Immunology Lecture 3 2024 McGill PDF

IMMUNOLOGY LECTURE 3 [email protected] [email protected] [email protected]  Muscle & Autonomic Dr. Ragsdale Dec. 4, 5 PM Dec. 9, 5 PM...

IMMUNOLOGY LECTURE 3 [email protected] [email protected] [email protected]  Muscle & Autonomic Dr. Ragsdale Dec. 4, 5 PM Dec. 9, 5 PM Nervous System Change in Tutorial Schedule Instructor-Led Tutorials LECTURERS and TOPICS DATE TIME Location Dr. Vollrath Thursday, Sept. 5 5:30 – 6:30 PM McMed 522 Body Fluids Dr. Shrier PHGY 209 –Thursday, MAMMALIAN Sept. 12 PHYSIOLOGY 1 5:30 – 6:30 PM McMed 522 Transport Mechanisms Fall 2024 Dr. Vollrath Section 001: Monday, Wednesday, Thursday, and Sept. Friday26 from 9:35 5:30 – 6:30 – 10:25 AM –PM MCMED 522McMed 522 Blood Section 002: Monday, Wednesday, and Friday from 12:35 – 1:25 PM – ADAMS AUDITORIUM Dr. Vollrath Thursday, Course Oct. 3 Coordinators 5:30 – 6:30 PM McMed 522 Immunology Drs. Melissa Vollrath and Alvin Shrier Dr. Ragsdale Wednesday, Nov. 6 5:30 – 6:30 PM McMed 522 Nerve/Synapse Monday Wednesday Friday TOPIC LECTURER Dr. Cook August 28 Wednesday, Nov. 27 30 5:30 – 7:00 Course Overview, PM McMed 522 CNS Sensory/Motor/Cognitive Dr. Vollrath September 2 4 Homeostasis Dr. Ragsdale & Body 1 + 2 lectures Labour Day - No Class Wednesday, Dec. 4 5:30 – 6:30Fluids PM McMed 522 Muscle/Autonomic Nervous System 6 Transport Dr. Shrier Note: No new material9 will be introduced during tutorials. These sessions Mechanisms 2 lectures and are intended for clarification reinforcement of the subject matter covered in the lectures and readings. The tutorial sections are open to 11 13 Dr. Vollrath students from Sections 1 and 2. Blood 16 18 20 5 lectures When studying, make it a habit to write down difficult points that you do not fully understand. Come to the tutorial prepared to ask23 questions and to25discuss the answers 27 with the professors. Students Dr.studying Vollrath in 30 are especially English for the first time October 2 encouraged Immunology to attend tutorial sessions. 5 lectures In-Class Blood Tutorial 4 PHGY 209 Midterm Exam – In person 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 NOTE: Blood Tutorial in-class, Wednesday, Oct. 2 Immunology Tutorial Thurs., Oct. 3, 5:30-6:30 pm, McMed 522 Email questions to [email protected]  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) Summary of Lecture 2 - Immunology Non-Specific/Innate Immune System Second Line of Defense – Cellular Factors Natural Killer (NK) Cells – MHC Class I Phagocytic Cells Fixed-Tissue Macrophage – PAMPs and TLRs - Sends DANGER signal to recruit Neutrophils Neutrophils – margination, emigration and NET formation Dendritic Cells – Professional Antigen Presenting Cells (APCs) MHC Class II + Peptide (Antigen) on their surface travel to the regional lymph node: “Antigen Presentation” This links the Innate immune system to the Adaptive Immune System Non-specific/Innate Immunity Specific/Adaptive Immunity Summary of Lecture 2 - Immunology Specific/Adaptive Immunity Defends against specific microbes and foreign substances Involves memory for previously encountered antigens B and T Lymphocytes must recognize the specific antigen to be activated Helper T Cells TH Activate B Cells and Cytotoxic T Cells B Cells Transform into plasma cells to produce and secrete antibodies Humoral response: with Antibodies and Complement Cytotoxic T Cells TC Attack infected body cells, cancer cells, foreign cells Cell-Mediated response Macrophages Process and Present Antigen to a Helper T Cell APC TH  APC Encounter and Recognition MHC II Antigen Antigen Antigen Antigen B Cell Helper T Cell (TH) Cytotoxic T Cell (TC) B TH CD4+ TC CD8+ Activation + Cytokines Cytokines + TH1 TH2 Ç√çç√ç√ç√ç√ *Memory Cells Plasma Cells for each lymphocyte types will also be Antibodies TC TC produced Attack Humoral Cellular Guide phagocytes, Directly attack complement and NK antigen-bearing cells cells to attack antigen- bearing cells or to neutralize free antigen Events Required for the Activation of Helper T Cells 1. Specific Recognition MHC II + Peptide – T Cell Receptor APC 2. Co-reception CD28 – B7 3. Cytokine Release from APC Stimulates TH Cell MHC II B7 Antigen Coreceptors TH Receptor T-Cell CD28 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 Activation of B Cells in Secondary Lymphoid Organs Antigen MHC II APC B TH dead Bacteria on APC surface  B Cytokine Release Activates the B Cell B Cells can also Process and Present Antigen to Helper T Cells TH Antibodies, immunoglobulins will fight infection Serum Protein Electrophoresis Infection All the green peaks PLUS the red peak Serum Protein Electrophoresis Antibodies Gamma-globulin Infection All the green peaks PLUS the red peak Plasma Cell Antibody Structure Antibodies: part of a group of proteins called globulins, Immunoglobulins (Ig) Contain four polypeptide chains: Two identical Heavy chains Two identical Light chains Two distinct regions within heavy and light chains: Variable region = Antigen binding site FAB region antigen binding fragment, “hypervariable region” Constant region = Same in all antibodies of a class FC region crystallizable fragment Antibody Class – Determined by the Constant Region, FC 5 classes IgG - most numerous, cross the placenta IgA - found in MALT, breast milk IgM - first formed, complement activation IgD - prenatal IgE - allergy Antibody-Mediated Immunity Carried out by B cells B cells become activated in