Introduction to Immunology PDF

Introduction to Immunology Angela Oest, MS, PA-C, MPH Center for Food Allergy & Asthma Research (CFAAR) Ann & Robert H. Lurie Children’s Hospital of Chicago Division of Allergy & Immunology Northwestern University Feinberg School of Medicine  Objectives Describe the differences between innate an...

Introduction to Immunology Angela Oest, MS, PA-C, MPH Center for Food Allergy & Asthma Research (CFAAR) Ann & Robert H. Lurie Children’s Hospital of Chicago Division of Allergy & Immunology Northwestern University Feinberg School of Medicine  Objectives Describe the differences between innate and adaptive immunity Describe the function of cytokines and the complement system in pathogen defense Understand how components of innate immunity interact with components of adaptive immunity to generate normal immune protection 8/13/23 2  What is Immunology? The study of how the body ("host") recognizes self from nonself ("pathogens") Goal: Kill the foreign matter without harming the host 8/13/23 3  Types of Pathogens Viruses Bacteria Fungi Parasites Viruses & bacteria: Most dominant infectious organisms in USA & industrialized world Parasites: Major cause of infections worldwide (I.e. Malaria) 8/13/23 4  Cells that Act in the Immune System  Lymphoid Organs Primary & Secondary Primary Lymphoid Organs – supply mature lymphocytes - Bone marrow – site of B cell maturation ("B" for bone marrow) - Thymus – site of T cell maturation ("T" for thymus) Secondary Lymphoid Organs – activate lymphocytes in a specific immune response - Lymph nodes (LN) - Spleen - Tonsils/adenoids - Lymphocyte accumulations in the gut, respiratory, genital and urinary tracts I.e. GALT (Gut Associated Lymphoid Tissue), BALT (Bronchial Associated Lymphoid Tissue) 8/13/23 6  The Immune System Two parts Innate Immune Response Adaptive Immune Response 8/13/23 7  Innate Immunity Adaptive Immunity Born with it Acquired through exposure Acts immediately Takes time Does not require activation Requires activation Nonspecific Specific – forms memory cells Recognizes carbohydrates & lipids on Recognizes proteins on foreign cells foreign cells Lymphocytes present in secondary Leukocytes circulate in the blood lymph organ 8/13/23 8 Innate Immune Response  Components of Innate Immunity Physical barriers – skin, epithelium, mucus membranes Chemical barriers – lysozyme, sweat, stomach acid Cellular components – Leukocytes – circulating in the blood Non-cellular components– Complement & Cytokines Inflammation – local response to infection or injury 8/13/23 10  Physical & Chemical Barriers Skin – very few microorganisms can penetrate intact skin Epithelium – gastrointestinal and respiratory system - Mucous membranes – sticky, traps and limits bacterial adhesion to epithelium - Hair, cilia – trap, sweep away particulate matter Lysozyme – enzyme that can lyse bacterial cell wall Found in tears, saliva, milk, mucus 8/13/23 11  Cellular Components (Leukocytes) Polymorphonuclear Granulocytes (PMNs) Neutrophils - Most numerous - Secrete chemicals: bleach & peroxide - Avid phagocytes - Elevated in bacterial infection Basophils - "basic loving" - Secrete histamine - Related to mast cells (in skin & mucus membranes) Eosinophils - "acid loving" - Parasite infections - Elevated in allergy 8/13/23 12  Cellular Components (Leukocytes) Macrophages - Derived from monocytes – after they pass from vessels into tissues - Found in large number where epithelium is in contact with external environment: skin, gastrointestinal & respiratory tract - Engulf particles by phagocytosis Dendritic cells – macrophage-like cells Both act as Antigen-presenting cells (APCs) - which activate the adaptive immune cells Recognize pathogens by pathogen-associated molecular patterns (PAMPs) 8/13/23 13  Cellular Components Natural Killer Cells - Lymphocyte- (which are generally more associated with the adaptive immune response) - Doesn't require activation – therefore included in the innate immune response - Major targets are virus-infected cells & cancer cells - Not antigen-specific – exact mechanism of recognition of targets is unknown 8/13/23 14  Non-cellular components - Cytokines Protein messengers released by cells of the immune system - Link parts of the immune system together by chemical communication - Often as a cascade – one cytokine stimulates the release of another Play a role in innate and adaptive immune responses Types - Interleukins (IL-1, IL-2, etc) - Interferons (IFN) - Chemokines - Lymphokines - Tumor Necrosis Factor (TNF) 8/13/23 15  Non-cellular components - Complement Complement – family of plasma proteins (30+ proteins, very complex) - A means of extracellular killing of microbes - Complement proteins synthesized in the liver and circulate in the blood - Triggered by infection or damage - 5 of the active proteins form a multiunit protein called membrane attack complex (MAC) Embeds itself in microbial plasma membrane Forms pore-like channels "punches holes" Membrane becomes leaky – kills microbe 8/13/23 16  Non-cellular components - Complement There are 2 main complement pathways: Classical complement pathway – Requires antibodies to activate the first complement protein (C1) Alternate complement pathway – Not antibody-dependent. Activated by carbohydrates on the surface of microbes and complement proteins beyond C1 Adapted from Understanding Pathophysiology. Mosby 2004 8/13/23 17  Inflammatory Response Nonspecific immune response to invasion by a pathogen (similar response to trauma, cold, heat injury) 1. Entry of bacteria into tissue – tissue injury causes release of chemicals 2. Vasodilation in the infected area – increased blood flow (warmth, redness, swelling) 3. Increased permeability of capillaries and venules 4. Chemotaxis – movement of leukocytes into interstitial fluid and tissue 5. Destruction