MD137 Immunology Lecture 1 Introduction PDF

MD137 Immunology Lecture 1: Introduction Dr. Louise Horrigan Physiology [email protected] University ofGalway.ie Immunology Outline Lecture 1: Introduction to the immune system Lecture 2: Innate I...

MD137 Immunology Lecture 1: Introduction Dr. Louise Horrigan Physiology [email protected] University ofGalway.ie Immunology Outline Lecture 1: Introduction to the immune system Lecture 2: Innate Immunity Lecture 3: Adaptive Immunity Cell-mediated immunity Antibody-mediated immunity Lecture 4: Allergy & Autoimmunity Learning To learn: Functions of the immune system Objectives of Cells and tissues of the immune system Today’s Lecture Cytokines Concept of the evolutionary arms race between hosts and pathogens Historical milestones in the development of immunology Functions of immune system Infectious diseases Viruses, bacteria, parasites, fungi Promotes wound healing and tissue regeneration Elimination of cell debris Cancer fighting University ofGalway.ie Tissues of the Immune System Primary lymphoid organs Bone marrow Thymus Secondary/peripheral lymphoid organs Lymph nodes Spleen Mucosal immune system University ofGalway.ie Cells of the immune system Sentinels in the tissues Dendritic cells, macrophages, mast cells, Paneth cells Circulating cells (also present in tissues) Innate/Natural Immunity Neutrophils, monocytes, eosinophils, natural killer cells Adaptive/Acquired Immunity Lymphocytes T lymphocytes B lymphocytes University ofGalway.ie  Cells involved in innate and adaptive immunity Yamauchi, T., & Moroishi, T. (2019). Hippo pathway in mammalian adaptive immune system. Cells, 8(5), 398. Image available via license: CC BY Cytokines: Important effectors of immune function Small Proteins (5 – 20kDa) Secreted by cells and function in an autocrine and paracrine manner Bind to specific receptors on cells Interleukins (IL-1 – IL-22); Interferons (IFN-a, b, g); tumour necrosis factors (TNF-a, b); transforming growth factor-b (TGF-b) Each immune cell secretes a characteristic profile of cytokines that can determine that cell’s function Cytokines drive and orchestrate immune responses University ofGalway.ie Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45(2):27–37. doi:10.1097/AIA.0b013e318034194e Pathogens and hosts: the evolutionary arms race Survival of the fittest Immunocompetent hosts survive/successful microbes survive Through generations, evolutionary immune adaptation occurs in both hosts and pathogens University ofGalway.ie  Pathogens reproduce very quickly In every generation, mutations will occur While most may be killed by immune functions, strains of immuno- resistant pathogens will emerge Reproduction of immuno-resistant pathogens The host immune system can also evolve through genetic and epigenetic mechanisms https://evolution.berkeley.edu/evolibrary/article/medicine_02 Evidence of selective genetic pressure and immune adaptation: The Black Death Yersinia pestis spread through Europe th in 14 century Rroma gypsies had travelled from North India in 11th Century Genetically different from native Romanians Study showed immune adaptations had occurred in the Rroma, likely as a result of Yesrsinia pestis Laayouni H, Oosting M, Luisi P, et al. Convergent evolution in European and Toll-like receptors and cytokine Rroma populations reveals pressure exerted by plague on Toll-like receptors. responses Proc Natl Acad Sci U S A. 2014;111(7):2668–2673. doi:10.1073/pnas.1317723111 The basis of modern immunology Edward Jenner’s smallpox vaccine in 1796 Louis Pasteur’s hypothesis that disease is caused by microorganisms Cholera vaccine Elie Metchnikoff discovered phagocytosis in 1882 Paul Ehrlich predicted the existence of antibodies Charles A. Janeway proposed the theory of innate immunity (1989) and the pattern recognition theory University ofGalway.ie Edward Jenner Credited with the development of a vaccine against smallpox in 1796 WHO proclaimed disease eradicated in 1979  Jenner’s drawing of cowpox lesions Image attribution: https://commons.wikimedia.org/w/index.php?curid=40659361 Louis Pasteur (1822 – 1895) Introduced the concept that disease is caused by microbes Germ theory of disease Cholera, rabies vaccines Meanwhile…. Discovery of phagocytes in 1882 Elie Metchnikoff Experiments on larvae of starfish Established that phagocytosis is the first line of defence in infection Jointly awarded Nobel Prize in Physiology or Medicine with Paul Ehrlich in 1908 University ofGalway.ie Paul Ehrlich Predicted the existence of antibodies Introduced concept of discrimination between self and non-self Antitoxins If mice were subjected to slow and measured increase in toxin dose, mice could survive levels much higher than the lethal dose Toxin and antitoxin can bind Immunity can be transferred in the blood Summary of main points The immune system consists of a network of cells, tissues and soluble factors found throughout the body The immune system has functions that extend beyond the prevention of infectious disease The functions of the immune system are mainly underpinned by cells derived from haematopoietic stem cells in the bone marrow The immune system is continually evolving, through interactions with infectious agents Immunology is a relatively new discipline, with current cutting-edge research building on early work of pioneers including Jenner, Pasteur and others University ofGalway.ie