmunity – Immunodeficiency: Primary (genetic) or secondary (acquired) loss of immune function • Transplanted tissues – The body’s natural response to foreign tissue is to attack it and destroy it: we want to AVOID an immune response (rejection) • Cancer – The dangerous cells we want to target are our own self cells: Generally tolerated and hard to generate immunity against