of bacteria by phagocytosis or other mechanisms 8/13/23 18 Inflammatory Response Weebly.com 8/13/23 19 Adaptive Immune Response  Two Types of Adaptive Immune Responses Cell-mediated Immunity - Carried out by activated T cells that migrate to the site of infection - "Cells killing cells" Humoral-mediated Immunity - Carried out by activated B cells in secondary lymphoid organs that secrete antibodies into circulation - Humoral means body fluids 8/13/23 21  Components of Adaptive Immunity Cellular components - B lymphocytes (B cells) - CD19, CD20 – humoral-mediated immunity - T lymphocytes (T cells) - cell-mediated immunity Cytotoxic T cells (Tc, CD8) Helper T cells (Th, CD4) - Antigen-presenting cell required for activation 8/13/23 22  B Cell Receptors B cell receptor is an antibody on the surface Binds to a specific antigen like a lock and key 8/13/23 23  T Cell Receptors Do not directly recognize antigens Antigens are presented on major histocompatibility complexes (MHCs) - MHCs are unique to each person – genetic "identity tags" of self - Two classes Class I MHC – all nucleated cells (all cells except red blood cells) Class II MHC – only on the surface of macrophages, dendritic cells & B cells - T cell receptors can only recognize antigen if bound to MHC Cytotoxic T Cells (CD8) bind to Class I MHC Helper T Cells (CD4) bind to Class II MHC www.creativecommons.org 8/13/23 24  Human Leukocyte Antigen (HLA) Complexes Human version of the major histocompatibility complex Encoded by a cluster of genes on chromosome 6 Used to match for tissue transplantation to prevent rejection Certain HLA types are associated with specific autoimmune diseases Some HLA-mediated diseases may predispose to cancer 8/13/23 25 8/13/23 26  Details of Adaptive Immunity Th – Helper T cells - The "generals" - don't directly attack anything, but they begin and coordinate the immune response to a specific pathogen Enhance inflammation Stimulate cytotoxic T cells Stimulate B cells - Becomes activated by antigen-presenting cell – produces IL-2 - Two types: Th1 (cell-mediated) & Th2 (humoral) – usually in balance - IL-2 causes helper T cells to proliferate and differentiate into: Memory helper T cells – remembers the specific antigen for future exposure Effector helper T cells – coordinate the immune response specific to the antigen Produces IL-2 & IL-4 8/13/23 27  Details of Adaptive Immunity Tc – Cytotoxic T cells - Becomes activated by antigen presenting cell - IL-2 from helper T cell causes it to proliferate and differentiate into: Memory Cytotoxic T cells – remembers the specific antigen in case of future exposure Effector Cytotoxic T cells – "infantry of the army" – migrate to the site of infection and kill the pathogen itself or a virally infected cell - Cell-mediated immunity – "cells killing cells" 8/13/23 28  Details of Adaptive Immunity B cells - Becomes sensitized to antigen either by phagocytosis or antigen presenting cells - Receives signal from helper T cell via IL-4 – causes proliferation and differentiation into: Memory B cells - remembers the specific antigen in case of future exposure Plasma cells – remain in secondary lymphoid organs and become large secrete antibodies 8/13/23 29  How do Antibodies Destroy Pathogens? Antibodies – secreted by plasma cells into lymph and blood - Binds to the pathogen at the site of infection or in circulation - Leads to the destruction of pathogens in 3 ways: Neutralization – prevents virus or bacteria from binding to host cells Opsonization – tags a pathogen for destruction by phagocytes Complement activation – destroys pathogen by punching holes in the cell membrane 8/13/23 30  Immunoglobulins Family of proteins that includes B cell receptors and plasma cell antibodies Composed of 4 interlinked chains - 2 heavy chains (long chains) Stem is distinct for each Ig type - 2 light chains (short chains) Constant & variable regions 8/13/23 31  Immunoglobulin Classes Acronym: "MADGE" 5 classes: - IgM – first antibody produced after new infection (indicates recent infection), transient - IgG – most abundant, crosses placenta, long-term memory and active in secondary response to previous infection - IgE – involved in allergic reactions (found on mast cells & basophils) & parasite infections - IgA – mucosal immunity – found where body interacts with external environment – gastrointestinal, respiratory, genitourinary systems, secreted in breast milk - IgD- found in blood and lymph – actual function unknown 8/13/23 32 Antibody Titers with SARS-CoV-2 infection www.betterfamilyhealth.org 8/13/23 33  Vaccination to Induce Immunity Contain noninfectious antigens, derived from known pathogens, to generate a mild primary immune response Leads to immune memory – memory B cells, IgG When exposed to pathogen to which the host was vaccinated, the immune system mounts a quick and robust response 8/13/23 34  www.aai.org 8/13/23 35  Immunologic Testing Polymerase Chain Reaction (PCR) - detects genetic material from an organism or pathogen (I.e. virus) - Clinical application: SARS-Co-V2 testing Enzyme linked immunosorbent Assay (ELISA) - used to detect antibodies and other proteins in the blood - Clinical application: antibody titers, HIV diagnosis Western Blot – detects specific proteins in the blood - Clinical application: Lyme disease diagnosis (IgM and IgG band analysis) 8/13/23 36  Immunologic Testing Immunofluorescence – antibodies labeled with fluorescent dye and visualized under a microscope - Clinical application: diagnosis of auto-immune disease (I.e. lupus) - Level of auto-antibodies reported as a titer (1:160 considered clinically significant) Flow cytometry – a laser-based technique used to detect, identify and count cells in the blood, bone marrow or cerebral spinal fluid - Clinical application: I.e. diagnosis of leukemia & lymphoma 8/13/23 37 Questions?