PHGY 209 Immunology Lectures 1-2 2024 PDF

PHGY 209 IMMUNOLOGY Dr. Melissa A. Vollrath [email protected] McMed 1234 Undergraduate Student Course Assistants Sofia Arnet Tal Shukhmeister [email protected] tal.sh...

PHGY 209 IMMUNOLOGY Dr. Melissa A. Vollrath [email protected] McMed 1234 Undergraduate Student Course Assistants Sofia Arnet Tal Shukhmeister [email protected] [email protected] Discussion Practice Email Board Questions IMMUNOLOGY LECTURE 1 The Immune System Pathogens The Immune System is Enormous – Scattered throughout the body – Connected by blood and lymph Role in Protection – Protects the entire body, at all times – From Pathogens: Bacteria, Viruses, Parasites – From altered body cells: Cancer No System Escapes its Surveillance; It Can Turn on Us Cancer – Autoimmune Disorders Cells – Foreign tissues: Transplant or Graft  Strategies for Protection – Two Prongs of the Immune System Non-Specific/Innate Immunity Specific/Adaptive Immunity Born with both systems Non-Specific/Innate Specific/Adaptive First-line of defense DOES NOT need to recognize the pathogen REQUIRES recognition of the pathogen Same response each time it sees a pathogen Faster response with second exposure to the pathogen Strategies for Protection Non-Specific/Innate Immunity Specific/Adaptive Immunity How does the immune system recognize something as “foreign”? How is the immune system organized? What cell types are involved? How do the cells develop? What are their functions? Examples: Immune system dysfunction – SCID and AIDS Harnessing the power of the immune system – Immunization Discoveries in Science Accidents of nature Leaps of faith Serendipity Penicillium chrysogenum Alexander Fleming Staphylococcus aureus Penicillin G (benxylpenicillin) Severe Combined Immune Deficiency Syndrome (SCID) Severe Combined Immune Deficiency Syndrome (SCID) David Vetter born, 1971 HIV causes loss of Thelper Cells  Smallpox and Vaccination Smallpox killed over 300 million people, lasted for over 3,000 years and killed 30% of those who contracted it Pharaoh Ramses V died of smallpox in 1157 BCE London, 1796, Dr. Edward Jenner Ali Maow Maalin, a hospital cook in Merca, Somalia, was the last person to contract smallpox in the wild, in 1977. He survived with treatment. Two other cases were acquired by accidental laboratory exposure in 1978: one died. These were the last known cases of smallpox. WHO: “Smallpox eradicated in 1980” Components of the Immune System Lymphoid Organs – Primary Lymphoid Organs Sites where stem cells divide, and immune cells develop Secondary Lymphoid Organs Sites where most immune responses occur Immune Cells – Leukocytes Secretions of Immune Cells Primary Lymphoid Organs Sites where stem cells divide and where immune cells develop Bone Marrow (Yolk Sac and Fetal Liver in Embryo) Blood cells are produced here: B-cells and Immature T-cells Site Where B-Cells Mature Thymus Located above the heart Contains T cells, scattered dendritic cells, epithelial cells, and macrophages Site Where T cells mature Atrophies after maturity BURSA of Fabriciu s Secondary Lymphoid Organs Sites where most immune responses occur Lymph Nodes Scattered throughout the body Filter microbes Macrophages in nodes phagocytize microbes that enter lymph Spleen Largest lymphoid organ Removes microbes and old erythrocytes Lymphoid Nodules Tonsils Peyer’s Patches and MALT (Mucosal-Associated Lymphoid Tissues) Appendix Immune Cells Travel in Blood and Lymph Lymph Node © Dr. Gopal Murti/SPL/Science Source Immune Cells are Leukocytes/White Blood Cells Lymphoid Cells Cytotoxic T-Cells CD8+ T Cells Helper T-Cells CD4+ B Cells Regulatory T-Cells CD4+ NK Cells Macrophage Dendritic Cells Myeloid Cells Immune Cells are Leukocytes/White Blood Cells Eosinophils - Destroy parasites Basophils - Release a variety of chemicals histamine, prostaglandins Mast Cells - Release chemicals, histamine Neutrophils - Phagocytes Monocytes – Become Macrophages and Dendritc Cells (Phagocytes) Lymphocytes – B lymphocytes T lymphocytes (TH and TC) Cells Mediating Immune Responses Name Site Produced Functions Leukocytes (white blood cells) Neutrophils Bone marrow Phagocytosis Release