spleen, lymphoid nodule, or lymph node in the presence of a microbe Undergo clonal selection to produce: Plasma cells which secrete specific antibodies Memory cells which allow faster response if antigen is seen again Antibody-Mediated Immunity – Can be Actively or Passively Acquired Active – the person’s own immune system responds to a pathogen Long-lasting Protection – Memory Cells are involved Natural – Develops with natural exposure to an antigen Artificial – Develops with purposeful exposure to an antigen Passive – the person receives antibodies from another person or animal Temporary Protection - NO Memory Cells are involved Natural – examples: IgG From mother to fetus across the placenta IgA in Breast milk Artificial – example: Receive serum containing antibodies from person or animal Active Immunity Resistance due to the body’s contact with microorganisms, their toxins or other antigenic components from an infection (natural) or a vaccine (artificial) Vaccine: may consist of small quantities of living or dead pathogens, small quantities of toxins, or harmless antigenic molecules derived from the pathogen or its toxin General Principle: Exposure to the antigenic substance results in an active immune response that induces formation of memory cells required for rapid, effective response to future infections by the same pathogen Passive Immunity (natural) The direct transfer of antibodies from one person to another Examples: The fetus receives maternal IgG antibodies that cross the placenta Breast-fed children receive IgA antibodies in the mother’s milk (the intestinal mucosa is permeable to IgA antibodies during early life) ** These are important sources of protection for the infant during the first months of life, when their antibody-synthesizing capacity is relatively poor Passive Immunity (artificial) Example: Convalescent serum Antibody Functions Neutralizing Antigen Agglutination of Antigens Precipitation of Antigens Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity Antibody Functions Neutralizing Antigen Agglutinating Antigen Precipitating Antigen Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity Antibody Functions Neutralizing Antigen Agglutinating Antigen Precipitating Antigen Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity Antibody Functions Neutralizing Antigen Agglutinating Antigen Precipitating Antigen Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity Antibody Functions Neutralizing Antigen Agglutinating Antigen C1 Precipitating Antigen C1 Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity via cytotoxic T cells Complement Non-Specific/Innate Immunity Specific/Adaptive Immunity X Opsonization – prepare for eating Activation of Classical Complement Pathway by Antibody Binding to Bacterial Antigen Membrane Attack Complex Antibody Functions Neutralizing Antigen Agglutinating Antigen Precipitating Antigen Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity Antibody Tags Bacteria for Phagocytosis (functions as an opsin) Antibody Functions Neutralizing Antigen Agglutinating Antigen Precipitating Antigen Activating Complement Opsonization Antibody-Dependent Cellular Cytotoxicity via Natural Killer cells Antibody-Dependent Cellular Cytotoxicity Receptors for FC portion of an antibody are expressed on the surface of the NK cells A specific antibody binds to the target cell. The interaction between the antibody and the FC receptor activates the release of Granzymes and Perforin by the NK cell. Target for immunotherapy in cancer: generate antibodies for the tumor cells. Memory Cells Give Long-Lasting Protection Memory Cells Give Long-Lasting Protection Activating the lymphocytes that express the receptor for a specific antigen leads to the production of memory cells: B cells, TH Cells and TC cells that have receptors for that antigen. Memory cells expand the pool of lymphocytes with that specific receptor. We call this clonal expansion. Having more lymphocytes with this specific receptor allows the immune system to respond more rapidly if it sees the same antigen in the future. Rate of Antibody Production Following Initial Exposure to an Antigen and Subsequent Exposure to the same Antigen Antibody Concentration Rate of Antibody Production Following Initial Exposure to an Antigen and Subsequent Exposure to the same Antigen Antibody Concentration Time in months Rate of Antibody Production Following Initial Exposure to an Antigen and Subsequent Exposure to a Different Antigen Antibody Concentration Time in months Rate of Antibody Production Following Initial Exposure to an Antigen and Subsequent Exposure to a Different Antigen Antibody Concentration Time in months Plasma Cells Produce Antibodies FAB Region FC Region HEAVY CHAIN How are Antibodies Made Specific? FAB Region FC Region How do Lymphocytes Develop their Antigen Receptors? Lymphocytes Must Gain Immunocompetence - Develop Antigen Receptors Lymphocytes Must Gain Immunocompetence - Develop Antigen Receptors Pro-B Cell Pre-B Cell B Cell Plasma Call Mu Heavy Chain Mature Antibody + Surrogate B Cell Receptor Light Chain RAGs B-Cell Receptor Expression of RAG1 and RAG2 (Recombination Activating Genes) Recombination Heavy Chain Activating Genes Immunoglobulin Gene Rearrangement V1-50 D1-25 J1-6 C          TdT DNA Rearrangement of D and J TdT TdT Terminal Rearrangement of V deoxynucleotidyl transferase Heavy-chain primary RNA transcript RNA Heavy-chain messenger RNA