2024-07-10_Lecture 15_Immuno I - Intro Immunology I_Slides.pdf

Introduction to Immunology I: Cell and Organs of the Immune System Maria E Ramos Nino, PhD Professor Department of Microbiology, Immunology, and Pharmacology [email protected] 1 ...

Introduction to Immunology I: Cell and Organs of the Immune System Maria E Ramos Nino, PhD Professor Department of Microbiology, Immunology, and Pharmacology [email protected] 1 Recommended Books SAKAI: Supplementary Material Chapter Lectures Abbas, A; Lichtman, A; and Pillai, S. 1 11, 13 Basic Immunology. Any edition (6th 2 15, 17 edition). Elsevier. 2016 3 21, Abbas, A; Lichtman, A; and Pillai, S. Cellular and Molecular Immunology. 4 25 10th edition. Elsevier. 2018 4 27 Kaplan medical. Step 1. lecture Notes 5 39 2017. Immunology and Microbiology. USMLE. 6 41 FOCIS annual meeting: Couse in 7 43 Medical Immunology 8 45 11 47 9, 10 51 4  Immunity Traditional concept: Immunity refers to protection against infectious diseases Modern concept: Immunity is a function of which an individual recognizes and excludes antigenic foreign substances. It is normally beneficial, but sometimes, it is injurious https://www.creative-diagnostics.com/Infection-Immunity.htm 6 SOM.MKII.BPM3.12.1.6.I.IB.1 Define immune terms Beneficial Damaging 7 Abbas’ Immunology SOM.MKII.BPM3.12.1.6.I.IB.1 Define immune terms  Immunology and Microbiology: Chain of Infection Transmission Microbe Host Contact Infectious dose (ID) Host factors Vehicle Virulence factors - Innate immunity Airborne - Adaptive immunity Vector 8 SOM.MKII.BPM3.12.1.6.I.IB.1 Define immune terms  Immunology and Microbiology  Immune system evolved to protect multicellular organisms from pathogens Activities required for this protection: Recognition and response  Terms we need to be familiar with: Pathogen – something that causes disease Antigen – any foreign substance that binds specifically to an antibody or T cell receptor Epitope – portion of the antigen that is recognized by an antibody or T cell receptor https://courses.lumenlearning.com/wm-biology2/chapter/t-and-b-lymphocytes 10 / SOM.MKII.BPM3.12.1.6.I.IB.1 Define immune terms  Antigen Related Terms Terms we need to be familiar with (cont…..): Immunogen – a substance capable of eliciting an immune response All immunogens are antigens but not all antigens are immunogens (i.e. haptens) Hapten - a small molecule that, when combined with a larger carrier such as a protein, can elicit the production of 1 antibodies that bind specifically to it Carbohydrate NO IMMUNE RESPONSE IMMUNE RESPONSE 11 https://www.creative-diagnostics.com/Hapten.htm SOM.MKII.BPM3.12.1.6.I.IB.1 Define immune terms Antigen Factors in Immunogenicity Important to select targets for vaccines  Foreignness: Degree of foreignness; relative to phylogenetic distance  Molecular Size: Generally, > 100,000 Da  Chemical Composition: Greater complexity (heterogeneity) = greater immunogenicity Generally, proteins > carbohydrates > lipids Susceptibility to processing and presentation D-amino acids cannot be processed; poorly immunogenic  Adjuvant: BSA in mice; alum in humans Generally, increase persistence of antigen and innate response (inflammation, stimulation of APC and/or lymphocytes) 12 SOM.MKII.BPM3.12.1.6.I.IB.2 Determinants of immunogenicity Host Factors in Immunogenicity  Genotype of host: MHC gene products B cell receptors TCR  Dosage and Administration: Low doses may induce tolerance or fail to stimulate enough lymphocytes Boosters increase clonal selection Route: slow release is important for immune response: Subcutaneous > Intraperitoneal > Intravenous > Intragastrical oral route induce local mucosal immunity but not systemic immunity 13 SOM.MKII.BPM3.12.1.6.I.IB.2 Determinants