chemicals involved in inflammation (vasodilators, chemotaxins, etc.) Basophils Bone marrow Carry out functions in blood similar to those of mast cells in tissues (see below) Eosinophils Bone marrow Destroy multicellular parasites Participate in immediate hypersensitivity reactions Monocytes Bone marrow Carry out functions in blood similar to those of macrophages in tissues (see below) Enter tissues and transform into macrophages Lymphocytes Mature in bone marrow (B cells and NK cells) Serve as recognition cells in specific immune and thymus (T cells); activated in peripheral responses and are essential for all aspects of these lymphoid organs responses B cells Initiate antibody-mediated immune responses by binding specific antigens to the B cell’s plasma membrane receptors, which are immunoglobulins Upon activation, are transformed into plasma cells, which secrete antibodies Present antigen to helper T cells  Cells Mediating Immune Responses Name Site Produced Functions Leukocytes (white blood cells) Cytotoxic T cells CD8 + cells Bind to antigens on plasma membrane of target cells (virus- infected cells, cancer cells, and tissue transplants) and directly destroy the cells Helper T cells CD4 + cells Secrete cytokines that help to activate B cells, cytotoxic T cells, NK cells, and macrophages NK cells Bind directly and nonspecifically to virus-infected cells and cancer cells and kill them Function as killer cells in antibody-dependent cellular cytotoxicity (ADCC) Plasma cells Peripheral lymphoid organs; differentiate from B cells Secrete antibodies during immune responses Macrophages Bone marrow; reside in almost all tissues and organs; Phagocytosis differentiate from monocytes Extracellular killing via secretion of toxic chemicals Process and present antigens to helper T cells Secrete cytokines involved in inflammation, activation and differentiation of helper T cells, and systemic responses to infection or injury (the acute phase response) Dendritic cells Almost all tissues and organs; microglia in the central Phagocytosis, antigen presentation – PROFESSIONAL APCs nervous system Mast cells Bone marrow; reside in almost all tissues and organs; Release histamine and other chemicals involved in inflammation differentiate from bone marrow cells  Bacteria Bacteria Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Ability of the body to defend against microbes and other foreign substances without recognition of the invading pathogen First Line of Defense Physical Barriers Second Line of Defense Cellular Factors Humoral Factors First Line of Defense Barriers to entry & creating an unpleasant environment for microorganisms Skin – Water resistant, prevents entry of foreign substances Additional Physical and Mechanical Barriers - Tight Junctions in Epithelia Mucus Hair and Cilia Chemical and Microbiological Barriers - Secretions Sebum, Lysozyme, Gastric Juice Normal Flora NB: Just for your information, not for exam NB: Just for your information, not for exam Second Line of Defense Second Line of Defense – Innate Immunity NO MEMORY Humoral Factors Inflammation and Fever Antimicrobial Substances Acute Phase Reactants: C-Reactive Protein, Complement, Cytokines Interferons Cellular Factors Phagocytic Cells neutrophils, macrophages, dendritic cells Cells with inflammatory mediators basophils, mast cells, eosinophils Natural Killer Cells Second Line of Defense – Innate Immunity NO MEMORY Humoral Factors Inflammation and Fever Antimicrobial Substances Acute Phase Reactants: C-Reactive Protein, Complement, Cytokines Interferons Cellular Factors Phagocytic Cells neutrophils, macrophages, dendritic cells Cells with inflammatory mediators basophils, mast cells, eosinophils Natural Killer Cells Inflammation – Non-Specific Response to Tissue Damage 4 Distinct Signs and Symptoms Redness Heat Pain Swelling 3 Stages of Inflammation 1. Vasodilation* 2. Emigration of Phagocytes 3. Tissue Repair *Widening of blood vessels allows more blood flow to the site *Increased permeability of capillaries allows substances to go to the damaged site Humoral Substances Discourage Microbial Growth or Spread of Pathogen Interferons (antiviral proteins) Complement Iron-Binding Proteins  Type I Interferon Prevents Viral Replication Virus Infected Cell  Type I Interferon Prevents Viral Replication Virus Infected Cell Type I Interferons  Type I Interferon Prevents Viral Replication Virus Infected Cell Type I Interferons Type I interferon receptor Uninfected cell  Type I Interferon Prevents Viral Replication Virus Antiviral Infected Cell Type I protein Interferons Type I interferon receptor Uninfected cell  Type I Interferon Prevents Viral Replication Virus No replication Newly infected cell Antiviral Infected Cell Type I protein Interferons Type I interferon receptor Uninfected cell Humoral Substances Discourage Microbial Growth or Spread of Pathogen Interferons (antiviral proteins) Complement – A large family of plasma proteins with multiple functions 30 different proteins participate in the cascades C3b Iron-Binding Proteins Complement Non-Specific/Innate Immunity Specific/Adaptive Immunity X Opsonization – prepare for eating Function of Complement C3b as an Opsonin C3b – plasma protein that sticks to bacteria this opsinization, makes the bacteria more recognizable to phagocytes Humoral Substances Discourage Microbial Growth or Spread of Pathogen Interferons (antiviral proteins) Complement Iron-Binding Proteins – Transferrin IMMUNOLOGY LECTURE 2 [email protected] [email protected] [email protected] Summary of Lecture 1 - Immunology The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense - Cellular and Humoral Factors Summary of Lecture 1 - Immunology The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense - Cellular and Humoral Factors Summary of Lecture 1 - Immunology The Immune System - Scattered and Large Mast Cell - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types DC M⌽ Innate Immune System - First Line of Defense - Second Line of Defense NK TH TC - Cellular and Humoral Factors B Summary of Lecture 1 The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense - Cellular and Humoral Factors Summary of Lecture 1 The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense - Cellular and Humoral Factors Summary of Lecture 1 The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense - Cellular and Humoral Factors Summary of Lecture 1 - Immunology The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary - Secondary Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense - Cellular and Humoral Factors Summary of Lecture 1 - Immunology The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary Complement Protein - Secondary C3b Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense Interferon - Humoral and Cellular Factors Summary of Lecture 1 - Immunology The Immune System - Scattered and Large - Connected by Circulatory and Lymphatic Systems Lymphatic Organs - Primary Complement Protein - Secondary C3b Immune Cell Types and Secretions Innate Immune System - First Line of Defense - Second Line of Defense Interferon - Humoral and Cellular Factors Second Line of Defense – Innate Immunity NO MEMORY Humoral Factors Inflammation and Fever Antimicrobial Substances Interferons Cellular Factors Natural Killer Cells Phagocytic Cells neutrophils, macrophages, dendritic cells Cells with inflammatory mediators basophils, mast cells, eosinophils Natural Killer Cells (NK Cells) Lymphocytes that target virus-infected cells and cancer cells Like Cytotoxic T cells they attack and kill target cells directly after binding to them Unlike Cytotoxic T cells, they are NOT antigen-specific NK cells do not need to recognize a specific antigen Release chemicals that lead to death of infected or abnormal body cells* *Cells not expressing MHC-I MHC Class 1 proteins are expressed on all normal, “Altered” or absent MHC Class 1 proteins cannot nucleated body cells. These are recognized by the stimulate the negative signal. The NK cell is activated NK cell and the NK cell will not kill the normal cell. and releases agents that kill the cell. Normal Infected Body Cell Body Cell Lacks Normal MHC I Phagocytes Recall that old red blood cells are phagocytosed in the spleen. Phagocytes - Non-specifically engulf microbial invaders Types Fixed-Tissue Macrophages – already