of immunogenicity Figure A-2 14 SOM.MKII.BPM3.12.1.6.I.IB.2 Determinants of immunogenicity  Pre-existing (present at birth)  Responsive  Specific  Non-specific 16 SOM.MKII.BPM3.12.1.6.I.IB.3 Innate vs. Acquired immunity Two Arms of the Immune System 1. Innate Arm: Molecular and cellular mechanisms preformed and fully active (immediate reaction) Nonspecific: Distinguishes between self and pathogens but not specialized to distinguish small differences in the foreign particles Components: Barriers that protect host Skin, including its usual skin flora Mucous membrane Acidity of stomach Lysozymes in fluids… Phagocytic cells Antimicrobial peptides (interferons, complement) Temperature 17 SOM.MKII.BPM3.12.1.6.I.IB.3 Innate vs. Acquired immunity Two Arms of the Immune System 2) Acquired (adaptive) arm:  Develops in response to infection  Adapts to recognize, eliminate, and remember pathogen  Highly specific  Takes several days for this arm to become fully functional  Components:  cell-mediated immunity  antibody-mediated (humoral) immunity  Attributes: Antigenic specificity Antibodies can distinguish between 2 proteins that differ in only 1 amino acid Diversity Immunologic memory Self/non-self recognition 18 SOM.MKII.BPM3.12.1.6.I.IB.3 Innate vs. Acquired immunity Kuby’s Immunology 6th edition 19 SOM.MKII.BPM3.12.1.6.I.IB.3 Innate vs. Acquired immunity  Body Compartments that Participate in the Immune System  The bloodstream  The mononuclear phagocyte or reticuloendothelial system  The lymphatic system SOM.MKII.BPM3.12.1.6.I.IB.4 Body compartment that participate in immunity 21  Bloodstream Hematopoiesis – production of blood cells https://open.oregonstate.education/aandp/chapter/6-1-the-functions-of-the-skeletal-system/ 22 SOM.MKII.BPM3.12.1.6.I.IB.5 Hematopoiesis Hematopoiesis  All blood cells arise from Hematopoietic Stem Cells (HSC)  HSC Stem cells: -mother of all blood cells: lymphoid and myeloid elements -may self-renew  CFU-GEMM or CFU-L -can self renew or commit to progenitor cell  Progenitor: committed stem cells; limited self-renewal 1) Myeloid progenitors: granulocyte, macrophage, monocyte, erythroid, megakaryocyte, eosinophil, basophil 2) Lymphoid progenitors: lymphocytes 23 SOM.MKII.BPM3.12.1.6.I.IB.5 Hematopoiesis  Hematopoiesis HSC Myeloid progenitors: CFU-GEMM CFU-L Lymphoid progenitors:  Macrophage  Lymphocytes  Monocyte  NKs  Eosinophil  Basophil Granulocytes http://www.allthingsstemcell.com/wp-content/uploads/2009/02/hematopoiesis_simple1.png Agranulocytes: Lymphocytes and monocytes 24 SOM.MKII.BPM3.12.1.6.I.IB.6 Granulocytes vs. agranulocytes  https://veteriankey.com/innate-immunity-neutrophils-and-phagocytosis/ 25 SOM.MKII.BPM3.12.1.6.I.IB.6 Granulocytes vs. agranulocytes  Maranur 26 SOM.MKII.BPM3.12.1.6.I.IB.6 Granulocytes vs. agranulocytes What are these? Platelet Erythrocyte Eosinophil Lymphocyte Neutrophil Basophil Monocyte 27 SOM.MKII.BPM3.12.1.6.I.IB.6 Granulocytes vs. agranulocytes  28 SOM.MKII.BPM3.12.1.6.I.IB.6 Granulocytes vs. agranulocytes Hematopoietic Homeostasis  Erythrocyte Average life span: 120 days Phagocytosed by macrophages in spleen  WBC - LEUKOCYTES Life spans from 1 day to 20-30 years https://creativemeddoses.com/topics-list/necrosis-vs-apoptosis-six-major-differences/  Apoptosis – programmed cell death 29 SOM.MKII.BPM3.12.1.6.I.IB.5 Hematopoiesis Body Compartments that Participate in the Immune System  The bloodstream  The mononuclear phagocyte or reticuloendothelial system  The lymphatic system SOM.MKII.BPM3.12.1.6.I.IB.4 Body compartment that participate in immunity 30 Mononuclear Phagocyte System ( Reticuloendothelial System)  Network of connective tissue fibers and cells surrounding sda organs s Cell Mast  Inhabited by phagocytic