in the tissues Neutrophils Neutrophils – will be recruited to the site of injury Monocytes – become Macrophages and Dendritic Cells DC M⌽ Monocytes Macrophage contacting and preparing to engulf microbial invaders © Eye of Science/Science Source Phagocytosis and intracellular destruction of a microbe Microbe in ISF Steps: Adherence, Ingestion, Digestion, Killing Microbe in ISF Debris & Signals How Does the Phagocyte Recognize Microbes? – Detects unique, conserved structures that are essential to microbial physiology (molecular signatures of infection) – Pathogen-Associated Molecular Patterns (PAMPs) – Lipopolysaccharide (LPS) of gram-negative bacteria – Peptidoglycan (PGN) of gram-positive bacteria – PAMPS are recognized by immune system receptors called Pattern Recognition Receptors (PRR) found on the surface of the macrophage: Toll-Like Receptors Toll-Like Receptors (TLRs) A family of highly conserved transmembrane receptors Essential for microbial recognition via PAMPs Extracellular domain for recognition of pathogens Intracellular signaling domain Flagellin Peptidoglycans Lipopolysaccharides Lipoproteins dsDNA Downstream Macrophage Signals  This starts the process of Inflammation Neutrophil Inflammation - Non-Specific Response to Tissue Damage 3 Stages of Inflammation 1. Vasodilation* 2. Emigration of Phagocytes 3. Tissue Repair Emigration of Phagocytes Chemotaxis – Chemically stimulated movement of phagocytes Chemokines/Chemoattractants Chemicals that attract phagocytes Neutrophil Margination – sticking to endothelial cell Diapedesis – Phagocytes move across capillary wall  Specific Role of Neutrophils in Inflammation Neutrophils Die in the Process of Killing Bacteria NETs – Neutrophil Extracellular Traps are made of processed chromatin bound to granular and selected cytoplasmic proteins which Neutrophil come from the lysed neutrophils. Pus is produced Pus is a mixture of dead bacteria and neutrophils NETs – Neutrophil Extracellular Traps HEALTH 22 October 2015  Antigen-Presenting Cells* and dendritic cells Neutrophil *APCs Link Innate and Adaptive Immunity  Antigen-Presenting Cells* and dendritic cells Neutrophil *APCs Link Innate and Adaptive Immunity Term: Antigen Immunogen – material that induces an immune response Allergen Ligand Antigen: antibody generator Can be the whole cell or a part of a cell Can be non-microbial Pollen Egg whites Incompatible blood cells Transplanted tissues Epitope: The part of the antigen that is recognized by the antibody Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Via Antigen Presentation by Phagocytes Host Defenses Non-specific/Innate Immunity Specific/Adaptive Immunity Mediated by Antibodies or Cells Humoral – Antibody-Mediated Immunity Involves B Lymphocytes Transform into plasma cells Synthesize and secrete antibodies Memory B Cells Cell-Mediated Immunity Involves Cytotoxic T cells Kill infected body cells, cancer cells, foreign cells The Major Histocompatibilty Complex (MHC) Recall, Natural killer killed cells with altered or missing MHC I on its surface. Two (2) molecular classes – MHC I expressed on all nucleated cells (HLA-A, HLA-B, HLA-C) – MHC II expressed on antigen-presenting cells (HLA-DP, HLA-DQ, HLA-DR) – Only identical twins have the same MHCs on their cells Human Leukocyte Antigen Complex https://www.blood.ca/ The Major Histocompatibilty Complex (MHC) MHC I – on all nucleated cells MHC II – on all Antigen-Presenting Cells Macrophages, Dendritic Cells, B-Cells The Major Histocompatibilty Complex (MHC) Recall, Natural killer cell knew which cells to kill due to an altered or missing MHC-1 on its surface. Two (2) molecular classes – MHC I expressed on all nucleated cells (HLA-A, HLA-B, HLA-C) – MHC II expressed on antigen-presenting cells (HLA-DP, HLA-DQ, HLA-DR) – Only identical twins have the same MHCs on their cells T-cell receptors recognize antigens only when they are associated with MHC II proteins This is part of the antigen presentation process Antigen Presenting Cells (APCs) Present Exogenous Antigens with MCH II STEPS: Ingest antigen Digestion into peptide fragments Synthesize and package MHC-II molecules Bind peptide fragments to MHC-II Insert antigen–MHC-II complexes on plasma membrane Adaptive Immune Response (Acquired, Specific) Antigen Characteristics: Reactivity - Antibody binds specifically to the antigen that provoked it Immunogenicity – Can provoke an immune response by stimulating antibody production to that antigen Antigen Presenting Cells (APC) – (MHC II + antigen) – Dendritic cell / “Professional APC” – Macrophage – B lymphocyte (B cell) Adaptive Immune Response (Acquired, Specific) Antigen Characteristics: Reactivity - Antibody binds specifically to the antigen that provoked it Immunogenicity – Can provoke an immune response (production of antibody specific to that antigen) Antigen Presenting Cells (APC) – (MHC II + antigen) – Interdigitating dendritic cell / “Professional APC” – Macrophage – B lymphocyte (B cell)  Specific/Adaptive Immunity Ability of the body to defend against specific microbes and foreign substances – Involves MEMORY for previously encountered antigens B Cells and T Cells are involved B and T Lymphocytes must recognize the specific foreign material to be attacked. Any molecule that can trigger an adaptive immune response against itself or the cell bearing it is called an antigen.  Specific/Adapive Immunity Specific/Adaptive Immunity Ability of the body to defend against specific microbes and foreign substances – Involves MEMORY for previously encountered antigens B Cells and T Cells are involved A typical adaptive immune response can be divided into three stages: Recognition of an antigen by lymphocytes Lymphocyte activation Attack launched by the activated lymphocytes and their secretions  Specific/Adaptive Immunity Ability of the body to defend against specific microbes and foreign substances – Involves MEMORY for previously encountered antigens B Cells and T Cells are involved Humoral A typical – Bimmune adaptive Cells response can be divided into three stages: Transform into plasma cells and produce and secrete antibodies The encounter Use and and Antibodies recognition of an antigen Complement to kill by lymphocytes Lymphocyte activation Cell-Mediated The attack launched–byCytotoxic T lymphocytes the activated Cells kill infected and their cells secretions Attack infected body cells, cancer cells, foreign cells Cytotoxic T-Cells (TC) Origins of B Cells and T Cells Origins of B Cells and T Cells BONE MARROW Multipotent uncommitted Hematopoietic Stem Cell Myeloid Lymphoid Stem Cell Stem Cell Partial differentiation maturation Immature Mature T Cell B Cell THYMUS SECONDARY LYMPHOID ORGANS  THYMUS SECONDARY LYMPHOID ORGANS B Cells T Cells Activation by antigen B Plasma Cells Antibodies Activation maturation by antigen Mature Helper TH TC TC T Cell Mature Cytotoxic T Cell Activation by antigen TH T Cells Encounter and Recognition Antigen Antigen B Cell Helper T Cell (T H) Cytotoxic T Cell (TC) B TH CD4+ TC CD8+ Activation Cytokines Cytokines + + TH1 TH2 Plasma Cells Antibodies Attack Guide phagocytes, Directly attack complement and NK cells antigen-bearing cells to attack antigen-bearing cells or to neutralize free antigen  T Cell T Cell Receptor MHC-II + Peptide Antigen Presenting Cell Co-Reception Required B7 – CD28 along with MHC-II + Peptide – TCR Checkpoint Inhibition All biological processes need “shut-off” controls In immune response this involves displacement of CD28 from B7 by CTLA4 or PD-1 Checkpoint Inhibition All biological processes need “shut-off” controls In immune response this involves displacement of CD28 from B7 by CTLA4 or PD-1 PHGY 209 Midterm Exam DATE: Tuesday, October 8, 2024 TIME: 7:00 - 8:30 pm LOCATION: TBA – see myCourses the morning of the exam FORMAT: 35 MCQs (~2-3 MCQs/lecture) CONTENT: body fluids, transport mechanisms, blood and immunology NB: Tutorial with Dr. Vollrath Thursday, Oct. 12 from 6:00-7:00 pm in Stuart Bio S1/3.  PHGY 209 Midterm Exam - Bring your McGill ID Card. You must show it at the exam; you will not be permitted to write the exam without it. - Bring Pencils (HB 2) and Erasers - Students may bring their own Dictionary: TRANSLATION ONLY (to be checked by the Invigilators) - Students may bring a Calculator: NON-PROGRAMMABLE ONLY (to be checked by the Invigilators)