cells – mononuclear phagocyte system –ready to attack and ingest microbes that passed the first line of defense Tissue sentinel cells 31 Body Compartments that Participate in the Immune System  The bloodstream  The mononuclear phagocyte or reticuloendothelial system  The lymphatic system SOM.MKII.BPM3.12.1.6.I.IB.4 Body compartment that participate in immunity 32 Lymphatic System  Provides an auxiliary route for return of extracellular fluid to the circulatory system  Acts as a drain-off system for the inflammatory response  Renders surveillance, recognition, and protection against foreign material 33 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs LYMPHOID TISSUES AND ORGANS  Lymphoid tissues and organs Primary Bone Marrow (B cells) and thymus gland (T cells) Development and maturation of lymphocytes Secondary Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s patches, mucosa- associated lymphoid tissue (MALT) Mature lymphocytes meet over pathogens 34 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs Kuby’s Immunology 6th edition https://www.slideshare.net/Pratheepsandrasaigar/primary-and-secondary-lymphoid-organs-64055020 35 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs  Primary Lymphoid Organs  Thymus T cell development and maturation Bi-lobed organ above heart - Surrounded by capsule and divided into lobules - Outer part of lobule is cortex, inner is medulla - Network of epithelial cells, dendritic cells, and macrophages Thymus will induce death of those T cells that can’t: - Recognize self-MHC molecules - Those that interact with MHC molecules too strongly  Function decreases with age (from puberty) http://www.wisemindbodyhealing.com/articles/research-resources/anatomy-the-thymus-gland/ 36 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs  Thymus Immature thymocytes (Cortex) Immunocompetent T cell (Medulla) Kuby’s Immunology 6th edition Maturation of T cells? Cytokine production? 37 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs Secondary Lymphoid Organs Lymph Nodes  3 regions: Cortex B cells mainly Primary follicle: un-activated lymphoid follicle Secondary follicle: activated o Germinal Centers Production of plasma and memory cells Paracortex Germinal center – area of activated B T cells, dendritic cells (APCs) cells that will proliferate, go through Activation of T cells somatic hypermutation and class Interaction of T and B cells switch Medulla Plasma cells secreting antibody and macrophages 38 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs Secondary Lymphoid Organs: Spleen  Lymphoid organ in upper left abdomen  Functions Filter blood Activation of lymphocytes from blood borne pathogen  Important in systemic infections  Structure: surrounded by a capsule Compartments: separated by a marginal zone  Red pulp Marginal zone: o Remove old or defective Antigens meet APCs erythrocytes and platelets Phagocytosis of antigen by innate  White pulp APCs meet o The periarteriolar lymphoid lymphocytes: sheet (PALS) with T-cells initiation of o Follicles with B lymphocytes immune response 39 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs Secondary Lymphoid Organs  Mucosa-Associated Lymphoid Tissue (MALT) Organized areas along digestive, respiratory, and urogenital tracts Bronchial-associated lymphoid tissue (BALT) -Tonsils, adenoids, Gut-associated lymphoid tissues (GALT) -Appendix, Peyer’s patches Skin-associated lymphoid tissue (SALT)  Pathogens are directly transferred across mucosa by Microfold cells (or M cells) 40 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs Cross-section of small intestine 41 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs  42 SOM.MKII.BPM3.12.1.6.I.IB.8 Primary and secondary lymph organs